Antioxidants

21 pages, 2276 KiB

Open AccessEditor’s ChoiceArticle

Impact of Combined Heat and Salt Stresses on Tomato Plants—Insights into Nutrient Uptake and Redox Homeostasis

by Bruno Sousa, Francisca Rodrigues, Cristiano Soares, Maria Martins, Manuel Azenha, Teresa Lino-Neto, Conceição Santos, Ana Cunha and Fernanda Fidalgo

Antioxidants 2022, 11(3), 478; https://doi.org/10.3390/antiox11030478 - 28 Feb 2022

Cited by 16 | Viewed by 3473

Abstract

Currently, salinity and heat are two critical threats to crop production and food security which are being aggravated by the global climatic instability. In this scenario, it is imperative to understand plant responses to simultaneous exposure to different stressors and the cross-talk between [...] Read more.

Currently, salinity and heat are two critical threats to crop production and food security which are being aggravated by the global climatic instability. In this scenario, it is imperative to understand plant responses to simultaneous exposure to different stressors and the cross-talk between underlying functional mechanisms. Thus, in this study, the physiological and biochemical responses of tomato plants (Solanum lycopersicum L.) to the combination of salinity (100 mM NaCl) and heat (42 °C; 4 h/day) stress were evaluated. After 21 days of co-exposure, the accumulation of Na⁺ in plant tissues was superior when salt-treated plants were also exposed to high temperatures compared to the individual saline treatment, leading to the depletion of other nutrients and a harsher negative effect on plant growth. Despite that, neither oxidative damage nor a major accumulation of reactive oxygen species took place under stress conditions, mostly due to the accumulation of antioxidant (AOX) metabolites alongside the activation of several AOX enzymes. Nonetheless, the plausible allocation of resources towards the defense pathways related to oxidative and osmotic stress, along with severe Na toxicity, heavily compromised the ability of plants to grow properly when the combination of salinity and heat was imposed. Full article

(This article belongs to the Special Issue Antioxidant Mechanisms in Plants)

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21 pages, 3527 KiB

Open AccessEditor’s ChoiceArticle

Bioactive Compounds and Antioxidant Activities in Different Fractions of Mango Fruits (Mangifera indica L., Cultivar Tommy Atkins and Keitt)

by Marcello Salvatore Lenucci, Riccardo Tornese, Giovanni Mita and Miriana Durante

Antioxidants 2022, 11(3), 484; https://doi.org/10.3390/antiox11030484 - 28 Feb 2022

Cited by 24 | Viewed by 6961

Abstract

This study aims to describe and compare the distribution of bioactive compounds, the fatty acids profiles, and the TEAC hydrophilic and lipophilic antioxidant activities in different fruit fractions (pulp, peel, and kernel) of two mango cultivars (Tommy Atkins and Keitt). All fractions are [...] Read more.

This study aims to describe and compare the distribution of bioactive compounds, the fatty acids profiles, and the TEAC hydrophilic and lipophilic antioxidant activities in different fruit fractions (pulp, peel, and kernel) of two mango cultivars (Tommy Atkins and Keitt). All fractions are sources of health-promoting bioactive compounds. Regardless of cultivars, pulp had the highest content of phytosterols (~150 mg/100 g dw), peels ranked first for pentaciclic triterpenes (from 14.2 to 17.7 mg/100 g dw), tocopherols, carotenoids, and chlorophylls, and kernels for phenolic compounds (from 421.6 to 1464.8 mg/100 g dw), flavonoids, condensed tannins, as well as hydrophilic and lipophilic antioxidant activities. Differences between the two cultivars were evidenced for ascorbic acid, which showed the highest levels in the peels and kernels of Keitt and Tommy Atkins fruits, respectively. Similarly, the concentration of dehydroascorbic acid was higher in the pulp of Tommy Atkins than Keitt. The highest percentage of saturated fatty acids was observed in pulp (~42%) and kernels (~50%), monounsaturated fatty acids in kernels (up to 41%), and polyunsaturated fatty acids in peels (up to 52%). Our results add information to the current knowledge on nutraceuticals’ distribution in different fractions of mango fruit, supporting its consumption as a healthy fruit and suggesting the great potential value of peels and kernels as sources of novel ingredients. Indeed, mango by-products generated during agronomic-to-industrial processing not only causes a significant environmental impact, but economic losses too. In this scenario, boosting research on conventional recovery methods offers eco-friendly solutions. However, green, novel biorefinery technologies may offer eco-friendly and profitable solutions, allowing the recovery of several more profitable by-products, sustaining their continuous growth since many bioactive compounds can be recovered from mango by-products that are potentially useful in the design of innovative nutraceutical, cosmeceutical, and pharmaceutical formulations. Full article

(This article belongs to the Special Issue Advances in Natural Antioxidants for Food Improvement)

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14 pages, 1930 KiB

Open AccessEditor’s ChoiceArticle

N-Acetylcysteine Inhibits Platelet Function through the Regeneration of the Non-Oxidative Form of Albumin

by Sonia Eligini, Benedetta Porro, Giancarlo Aldini, Susanna Colli and Cristina Banfi

Antioxidants 2022, 11(3), 445; https://doi.org/10.3390/antiox11030445 - 23 Feb 2022

Cited by 8 | Viewed by 3108

Abstract

N-acetylcysteine (NAC) is able to break down protein disulfides, generating free thiols. This mechanism occurs on mixed disulfides of albumin (HSA) to form mercaptoalbumin (HMA), the main antioxidant species in the plasma. Circulating HSA exists in two main forms: the reduced form [...] Read more.

N-acetylcysteine (NAC) is able to break down protein disulfides, generating free thiols. This mechanism occurs on mixed disulfides of albumin (HSA) to form mercaptoalbumin (HMA), the main antioxidant species in the plasma. Circulating HSA exists in two main forms: the reduced form (HMA), and the oxidized forms, whose predominant modification is cystenylation (HSA-Cys). Increased levels of oxidized HSA have been detected in several diseases associated with oxidative stress. This study showed that NAC inhibits platelet aggregation by restoring HMA. In addition, the regeneration of HMA by NAC inhibits platelet functions such as intracellular calcium mobilization, reactive oxygen species generation, arachidonic acid metabolites synthesis, and adhesion to the collagen matrix. In our conditions, the exposure of platelets to NAC did not increase GSH levels. However, the inhibition of platelet aggregation was also detected following treatment of platelet-rich plasma with GSH, which, similarly to NAC, reduced HSA-Cys levels. Furthermore, this study showed that cysteine, another compound able to restore HMA by reducing the HSA-Cys content, inhibited platelet aggregation to a similar extent as NAC. The results obtained in this study suggest a new mechanism by which NAC can modulate platelet activation and suggest its possible use as an antiplatelet drug in conditions associated with oxidative stress. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cardiovascular Diseases II)

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27 pages, 2362 KiB

Open AccessEditor’s ChoiceReview

Recent Progress in Antioxidant Active Substances from Marine Biota

by Todorka Vladkova, Nelly Georgieva, Anna Staneva and Dilyana Gospodinova

Antioxidants 2022, 11(3), 439; https://doi.org/10.3390/antiox11030439 - 22 Feb 2022

Cited by 16 | Viewed by 3803

Abstract

Background: The well-recognized but not fully explored antioxidant activity of marine-biota-derived, biologically active substances has led to interest in their study as substitutes of antibiotics, antiaging agents, anticancer and antiviral drugs, and others. The aim of this review is to present the current [...] Read more.

Background: The well-recognized but not fully explored antioxidant activity of marine-biota-derived, biologically active substances has led to interest in their study as substitutes of antibiotics, antiaging agents, anticancer and antiviral drugs, and others. The aim of this review is to present the current state of the art of marine-biota-derived antioxidants to give some ideas for potential industrial applications. Methods: This review is an update for the last 5 years on the marine sources of natural antioxidants, different classes antioxidant compounds, and current derivation biotechnologies. Results: New marine sources of antioxidants, including byproducts and wastes, are presented, along with new antioxidant substances and derivation approaches. Conclusions: The interest in high-value antioxidants from marine biota continues. Natural substances combining antioxidant and antimicrobial action are of particular interest because of the increasing microbial resistance to antibiotic treatments. New antioxidant substances are discovered, along with those extracted from marine biota collected in other locations. Byproducts and wastes provide a valuable source of antioxidant substances. The application of optimized non-conventional derivation approaches is expected to allow the intensification of the production and improvement in the quality of the derived substances. The ability to obtain safe, high-value products is of key importance for potential industrialization. Full article

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23 pages, 22379 KiB

Open AccessEditor’s ChoiceReview

The Effects of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (Nrf2) Activation in Preclinical Models of Peripheral Neuropathic Pain

by Paramita Basu, Dayna L. Averitt, Camelia Maier and Arpita Basu

Antioxidants 2022, 11(2), 430; https://doi.org/10.3390/antiox11020430 - 21 Feb 2022

Cited by 21 | Viewed by 4654

Abstract

Oxidative stress, resulting from an imbalance between the formation of damaging free radicals and availability of protective antioxidants, can contribute to peripheral neuropathic pain conditions. Reactive oxygen and nitrogen species, as well as products of the mitochondrial metabolism such as superoxide anions, hydrogen [...] Read more.

Oxidative stress, resulting from an imbalance between the formation of damaging free radicals and availability of protective antioxidants, can contribute to peripheral neuropathic pain conditions. Reactive oxygen and nitrogen species, as well as products of the mitochondrial metabolism such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, are common free radicals. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is a transcription factor encoded by the NFE2L2 gene and is a member of the cap ‘n’ collar subfamily of basic region leucine zipper transcription factors. Under normal physiological conditions, Nrf2 remains bound to Kelch-like ECH-associated protein 1 in the cytoplasm that ultimately leads to proteasomal degradation. During peripheral neuropathy, Nrf2 can translocate to the nucleus, where it heterodimerizes with muscle aponeurosis fibromatosis proteins and binds to antioxidant response elements (AREs). It is becoming increasingly clear that the Nrf2 interaction with ARE leads to the transcription of several antioxidative enzymes that can ameliorate neuropathy and neuropathic pain in rodent models. Current evidence indicates that the antinociceptive effects of Nrf2 occur via reducing oxidative stress, neuroinflammation, and mitochondrial dysfunction. Here, we will summarize the preclinical evidence supporting the role of Nrf2 signaling pathways and Nrf2 inducers in alleviating peripheral neuropathic pain. Full article

(This article belongs to the Special Issue Antioxidants in Chronic Pain II)

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36 pages, 2502 KiB

Open AccessEditor’s ChoiceReview

Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation

by Anushruti Ashok, Syed Suhail Andrabi, Saffar Mansoor, Youzhi Kuang, Brian K. Kwon and Vinod Labhasetwar

Antioxidants 2022, 11(2), 408; https://doi.org/10.3390/antiox11020408 - 17 Feb 2022

Cited by 57 | Viewed by 10306

Abstract

Free radicals are formed as a part of normal metabolic activities but are neutralized by the endogenous antioxidants present in cells/tissue, thus maintaining the redox balance. This redox balance is disrupted in certain neuropathophysiological conditions, causing oxidative stress, which is implicated in several [...] Read more.

Free radicals are formed as a part of normal metabolic activities but are neutralized by the endogenous antioxidants present in cells/tissue, thus maintaining the redox balance. This redox balance is disrupted in certain neuropathophysiological conditions, causing oxidative stress, which is implicated in several progressive neurodegenerative diseases. Following neuronal injury, secondary injury progression is also caused by excessive production of free radicals. Highly reactive free radicals, mainly the reactive oxygen species (ROS) and reactive nitrogen species (RNS), damage the cell membrane, proteins, and DNA, which triggers a self-propagating inflammatory cascade of degenerative events. Dysfunctional mitochondria under oxidative stress conditions are considered a key mediator in progressive neurodegeneration. Exogenous delivery of antioxidants holds promise to alleviate oxidative stress to regain the redox balance. In this regard, natural and synthetic antioxidants have been evaluated. Despite promising results in preclinical studies, clinical translation of antioxidants as a therapy to treat neurodegenerative diseases remains elusive. The issues could be their low bioavailability, instability, limited transport to the target tissue, and/or poor antioxidant capacity, requiring repeated and high dosing, which cannot be administered to humans because of dose-limiting toxicity. Our laboratory is investigating nanoparticle-mediated delivery of antioxidant enzymes to address some of the above issues. Apart from being endogenous, the main advantage of antioxidant enzymes is their catalytic mechanism of action; hence, they are significantly more effective at lower doses in detoxifying the deleterious effects of free radicals than nonenzymatic antioxidants. This review provides a comprehensive analysis of the potential of antioxidant therapy, challenges in their clinical translation, and the role nanoparticles/drug delivery systems could play in addressing these challenges. Full article

(This article belongs to the Special Issue Natural or Synthetic Antioxidants for Neurodegenerative Diseases and Brain Health)

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19 pages, 2828 KiB

Open AccessEditor’s ChoiceArticle

Bio-Waste Products of Mangifera indica L. Reduce Adipogenesis and Exert Antioxidant Effects on 3T3-L1 Cells

by Giovanni Pratelli, Daniela Carlisi, Antonella D’Anneo, Antonella Maggio, Sonia Emanuele, Antonio Palumbo Piccionello, Michela Giuliano, Anna De Blasio, Giuseppe Calvaruso and Marianna Lauricella

Antioxidants 2022, 11(2), 363; https://doi.org/10.3390/antiox11020363 - 11 Feb 2022

Cited by 17 | Viewed by 2501

Abstract

Several studies highlighted the beneficial value of natural compounds in the prevention and treatment of obesity. Here, we investigated the anti-obesity effects of extracts of peel and seed of mango (Mangifera indica L.) cultivated in Sicily (Italy) in 3T3-L1 cells. Mango Peel [...] Read more.

Several studies highlighted the beneficial value of natural compounds in the prevention and treatment of obesity. Here, we investigated the anti-obesity effects of extracts of peel and seed of mango (Mangifera indica L.) cultivated in Sicily (Italy) in 3T3-L1 cells. Mango Peel (MPE) and Mango Seed (MSE) extracts at a 100 µg/mL concentration significantly reduced lipid accumulation and triacylglycerol contents during 3T3-L1 adipocyte differentiation without toxicity. HPLC-ESI-MS analysis showed that both the extracts contain some polyphenolic compounds that can account for the observed biological effects. The anti-adipogenic effect of MPE and MSE was the result of down-regulation of the key adipogenic transcription factor PPARγ and its downstream targets FABP4/aP2, GLUT4 and Adipsin, as well SREBP-1c, a transcription factor which promotes lipogenesis. In addition, both MPE and MSE significantly activated AMPK with the consequent inhibition of Acetyl-CoA-carboxylase (ACC) and up-regulated PPARα. The addition of compound C, a specific AMPK inhibitor, reduced the effects of MPE and MSE on AMPK and ACC phosphorylation, suggesting a role of AMPK in mediating MPE and MSE anti-lipogenic effects. Notably, MPE and MSE possess an elevated radical scavenging activity, as demonstrated by DPPH radical scavenging assay, and reduced ROS content produced during adipocyte differentiation. This last effect could be a consequence of the increase in the antioxidant factors Nrf2, MnSOD and HO-1. In conclusion, MPE and MSE possesses both anti-adipogenic and antioxidant potential, thus suggesting that the bio-waste products of mango are promising anti-obesity natural compounds. Full article

(This article belongs to the Special Issue Agri-Food Wastes as Natural Source of Bioactive Antioxidants)

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22 pages, 1538 KiB

Open AccessEditor’s ChoiceReview

The Functional Interplay between Gut Microbiota, Protein Hydrolysates/Bioactive Peptides, and Obesity: A Critical Review on the Study Advances

by Simon Okomo Aloo and Deog-Hwan Oh

Antioxidants 2022, 11(2), 333; https://doi.org/10.3390/antiox11020333 - 08 Feb 2022

Cited by 12 | Viewed by 3418

Abstract

Diet is an essential factor determining the ratio of pathogenic and beneficial gut microbiota. Hydrolysates and bioactive peptides have been described as crucial ingredients from food protein that potentially impact human health beyond their roles as nutrients. These compounds can exert benefits in [...] Read more.

Diet is an essential factor determining the ratio of pathogenic and beneficial gut microbiota. Hydrolysates and bioactive peptides have been described as crucial ingredients from food protein that potentially impact human health beyond their roles as nutrients. These compounds can exert benefits in the body, including modulation of the gut microbiota, and thus, they can reduce metabolic disorders. This review summarized studies on the interaction between hydrolysates/peptides, gut microbes, and obesity, focusing on how hydrolysates/peptides influence gut microbiota composition and function that improve body weight. Findings revealed that gut microbes could exert anti-obesity effects by controlling the host’s energy balance and food intake. They also exhibit activity against obesity-induced inflammation by changing the expression of inflammatory-related transcription factors. Protein hydrolysates/peptides can suppress the growth of pro-obesity gut bacteria but facilitate the proliferation of those with anti-obesity effects. The compounds provide growth factors to the beneficial gut bacteria and also improve their resistance against extreme pH. Hydrolysates/peptides are good candidates to target obesity and obesity-related complications. Thus, they can allow the development of novel strategies to fight incidences of obesity. Future studies are needed to understand absorption fate, utilization by gut microbes, and stability of hydrolysates/peptides in the gut under obesity. Full article

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24 pages, 5355 KiB

Open AccessEditor’s ChoiceArticle

Anti-Obesity Effects of Ecklonia cava Extract in High-Fat Diet-Induced Obese Rats

by Muhammad Aleem Abbas, Naila Boby, Eon-Bee Lee, Joo-Heon Hong and Seung-Chun Park

Antioxidants 2022, 11(2), 310; https://doi.org/10.3390/antiox11020310 - 03 Feb 2022

Cited by 16 | Viewed by 3170

Abstract

Obesity is becoming a global epidemic as a result of high-calorie food intake and unhealthy lifestyles. Different marine plants, especially brown algae (Ecklonia cava), are traditionally used to treat different health-related issues. The study was carried out to investigate the anti-obesity [...] Read more.

Obesity is becoming a global epidemic as a result of high-calorie food intake and unhealthy lifestyles. Different marine plants, especially brown algae (Ecklonia cava), are traditionally used to treat different health-related issues. The study was carried out to investigate the anti-obesity properties of E. cava 70% ethanol extract. To evaluate the anti-obesity effect of E. cava, both in vitro and in vivo tests were performed. E. cava suppresses pre-adipocyte 3T3-L1 differentiation in a dose-dependent manner. In HFD-induced obese rats’ models, administration of E. cava 125, 250, and 500 mg/kg significantly decreases total body weight and organs, especially liver weight, in all treatment groups. Adipose tissue weight, including subcutaneous, epididymal, peritoneal, and mesenteric adipose tissue, was markedly reduced in E. cava-treated HFD rats in dose-dependent manners. In addition, liver-related biomarkers AST, ALP, ALT, and GGT were evaluated; the lower level of liver-related biomarkers indicates no liver injury or fatty liver issue in E. cava HFD treatment groups. In addition, E. cava treatment has significant effects on the expression of adipogenic and lipogenic (PPAR-γ, FAS, LPL, and SREBP-1c) genes. Altogether, these results show the anti-obesity effect of E. cava. We concluded that E. cava could be a potential candidate for the prevention of obesity-induced by a high-fat diet. Full article

(This article belongs to the Special Issue Oxidative Stress in Obesity)

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20 pages, 6221 KiB

Open AccessEditor’s ChoiceReview

Antiangiogenic Phytochemicals Constituent of Diet as Promising Candidates for Chemoprevention of Cancer

by Ana Dácil Marrero, Ana R. Quesada, Beatriz Martínez-Poveda and Miguel Ángel Medina

Antioxidants 2022, 11(2), 302; https://doi.org/10.3390/antiox11020302 - 31 Jan 2022

Cited by 19 | Viewed by 3846

Abstract

Despite the extensive knowledge on cancer nature acquired over the last years, the high incidence of this disease evidences a need for new approaches that complement the clinical intervention of tumors. Interestingly, many types of cancer are closely related to dietary habits associated [...] Read more.

Despite the extensive knowledge on cancer nature acquired over the last years, the high incidence of this disease evidences a need for new approaches that complement the clinical intervention of tumors. Interestingly, many types of cancer are closely related to dietary habits associated with the Western lifestyle, such as low fruit and vegetable intake. Recent advances around the old-conceived term of chemoprevention highlight the important role of phytochemicals as good candidates for the prevention or treatment of cancer. The potential to inhibit angiogenesis exhibited by many natural compounds constituent of plant foods makes them especially interesting for their use as chemopreventive agents. Here, we review the antitumoral potential, with a focus on the antiangiogenic effects, of phenolic and polyphenolic compounds, such as quercetin or myricetin; terpenoids, such as ursolic acid or kahweol; and anthraquinones from Aloe vera, in different in vitro and in vivo assays, and the available clinical data. Although clinical trials have failed to assess the preventive role of many of these compounds, encouraging preclinical data support the efficacy of phytochemicals constituent of diet in the prevention and treatment of cancer, but a deeper understanding of their mechanisms of action and better designed clinical trials are urgently needed. Full article

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40 pages, 2816 KiB

Open AccessEditor’s ChoiceReview

Up-To-Date Analysis of the Extraction Methods for Anthocyanins: Principles of the Techniques, Optimization, Technical Progress, and Industrial Application

by Noelia Tena and Agustin G. Asuero

Antioxidants 2022, 11(2), 286; https://doi.org/10.3390/antiox11020286 - 30 Jan 2022

Cited by 34 | Viewed by 7368

Abstract

Nowadays, food industries are concerned about satisfying legal requirements related to waste policy and environmental protection. In addition, they take steps to ensure food safety and quality products that have high nutritional properties. Anthocyanins are considered high added-value compounds due to their sensory [...] Read more.

Nowadays, food industries are concerned about satisfying legal requirements related to waste policy and environmental protection. In addition, they take steps to ensure food safety and quality products that have high nutritional properties. Anthocyanins are considered high added-value compounds due to their sensory qualities, colors, and nutritional properties; they are considered bioactive ingredients. They are found in high concentrations in many by-products across the food industry. Thus, the non-conventional extraction techniques presented here are useful in satisfying the current food industry requirements. However, selecting more convenient extraction techniques is not easy. Multiple factors are implicated in the decision. In this review, we compile the most recent applications (since 2015) used to extract anthocyanins from different natural matrices, via conventional and non-conventional extraction techniques. We analyze the main advantages and disadvantages of anthocyanin extraction techniques from different natural matrices and discuss the selection criteria for sustainability of the processes. We present an up-to-date analysis of the principles of the techniques and an optimization of the extraction conditions, technical progress, and industrial applications. Finally, we provide a critical comparison between these techniques and some recommendations, to select and optimize the techniques for industrial applications. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Anthocyanins and other Vegetal Pigments: Modern Assisted Extraction Methods and Analysis)

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20 pages, 6055 KiB

Open AccessEditor’s ChoiceArticle

Phenolic Content and Antioxidant Activity in Apples of the ‘Galaval’ Cultivar Grown on 17 Different Rootstocks

by Aurita Butkeviciute, Vytautas Abukauskas, Valdimaras Janulis and Darius Kviklys

Antioxidants 2022, 11(2), 266; https://doi.org/10.3390/antiox11020266 - 28 Jan 2022

Cited by 12 | Viewed by 3401

Abstract

Apple cultivars are one of the main factors setting the composition of bioactive compounds in apples and the quality of the fruit. However, research has been providing increasing amounts of data on the influence of rootstocks on the variations in the composition of [...] Read more.

Apple cultivars are one of the main factors setting the composition of bioactive compounds in apples and the quality of the fruit. However, research has been providing increasing amounts of data on the influence of rootstocks on the variations in the composition of bioactive compounds in apples. The aim of the study was to determine the influence of rootstocks on the changes in the qualitative and quantitative composition of phenolic compounds and their antioxidant activity in vitro in apple flesh and peel. HPLC analyses of phenolic compounds in apple samples were performed. The rootstock–scion combination had a significant effect on the composition and antioxidant activity of phenolic compounds in apple samples. Depending on the rootstock, the total content of phenolic compounds in apple flesh of the ‘Galaval’ cultivar could vary by 2.9 times, and in the peel by up to 90%. The genotype of the rootstock resulted in the highest variation in total flavan-3-ol content in apple flesh—by as much as 4.3 times—while the total content of flavonols varied by 2.1 times. In apple peel, on the contrary, the greatest variation was recorded for the total flavonol content (by 4.4 times), and the total flavan-3-ol content varied the least (by 1.8 times). A proper match of a cultivar and a rootstock can program a fruit tree to grow larger amounts of higher-quality, antioxidant-rich, and high-nutrition-value fruit. Full article

(This article belongs to the Special Issue Phenolics as Antioxidant Agents)

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38 pages, 1636 KiB

Open AccessEditor’s ChoiceReview

Naturally Occurring Antioxidant Therapy in Alzheimer’s Disease

by Andrila E. Collins, Tarek M. Saleh and Bettina E. Kalisch

Antioxidants 2022, 11(2), 213; https://doi.org/10.3390/antiox11020213 - 23 Jan 2022

Cited by 37 | Viewed by 7062

Abstract

It is estimated that the prevalence rate of Alzheimer’s disease (AD) will double by the year 2040. Although currently available treatments help with symptom management, they do not prevent, delay the progression of, or cure the disease. Interestingly, a shared characteristic of AD [...] Read more.

It is estimated that the prevalence rate of Alzheimer’s disease (AD) will double by the year 2040. Although currently available treatments help with symptom management, they do not prevent, delay the progression of, or cure the disease. Interestingly, a shared characteristic of AD and other neurodegenerative diseases and disorders is oxidative stress. Despite profound evidence supporting the role of oxidative stress in the pathogenesis and progression of AD, none of the currently available treatment options address oxidative stress. Recently, attention has been placed on the use of antioxidants to mitigate the effects of oxidative stress in the central nervous system. In preclinical studies utilizing cellular and animal models, natural antioxidants showed therapeutic promise when administered alone or in combination with other compounds. More recently, the concept of combination antioxidant therapy has been explored as a novel approach to preventing and treating neurodegenerative conditions that present with oxidative stress as a contributing factor. In this review, the relationship between oxidative stress and AD pathology and the neuroprotective role of natural antioxidants from natural sources are discussed. Additionally, the therapeutic potential of natural antioxidants as preventatives and/or treatment for AD is examined, with special attention paid to natural antioxidant combinations and conjugates that are currently being investigated in human clinical trials. Full article

(This article belongs to the Special Issue Antioxidants in Age-Related Diseases and Anti-Aging Strategies)

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24 pages, 2402 KiB

Open AccessEditor’s ChoiceReview

Reactive Oxygen Species (ROS) and Antioxidants as Immunomodulators in Exercise: Implications for Heme Oxygenase and Bilirubin

by David Travis Thomas, Nicholas R. DelCimmuto, Kyle D. Flack, David E. Stec and Terry D. Hinds, Jr.

Antioxidants 2022, 11(2), 179; https://doi.org/10.3390/antiox11020179 - 18 Jan 2022

Cited by 23 | Viewed by 4406

Abstract

Exercise is commonly prescribed as a lifestyle treatment for chronic metabolic diseases as it functions as an insulin sensitizer, cardio-protectant, and essential lifestyle tool for effective weight maintenance. Exercise boosts the production of reactive oxygen species (ROS) and subsequent transient oxidative damage, which [...] Read more.

Exercise is commonly prescribed as a lifestyle treatment for chronic metabolic diseases as it functions as an insulin sensitizer, cardio-protectant, and essential lifestyle tool for effective weight maintenance. Exercise boosts the production of reactive oxygen species (ROS) and subsequent transient oxidative damage, which also upregulates counterbalancing endogenous antioxidants to protect from ROS-induced damage and inflammation. Exercise elevates heme oxygenase-1 (HO-1) and biliverdin reductase A (BVRA) expression as built-in protective mechanisms, which produce the most potent antioxidant, bilirubin. Together, these mitigate inflammation and adiposity. Moderately raising plasma bilirubin protects in two ways: (1) via its antioxidant capacity to reduce ROS and inflammation, and (2) its newly defined function as a hormone that activates the nuclear receptor transcription factor PPARα. It is now understood that increasing plasma bilirubin can also drive metabolic adaptions, which improve deleterious outcomes of weight gain and obesity, such as inflammation, type II diabetes, and cardiovascular diseases. The main objective of this review is to describe the function of bilirubin as an antioxidant and metabolic hormone and how the HO-1–BVRA–bilirubin–PPARα axis influences inflammation, metabolic function and interacts with exercise to improve outcomes of weight management. Full article

(This article belongs to the Special Issue Heme Oxygenase (HO)-1 as an Immunoregulator in Health and Disease)

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24 pages, 947 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Strategies Targeting Mitochondrial Calcium Signaling: A New Hope for Neurological Diseases?

by Laura R. Rodríguez, Tamara Lapeña-Luzón, Noelia Benetó, Vicent Beltran-Beltran, Federico V. Pallardó, Pilar Gonzalez-Cabo and Juan Antonio Navarro

Antioxidants 2022, 11(1), 165; https://doi.org/10.3390/antiox11010165 - 15 Jan 2022

Cited by 18 | Viewed by 3689

Abstract

Calcium (Ca²⁺) is a versatile secondary messenger involved in the regulation of a plethora of different signaling pathways for cell maintenance. Specifically, intracellular Ca²⁺ homeostasis is mainly regulated by the endoplasmic reticulum and the mitochondria, whose Ca²⁺ exchange is [...] Read more.

Calcium (Ca²⁺) is a versatile secondary messenger involved in the regulation of a plethora of different signaling pathways for cell maintenance. Specifically, intracellular Ca²⁺ homeostasis is mainly regulated by the endoplasmic reticulum and the mitochondria, whose Ca²⁺ exchange is mediated by appositions, termed endoplasmic reticulum–mitochondria-associated membranes (MAMs), formed by proteins resident in both compartments. These tethers are essential to manage the mitochondrial Ca²⁺ influx that regulates the mitochondrial function of bioenergetics, mitochondrial dynamics, cell death, and oxidative stress. However, alterations of these pathways lead to the development of multiple human diseases, including neurological disorders, such as amyotrophic lateral sclerosis, Friedreich’s ataxia, and Charcot–Marie–Tooth. A common hallmark in these disorders is mitochondrial dysfunction, associated with abnormal mitochondrial Ca²⁺ handling that contributes to neurodegeneration. In this work, we highlight the importance of Ca²⁺ signaling in mitochondria and how the mechanism of communication in MAMs is pivotal for mitochondrial maintenance and cell homeostasis. Lately, we outstand potential targets located in MAMs by addressing different therapeutic strategies focused on restoring mitochondrial Ca²⁺ uptake as an emergent approach for neurological diseases. Full article

(This article belongs to the Special Issue Oxidative Stress, Calcium Dysregulation, and Mitochondrial Dysfunction in Human Diseases)

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22 pages, 4485 KiB

Open AccessEditor’s ChoiceArticle

by Razia Sultana Mohammad, Mustafa F. Lokhandwala and Anees A. Banday

Antioxidants 2022, 11(1), 156; https://doi.org/10.3390/antiox11010156 - 14 Jan 2022

Cited by 15 | Viewed by 2646

Abstract

Age is one of the major risk factors for the development of chronic pathologies, including kidney diseases. Oxidative stress and mitochondrial dysfunction play a pathogenic role in aging kidney disease. Transcription factor NRF2, a master regulator of redox homeostasis, is altered during aging, [...] Read more.

Age is one of the major risk factors for the development of chronic pathologies, including kidney diseases. Oxidative stress and mitochondrial dysfunction play a pathogenic role in aging kidney disease. Transcription factor NRF2, a master regulator of redox homeostasis, is altered during aging, but the exact implications of altered NRF2 signaling on age-related renal mitochondrial impairment are not yet clear. Herein, we investigated the role of sulforaphane, a well-known NRF2 activator, on age-related mitochondrial and kidney dysfunction. Young (2–4 month) and aged (20–24 month) male Fischer 344 rats were treated with sulforaphane (15 mg/kg body wt/day) in drinking water for four weeks. We observed significant impairment in renal cortical mitochondrial function along with perturbed redox homeostasis, decreased kidney function and marked impairment in NRF2 signaling in aged Fischer 344 rats. Sulforaphane significantly improved mitochondrial function and ameliorated kidney injury by increasing cortical NRF2 expression and activity and decreasing protein expression of KEAP1, an NRF2 repressor. Sulforaphane treatment did not affect the renal NRF2 expression or activity and mitochondrial function in young rats. Taken together, our results provide novel insights into the protective role of the NRF2 pathway in kidneys during aging and highlight the therapeutic potential of sulforaphane in mitigating kidney dysfunction in elders. Full article

(This article belongs to the Special Issue NRF2 in Health and Diseases)

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21 pages, 4962 KiB

Open AccessEditor’s ChoiceReview

Peroxide-Mediated Oxygenation of Organic Compounds by Fungal Peroxygenases

by Martin Hofrichter, Harald Kellner, Robert Herzog, Alexander Karich, Jan Kiebist, Katrin Scheibner and René Ullrich

Antioxidants 2022, 11(1), 163; https://doi.org/10.3390/antiox11010163 - 14 Jan 2022

Cited by 27 | Viewed by 4649

Abstract

Unspecific peroxygenases (UPOs), whose sequences can be found in the genomes of thousands of filamentous fungi, many yeasts and certain fungus-like protists, are fascinating biocatalysts that transfer peroxide-borne oxygen (from H₂O₂ or R-OOH) with high efficiency to a wide range [...] Read more.

Unspecific peroxygenases (UPOs), whose sequences can be found in the genomes of thousands of filamentous fungi, many yeasts and certain fungus-like protists, are fascinating biocatalysts that transfer peroxide-borne oxygen (from H₂O₂ or R-OOH) with high efficiency to a wide range of organic substrates, including less or unactivated carbons and heteroatoms. A twice-proline-flanked cysteine (PCP motif) typically ligates the heme that forms the heart of the active site of UPOs and enables various types of relevant oxygenation reactions (hydroxylation, epoxidation, subsequent dealkylations, deacylation, or aromatization) together with less specific one-electron oxidations (e.g., phenoxy radical formation). In consequence, the substrate portfolio of a UPO enzyme always combines prototypical monooxygenase and peroxidase activities. Here, we briefly review nearly 20 years of peroxygenase research, considering basic mechanistic, molecular, phylogenetic, and biotechnological aspects. Full article

(This article belongs to the Special Issue Dream Peroxygenases)

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27 pages, 6241 KiB

Open AccessEditor’s ChoiceArticle

Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways

by Miguel Rebollo-Hernanz, Yolanda Aguilera, Maria A. Martin-Cabrejas and Elvira Gonzalez de Mejia

Antioxidants 2022, 11(1), 136; https://doi.org/10.3390/antiox11010136 - 08 Jan 2022

Cited by 14 | Viewed by 3758

Abstract

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling [...] Read more.

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L⁻¹) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L⁻¹) and an aqueous extract (CAE, 100 µg mL⁻¹) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD. Full article

(This article belongs to the Special Issue Antioxidant Foods and Cardiometabolic Health)

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39 pages, 2768 KiB

Open AccessEditor’s ChoiceReview

Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies

by Elaine Luiza Santos Soares de Mendonça, Marilene Brandão Tenório Fragoso, Jerusa Maria de Oliveira, Jadriane Almeida Xavier, Marília Oliveira Fonseca Goulart and Alane Cabral Menezes de Oliveira

Antioxidants 2022, 11(1), 129; https://doi.org/10.3390/antiox11010129 - 07 Jan 2022

Cited by 32 | Viewed by 10592

Abstract

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may [...] Read more.

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem. Full article

(This article belongs to the Special Issue Oxidative Stress, Pregnancy and Pregnancy-Related Diseases)

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28 pages, 1804 KiB

Open AccessEditor’s ChoiceReview

Revisiting the Oxidation of Flavonoids: Loss, Conservation or Enhancement of Their Antioxidant Properties

by Hernan Speisky, Fereidoon Shahidi, Adriano Costa de Camargo and Jocelyn Fuentes

Antioxidants 2022, 11(1), 133; https://doi.org/10.3390/antiox11010133 - 07 Jan 2022

Cited by 79 | Viewed by 7073

Abstract

Flavonoids display a broad range of health-promoting bioactivities. Among these, their capacity to act as antioxidants has remained most prominent. The canonical reactive oxygen species (ROS)-scavenging mode of the antioxidant action of flavonoids relies on the high susceptibility of their phenolic moieties to [...] Read more.

Flavonoids display a broad range of health-promoting bioactivities. Among these, their capacity to act as antioxidants has remained most prominent. The canonical reactive oxygen species (ROS)-scavenging mode of the antioxidant action of flavonoids relies on the high susceptibility of their phenolic moieties to undergo oxidation. As a consequence, upon reaction with ROS, the antioxidant capacity of flavonoids is severely compromised. Other phenol-compromising reactions, such as those involved in the biotransformation of flavonoids, can also markedly affect their antioxidant properties. In recent years, however, increasing evidence has indicated that, at least for some flavonoids, the oxidation of such residues can in fact markedly enhance their original antioxidant properties. In such apparent paradoxical cases, the antioxidant activity arises from the pro-oxidant and/or electrophilic character of some of their oxidation-derived metabolites and is exerted by activating the Nrf2–Keap1 pathway, which upregulates the cell’s endogenous antioxidant capacity, and/or, by preventing the activation of the pro-oxidant and pro-inflammatory NF-κB pathway. This review focuses on the effects that the oxidative and/or non-oxidative modification of the phenolic groups of flavonoids may have on the ability of the resulting metabolites to promote direct and/or indirect antioxidant actions. Considering the case of a metabolite resulting from the oxidation of quercetin, we offer a comprehensive description of the evidence that increasingly supports the concept that, in the case of certain flavonoids, the oxidation of phenolics emerges as a mechanism that markedly amplifies their original antioxidant properties. An overlooked topic of great phytomedicine potential is thus unraveled. Full article

(This article belongs to the Topic Cellular Redox Homeostasis)

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15 pages, 2306 KiB

Open AccessEditor’s ChoiceArticle

Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice

by Guodong Zhou, Weiwu Jiang, Guobin Xia, Lihua Wang, Molly Richardson, Chun Chu and Bhagavatula Moorthy

Antioxidants 2022, 11(1), 119; https://doi.org/10.3390/antiox11010119 - 05 Jan 2022

Cited by 7 | Viewed by 2033

Abstract

Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which are constituents of [...] Read more.

Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which are constituents of fish oil (FO), significantly decreased DNA adduct formation by polycyclic aromatic hydrocarbons (PAHs). B6C3F1 male mice were fed an FO or corn oil (CO) diet, or A/J male mice were pre-fed with omega-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA). While the B6C3F1 mice were administered two doses of a mixture of seven carcinogenic PAHs including benzo(a)pyrene (BP), the A/J mice were treated i.p. with pure benzo[a]pyrene (BP). Animals were euthanized after 1, 3, or 7 d after PAH treatment. DNA adduct levels were measured by the ³²P-postlabeling assay. Our results showed that DNA adduct levels in the lungs of mice 7 d after treatment were significantly decreased in the FO or EPA/DHA groups compared with the CO group. Interestingly, both qPCR and Western blot analyses revealed that FO, DHA and EPA/DHA significantly decreased the expression of cytochrome P450 (CYP) 1B1. CYP1B1 plays a critical role in the metabolic activation of BP to DNA-reactive metabolites. qPCR also showed that the expression of some metabolic and DNA repair genes was induced by BP and inhibited by FO or omega-3 fatty acids in liver, but not lung. Our results suggest that a combination of mechanism entailing CYP1B1 inhibition and the modulation of DNA repair genes contribute to the attenuation of PAH-mediated carcinogenesis by omega 3 fatty acids. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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24 pages, 1531 KiB

Open AccessEditor’s ChoiceReview

Protein Oxidation in Muscle Foods: A Comprehensive Review

by Rubén Domínguez, Mirian Pateiro, Paulo E. S. Munekata, Wangang Zhang, Paula Garcia-Oliveira, Maria Carpena, Miguel A. Prieto, Benjamin Bohrer and José M. Lorenzo

Antioxidants 2022, 11(1), 60; https://doi.org/10.3390/antiox11010060 - 28 Dec 2021

Cited by 105 | Viewed by 9124

Abstract

Muscle foods and their products are a fundamental part of the human diet. The high protein content found in muscle foods, as well as the high content of essential amino acids, provides an appropriate composition to complete the nutritional requirements of humans. However, [...] Read more.

Muscle foods and their products are a fundamental part of the human diet. The high protein content found in muscle foods, as well as the high content of essential amino acids, provides an appropriate composition to complete the nutritional requirements of humans. However, due to their special composition, they are susceptible to oxidative degradation. In this sense, proteins are highly susceptible to oxidative reactions. However, in contrast to lipid oxidation, which has been studied in depth for decades, protein oxidation of muscle foods has been investigated much less. Moreover, these reactions have an important influence on the quality of muscle foods, from physico-chemical, techno-functional, and nutritional perspectives. In this regard, the loss of essential nutrients, the impairment of texture, water-holding capacity, color and flavor, and the formation of toxic substances are some of the direct consequences of protein oxidation. The loss of quality for muscle foods results in consumer rejection and substantial levels of economic losses, and thus the control of oxidative processes is of vital importance for the food industry. Nonetheless, the complexity of the reactions involved in protein oxidation and the many different factors that influence these reactions make the mechanisms of protein oxidation difficult to fully understand. Therefore, the present manuscript reviews the fundamental mechanisms of protein oxidation, the most important oxidative reactions, the main factors that influence protein oxidation, and the currently available analytical methods to quantify compounds derived from protein oxidation reactions. Finally, the main effects of protein oxidation on the quality of muscle foods, both from physico-chemical and nutritional points of view, are also discussed. Full article

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12 pages, 1739 KiB

Open AccessEditor’s ChoiceArticle

AGEs and sRAGE Variations at Different Timepoints in Patients with Chronic Kidney Disease

by Paolo Molinari, Lara Caldiroli, Elena Dozio, Roberta Rigolini, Paola Giubbilini, Massimiliano M. Corsi Romanelli, Piergiorgio Messa and Simone Vettoretti

Antioxidants 2021, 10(12), 1994; https://doi.org/10.3390/antiox10121994 - 15 Dec 2021

Cited by 10 | Viewed by 2451

Abstract

Patients with chronic kidney disease (CKD) are affected by enhanced oxidative stress and chronic inflammation, and these factors may contribute to increase advanced glycation end-products (AGEs). In this study we quantified AGEs and soluble receptors for AGE (sRAGE) isoforms and evaluated the association [...] Read more.

Patients with chronic kidney disease (CKD) are affected by enhanced oxidative stress and chronic inflammation, and these factors may contribute to increase advanced glycation end-products (AGEs). In this study we quantified AGEs and soluble receptors for AGE (sRAGE) isoforms and evaluated the association between their variations and eGFR at baseline and after 12 months. We evaluated 64 patients. AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer, and sRAGE by ELISA. Median age was 81 years, male patients accounted for 70%, 63% were diabetic, and eGFR was 27 ± 10 mL/min/1.73 m². At follow up, sRAGE isoforms underwent a significant decrement (1679 [1393;2038] vs. 1442 [1117;2102], p < 0.0001), while AGEs/sRAGE ratios were increased (1.77 ± 0.92 vs. 2.24 ± 1.34, p = 0.004). Although AGEs and AGEs/sRAGE ratios were inversely related with eGFR, their basal values as well their variations did not show a significant association with eGFR changes. In a cohort of patients with a stable clinical condition at 1 year follow-up, AGEs/sRAGE was associated with renal function. The lack of association with eGFR suggests that other factors can influence its increase. In conclusion, AGEs/sRAGE can be an additional risk factor for CKD progression over a longer time, but its role as a prognostic tool needs further investigation. Full article

(This article belongs to the Special Issue Antioxidants and Their Role in the Prevention and Treatment of Chronic Kidney Disease)

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21 pages, 5133 KiB

Open AccessEditor’s ChoiceArticle

Investigating the Drought and Salinity Effect on the Redox Components of Sulla coronaria (L.) Medik

by Silvia De Rossi, Gabriele Di Marco, Laura Bruno, Angelo Gismondi and Antonella Canini

Antioxidants 2021, 10(7), 1048; https://doi.org/10.3390/antiox10071048 - 29 Jun 2021

Cited by 26 | Viewed by 2179

Abstract

For the Mediterranean region, climate models predict an acceleration of desertification processes, thus threatening agriculture. The present work aimed to investigate the effect of drought and salinity on Sulla coronaria (L.) Medik., a Mediterranean forage legume, for understanding plant defence systems activated by [...] Read more.

For the Mediterranean region, climate models predict an acceleration of desertification processes, thus threatening agriculture. The present work aimed to investigate the effect of drought and salinity on Sulla coronaria (L.) Medik., a Mediterranean forage legume, for understanding plant defence systems activated by these stressors. In detail, we focused our attention on the variations on the plant redox status. Plants were subjected to suboptimal watering and irrigation with sodium chloride (NaCl) solutions. The same salt treatment was applied for in vitro tests on seedlings. Water content did not change after treatments. Salt negatively influenced seed germination and seedling development, but it did not affect photosynthesis parameters, contrary to what was observed in adult plants. Proline concentration increased in all samples, while abscisic acid level increased exclusively in seedlings. NaCl caused accumulation of superoxide anion in plants and seedlings and hydrogen peroxide only in seedlings; nevertheless, lipid peroxidation was not detected. Total phenolics, glutathione, expression level, and activity of antioxidant enzymes were assayed, revealing a complex antiradical molecular response, depending on the type of stress and development stage. Our results confirm Sulla as a drought- and salt-tolerant species and highlight its ability to counteract oxidative stress. This evidence suggests a key role for the redox components, as signal transduction messengers, in Sulla acclimation to desertification. Finally, plants and seedlings showed different acclimation capacity to salinity, revealing a greater genomic plasticity for seedlings. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Plants: Fine-Tuning of Their Production, Scavenging and Signaling Functions under Environmental Stress)

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25 pages, 1087 KiB

Open AccessEditor’s ChoiceReview

Mitophagy and Oxidative Stress: The Role of Aging

by Anna De Gaetano, Lara Gibellini, Giada Zanini, Milena Nasi, Andrea Cossarizza and Marcello Pinti

Antioxidants 2021, 10(5), 794; https://doi.org/10.3390/antiox10050794 - 17 May 2021

Cited by 59 | Viewed by 5948

Abstract

Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early responses to excessive reactive oxygen species [...] Read more.

Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early responses to excessive reactive oxygen species (ROS) production is the induction of mitophagy to remove damaged mitochondria. However, mitochondrial damage caused at least in part by chronic oxidative stress can accumulate, and autophagic and mitophagic pathways can become overwhelmed. The imbalance of the delicate equilibrium among mitophagy, ROS production and mitochondrial damage can start, drive, or accelerate the aging process, either in physiological aging, or in pathological age-related conditions, such as Alzheimer’s and Parkinson’s diseases. It remains to be determined which is the prime mover of this imbalance, i.e., whether it is the mitochondrial damage caused by ROS that initiates the dysregulation of mitophagy, thus activating a vicious circle that leads to the reduced ability to remove damaged mitochondria, or an alteration in the regulation of mitophagy leading to the excessive production of ROS by damaged mitochondria. Full article

(This article belongs to the Special Issue Regulation of Autophagy under Stress)

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19 pages, 6100 KiB

Open AccessEditor’s ChoiceArticle

Nitric Oxide Regulates Plant Growth, Physiology, Antioxidant Defense, and Ion Homeostasis to Confer Salt Tolerance in the Mangrove Species, Kandelia obovata

by Mirza Hasanuzzaman, Masashi Inafuku, Kamrun Nahar, Masayuki Fujita and Hirosuke Oku

Antioxidants 2021, 10(4), 611; https://doi.org/10.3390/antiox10040611 - 16 Apr 2021

Cited by 42 | Viewed by 3463

Abstract

Facultative halophyte Kandelia obovata plants were exposed to mild (1.5% NaCl) and severe (3% NaCl) salt stress with or without sodium nitroprusside (SNP; 100 µM; a NO donor), hemoglobin (Hb, 100 µM; a NO scavenger), or Nω-nitro-L-arginine methyl ester (L-NAME, 100 µM; a [...] Read more.

Facultative halophyte Kandelia obovata plants were exposed to mild (1.5% NaCl) and severe (3% NaCl) salt stress with or without sodium nitroprusside (SNP; 100 µM; a NO donor), hemoglobin (Hb, 100 µM; a NO scavenger), or Nω-nitro-L-arginine methyl ester (L-NAME, 100 µM; a NO synthase inhibitor). The plants were significantly affected by severe salt stress. They showed decreases in seedling growth, stomatal conductance, intercellular CO₂ concentration, SPAD value, photosynthetic rate, transpiration rate, water use efficiency, and disrupted antioxidant defense systems, overproduction of reactive oxygen species, and visible oxidative damage. Salt stress also induced ion toxicity and disrupted nutrient homeostasis, as indicated by elevated leaf and root Na⁺ contents, decreased K⁺ contents, lower K⁺/Na⁺ ratios, and decreased Ca contents while increasing osmolyte (proline) levels. Treatment of salt-stressed plants with SNP increased endogenous NO levels, reduced ion toxicity, and improved nutrient homeostasis while further increasing Pro levels to maintain osmotic balance. SNP treatment also improved gas exchange parameters and enhanced antioxidant enzymes’ activities (catalase, ascorbate peroxidase, monodehydroascorbate reductase, and dehydroascorbate reductase). Treatment with Hb and l-NAME reversed these beneficial SNP effects and exacerbated salt damage, confirming that SNP promoted stress recovery and improved plant growth under salt stress. Full article

(This article belongs to the Special Issue Approaches in Enhancing Antioxidant Defense in Plants)

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13 pages, 4349 KiB

Open AccessEditor’s ChoiceArticle

Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits

by Shin Koike, Kazuya Toriumi, Sakura Kasahara, Yosuke Kibune, Yo-ichi Ishida, Takashi Dan, Toshio Miyata, Makoto Arai and Yuki Ogasawara

Antioxidants 2021, 10(4), 574; https://doi.org/10.3390/antiox10040574 - 08 Apr 2021

Cited by 8 | Viewed by 2943

Abstract

Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl stress and the pathogenesis of this disease is not well established. In this study, glyoxalase 1(Glo1)-knockout and vitamin B6-deficient [...] Read more.

Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl stress and the pathogenesis of this disease is not well established. In this study, glyoxalase 1(Glo1)-knockout and vitamin B6-deficient mice (KO/VB6 (-) mice), which are susceptible to methylglyoxal (MGO)-induced oxidative damages, were used as a CS-SCZ model to analyze MGO-modified protein and the carbonyl stress status in the brain. A comparison between Wild/VB6(+) mice and KO/VB6(−) mice for accumulated carbonyl proteins levels, with several advanced glycation end products (AGEs) in the brain, revealed that carbonyl protein levels with the Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl) ornithine (MG-H1) moiety were significantly increased in the hippocampus, prefrontal cortex, striatum, cerebral cortex, and brainstem regions of the brain in KO/VB6(−) mice. Moreover, two-dimensional electrophoresis and Liquid chromatography-tandem mass spectrometry analysis showed MG-H1-modified arginine residues in mitochondrial creatine kinase, beta-adrenergic receptor kinase 1, and T-complex protein in the hippocampus region of KO/VB6(−) mice, but not in Wild/VB6(+) mice. In particular, MG-H1 modification of mitochondrial creatine kinase was quite notable. These results suggest that further studies focusing on MG-H1-modified and accumulated proteins in the hippocampus may reveal the onset mechanism of CS-SCZ induced by MGO-induced oxidative damages. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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17 pages, 2811 KiB

Open AccessEditor’s ChoiceArticle

Label-Free Quantitative Proteomic Analysis of Nitrogen Starvation in Arabidopsis Root Reveals New Aspects of H₂S Signaling by Protein Persulfidation

by Ana Jurado-Flores, Luis C. Romero and Cecilia Gotor

Antioxidants 2021, 10(4), 508; https://doi.org/10.3390/antiox10040508 - 24 Mar 2021

Cited by 33 | Viewed by 3700

Abstract

Hydrogen sulfide (H₂S)-mediated signaling pathways regulate many physiological and pathophysiological processes in mammalian and plant systems. The molecular mechanism by which hydrogen sulfide exerts its action involves the posttranslational modification of cysteine residues to form a persulfidated thiol motif. We developed [...] Read more.

Hydrogen sulfide (H₂S)-mediated signaling pathways regulate many physiological and pathophysiological processes in mammalian and plant systems. The molecular mechanism by which hydrogen sulfide exerts its action involves the posttranslational modification of cysteine residues to form a persulfidated thiol motif. We developed a comparative and label-free quantitative proteomic analysis approach for the detection of endogenous persulfidated proteins in N-starved Arabidopsis thaliana roots by using the tag-switch method. In this work, we identified 5214 unique proteins from root tissue that were persulfidated, 1674 of which were quantitatively analyzed and found to show altered persulfidation levels in vivo under N deprivation. These proteins represented almost 13% of the entire annotated proteome in Arabidopsis. Bioinformatic analysis revealed that persulfidated proteins were involved in a wide range of biological functions, regulating important processes such as primary metabolism, plant responses to stresses, growth and development, RNA translation and protein degradation. Quantitative mass spectrometry analysis allowed us to obtain a comprehensive view of hydrogen sulfide signaling via changes in the persulfidation levels of key protein targets involved in ubiquitin-dependent protein degradation and autophagy, among others. Full article

(This article belongs to the Special Issue Plant and Human Sulfur Biology)

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14 pages, 2550 KiB

Open AccessEditor’s ChoiceArticle

Allysine and α-Aminoadipic Acid as Markers of the Glyco-Oxidative Damage to Human Serum Albumin under Pathological Glucose Concentrations

by Carolina Luna, Alexis Arjona, Carmen Dueñas and Mario Estevez

Antioxidants 2021, 10(3), 474; https://doi.org/10.3390/antiox10030474 - 17 Mar 2021

Cited by 13 | Viewed by 2662

Abstract

Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such [...] Read more.

Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such as diabetes. Allysine as well as its oxidation product, the α-amino adipic acid (α-AA) have been found to be markers of diabetes risk whereas little is known about the chemistry involved in its formation under hyperglycemic conditions. To provide insight into this issue, human serum albumin was incubated in the presence of FeCl3 (25 μM) and increasing glucose concentrations for 32 h at 37 °C. These concentrations were selected to simulate (i) physiological fasting plasma concentration (4 mM), (ii) pathological pre-diabetes fasting plasma concentration (8 mM), and pathological diabetes fasting plasma concentration (12 mM) of glucose. While both allysine and α-AA were found to increase with increasing glucose concentrations, the carboxylic acid was only detected at pathological glucose concentrations and appeared to be a more reliable indicator of glyco-oxidative stress. The underlying chemical mechanisms of lysine glycation as well as of the depletion of tryptophan and formation of fluorescent and colored advanced glycation products are discussed. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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21 pages, 4352 KiB

Open AccessEditor’s ChoiceArticle

A Workflow towards the Reproducible Identification and Quantitation of Protein Carbonylation Sites in Human Plasma

by Juan Camilo Rojas Echeverri, Sanja Milkovska-Stamenova and Ralf Hoffmann

Antioxidants 2021, 10(3), 369; https://doi.org/10.3390/antiox10030369 - 01 Mar 2021

Cited by 12 | Viewed by 2875

Abstract

Protein carbonylation, a marker of excessive oxidative stress, has been studied in the context of multiple human diseases related to oxidative stress. The variety of post-translational carbonyl modifications (carbonyl PTMs) and their low concentrations in plasma challenge their reproducible identification and quantitation. However, [...] Read more.

Protein carbonylation, a marker of excessive oxidative stress, has been studied in the context of multiple human diseases related to oxidative stress. The variety of post-translational carbonyl modifications (carbonyl PTMs) and their low concentrations in plasma challenge their reproducible identification and quantitation. However, carbonyl-specific biotinylated derivatization tags (e.g., aldehyde reactive probe, ARP) allow for targeting carbonyl PTMs by enriching proteins and peptides carrying these modifications. In this study, an oxidized human serum albumin protein model (OxHSA) and plasma from a healthy donor were derivatized with ARP, digested with trypsin, and enriched using biotin-avidin affinity chromatography prior to nano reversed-phase chromatography coupled online to electrospray ionization tandem mass spectrometry with travelling wave ion mobility spectrometry (nRPC-ESI-MS/MS-TWIMS). The presented workflow addresses several analytical challenges by using ARP-specific fragment ions to reliably identify ARP peptides. Furthermore, the reproducible recovery and relative quantitation of ARP peptides were validated. Human serum albumin (HSA) in plasma was heavily modified by a variety of direct amino acid oxidation products and adducts from reactive carbonyl species (RCS), with most RCS modifications being detected in six hotspots, i.e., Lys10, Lys190, Lys199, Lys281, Lys432, and Lys525 of mature HSA. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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21 pages, 1863 KiB

Open AccessEditor’s ChoiceArticle

In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies

by Alessandra Altomare, Giovanna Baron, Marta Balbinot, Alma Martínez Fernández, Alessandro Pedretti, Beatrice Zoanni, Maura Brioschi, Piergiuseppe Agostoni, Marina Carini, Cristina Banfi and Giancarlo Aldini

Antioxidants 2021, 10(3), 358; https://doi.org/10.3390/antiox10030358 - 27 Feb 2021

Cited by 5 | Viewed by 3125

Abstract

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma [...] Read more.

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma AGEs/ALEs involved in HF (untargeted approach). This work provides the first ex vivo high-resolution mass spectrometry (HR-MS) profiling of AGEs/ALEs occurring in human serum albumin (HSA), the most abundant protein in plasma, characterized by several nucleophilic sites and thus representing the main protein substrate for AGE/ALE formation. A set of AGE/ALE adducts in pooled HF-HSA samples was defined, and a semi-quantitative analysis was carried out in order to finally select those presenting in increased amounts in the HF samples with respect to the control condition. These adducts were statistically confirmed by monitoring their content in individual HF samples by applying a targeted approach. Selected AGEs/ALEs proved to be mostly CML derivatives on Lys residues (i.e., CML-Lys12, CML-Lys378, CML-Lys402), and one deoxy-fructosyl derivative on the Lys 389 (DFK-Lys 389). The nature of CML adducts was finally confirmed using immunological methods and in vitro production of such adducts further confirmed by mass spectrometry. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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16 pages, 2754 KiB

Open AccessEditor’s ChoiceArticle

Selenium-Binding Protein 1 (SELENBP1) Supports Hydrogen Sulfide Biosynthesis and Adipogenesis

by Elisa B. Randi, Giovanna Casili, Simona Jacquemai and Csaba Szabo

Antioxidants 2021, 10(3), 361; https://doi.org/10.3390/antiox10030361 - 27 Feb 2021

Cited by 24 | Viewed by 3574

Abstract

Hydrogen sulfide (H₂S), a mammalian gasotransmitter, is involved in the regulation of a variety of fundamental processes including intracellular signaling, cellular bioenergetics, cell proliferation, and cell differentiation. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST) are currently considered the [...] Read more.

Hydrogen sulfide (H₂S), a mammalian gasotransmitter, is involved in the regulation of a variety of fundamental processes including intracellular signaling, cellular bioenergetics, cell proliferation, and cell differentiation. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST) are currently considered the three principal mammalian H₂S-generating enzymes. However, recently, a fourth H₂S-producing enzyme, selenium-binding-protein 1 (SELENBP1), has also been identified. The cellular regulatory role(s) of SELENBP1 are incompletely understood. The current study investigated whether SELENBP1 plays a role in the regulation of adipocyte differentiation in vitro. 3T3-L1 preadipocytes with or without SELENBP1 knock-down were subjected to differentiation-inducing conditions, and H₂S production, cellular lipid accumulation, cell proliferation, and mitochondrial activity were quantified. Adipocyte differentiation was associated with an upregulation of H₂S biosynthesis. SELENBP1 silencing decreased cellular H₂S levels, suppressed the expression of the three “classical” H₂S-producing enzymes (CBS, CSE, and 3-MST) and significantly suppressed adipocyte differentiation. Treatment of SELENBP1 knock-down cells with the H₂S donor GYY4137 partially restored lipid accumulation, increased cellular H₂S levels, and exerted a bell-shaped effect on cellular bioenergetics (enhancement at 1 and 3 mM, and inhibition at 6 mM). We conclude that SELENBP1 in adipocytes (1) contributes to H₂S biosynthesis and (2) acts as an endogenous stimulator of adipocyte differentiation. Full article

(This article belongs to the Special Issue Hydrogen Sulfide in Biology)

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39 pages, 3901 KiB

Open AccessEditor’s ChoiceReview

Functions of ROS in Macrophages and Antimicrobial Immunity

by Marc Herb and Michael Schramm

Antioxidants 2021, 10(2), 313; https://doi.org/10.3390/antiox10020313 - 19 Feb 2021

Cited by 234 | Viewed by 27279

Abstract

Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS [...] Read more.

Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review, we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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37 pages, 4137 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Abiotic Stress and Reactive Oxygen Species: Generation, Signaling, and Defense Mechanisms

by Swati Sachdev, Shamim Akhtar Ansari, Mohammad Israil Ansari, Masayuki Fujita and Mirza Hasanuzzaman

Antioxidants 2021, 10(2), 277; https://doi.org/10.3390/antiox10020277 - 11 Feb 2021

Cited by 424 | Viewed by 18139

Abstract

Climate change is an invisible, silent killer with calamitous effects on living organisms. As the sessile organism, plants experience a diverse array of abiotic stresses during ontogenesis. The relentless climatic changes amplify the intensity and duration of stresses, making plants dwindle to survive. [...] Read more.

Climate change is an invisible, silent killer with calamitous effects on living organisms. As the sessile organism, plants experience a diverse array of abiotic stresses during ontogenesis. The relentless climatic changes amplify the intensity and duration of stresses, making plants dwindle to survive. Plants convert 1–2% of consumed oxygen into reactive oxygen species (ROS), in particular, singlet oxygen (¹O₂), superoxide radical (O₂^•–), hydrogen peroxide (H₂O₂), hydroxyl radical (^•OH), etc. as a byproduct of aerobic metabolism in different cell organelles such as chloroplast, mitochondria, etc. The regulatory network comprising enzymatic and non-enzymatic antioxidant systems tends to keep the magnitude of ROS within plant cells to a non-damaging level. However, under stress conditions, the production rate of ROS increases exponentially, exceeding the potential of antioxidant scavengers instigating oxidative burst, which affects biomolecules and disturbs cellular redox homeostasis. ROS are similar to a double-edged sword; and, when present below the threshold level, mediate redox signaling pathways that actuate plant growth, development, and acclimatization against stresses. The production of ROS in plant cells displays both detrimental and beneficial effects. However, exact pathways of ROS mediated stress alleviation are yet to be fully elucidated. Therefore, the review deposits information about the status of known sites of production, signaling mechanisms/pathways, effects, and management of ROS within plant cells under stress. In addition, the role played by advancement in modern techniques such as molecular priming, systems biology, phenomics, and crop modeling in preventing oxidative stress, as well as diverting ROS into signaling pathways has been canvassed. Full article

(This article belongs to the Special Issue Approaches in Enhancing Antioxidant Defense in Plants)

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14 pages, 3388 KiB

Open AccessEditor’s ChoiceArticle

Overexpression of the Golden SNP-Carrying Orange Gene Enhances Carotenoid Accumulation and Heat Stress Tolerance in Sweetpotato Plants

by So-Eun Kim, Chan-Ju Lee, Sul-U Park, Ye-Hoon Lim, Woo Sung Park, Hye-Jin Kim, Mi-Jeong Ahn, Sang-Soo Kwak and Ho Soo Kim

Antioxidants 2021, 10(1), 51; https://doi.org/10.3390/antiox10010051 - 04 Jan 2021

Cited by 29 | Viewed by 3704

Abstract

Carotenoids function as photosynthetic accessory pigments, antioxidants, and vitamin A precursors. We recently showed that transgenic sweetpotato calli overexpressing the mutant sweetpotato (Ipomoea batatas [L.] Lam) Orange gene (IbOr-R96H), which carries a single nucleotide polymorphism responsible for Arg [...] Read more.

Carotenoids function as photosynthetic accessory pigments, antioxidants, and vitamin A precursors. We recently showed that transgenic sweetpotato calli overexpressing the mutant sweetpotato (Ipomoea batatas [L.] Lam) Orange gene (IbOr-R96H), which carries a single nucleotide polymorphism responsible for Arg to His substitution at amino acid position 96, exhibited dramatically higher carotenoid content and abiotic stress tolerance than calli overexpressing the wild-type IbOr gene (IbOr-WT). In this study, we generated transgenic sweetpotato plants overexpressing IbOr-R96H under the control of the cauliflower mosaic virus (CaMV) 35S promoter via Agrobacterium-mediated transformation. The total carotenoid contents of IbOr-R96H storage roots (light-orange flesh) and IbOr-WT storage roots (light-yellow flesh) were 5.4–19.6 and 3.2-fold higher, respectively, than those of non-transgenic (NT) storage roots (white flesh). The β-carotene content of IbOr-R96H storage roots was up to 186.2-fold higher than that of NT storage roots. In addition, IbOr-R96H plants showed greater tolerance to heat stress (47 °C) than NT and IbOr-WT plants, possibly because of higher DPPH radical scavenging activity and ABA contents. These results indicate that IbOr-R96H is a promising strategy for developing new sweetpotato cultivars with improved carotenoid contents and heat stress tolerance. Full article

(This article belongs to the Special Issue Antioxidant Defenses in Plants)

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25 pages, 1189 KiB

Open AccessEditor’s ChoiceReview

Oxidative Stress and Antioxidant Treatments in Cardiovascular Diseases

by Wenjun Wang and Peter M. Kang

Antioxidants 2020, 9(12), 1292; https://doi.org/10.3390/antiox9121292 - 17 Dec 2020

Cited by 83 | Viewed by 8483

Abstract

Oxidative stress plays a key role in many physiological and pathological conditions. The intracellular oxidative homeostasis is tightly regulated by the reactive oxygen species production and the intracellular defense mechanisms. Increased oxidative stress could alter lipid, DNA, and protein, resulting in cellular inflammation [...] Read more.

Oxidative stress plays a key role in many physiological and pathological conditions. The intracellular oxidative homeostasis is tightly regulated by the reactive oxygen species production and the intracellular defense mechanisms. Increased oxidative stress could alter lipid, DNA, and protein, resulting in cellular inflammation and programmed cell death. Evidences show that oxidative stress plays an important role in the progression of various cardiovascular diseases, such as atherosclerosis, heart failure, cardiac arrhythmia, and ischemia-reperfusion injury. There are a number of therapeutic options to treat oxidative stress-associated cardiovascular diseases. Well known antioxidants, such as nutritional supplements, as well as more novel antioxidants have been studied. In addition, novel therapeutic strategies using miRNA and nanomedicine are also being developed to treat various cardiovascular diseases. In this article, we provide a detailed description of oxidative stress. Then, we will introduce the relationship between oxidative stress and several cardiovascular diseases. Finally, we will focus on the clinical implications of oxidative stress in cardiovascular diseases. Full article

(This article belongs to the Special Issue Oxidative stress and Applied Biology)

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13 pages, 2722 KiB

Open AccessEditor’s ChoiceArticle

Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

by Amy K. Hauck, Tong Zhou, Ambuj Upadhyay, Yuxiang Sun, Michael B. O’Connor, Yue Chen and David A. Bernlohr

Antioxidants 2020, 9(12), 1210; https://doi.org/10.3390/antiox9121210 - 01 Dec 2020

Cited by 13 | Viewed by 2615

Abstract

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and [...] Read more.

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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20 pages, 775 KiB

Open AccessEditor’s ChoiceReview

The Advanced Lipoxidation End-Product Malondialdehyde-Lysine in Aging and Longevity

by Mariona Jové, Natàlia Mota-Martorell, Irene Pradas, Meritxell Martín-Gari, Victoria Ayala and Reinald Pamplona

Antioxidants 2020, 9(11), 1132; https://doi.org/10.3390/antiox9111132 - 15 Nov 2020

Cited by 51 | Viewed by 5509

Abstract

The nonenzymatic adduction of malondialdehyde (MDA) to the protein amino groups leads to the formation of malondialdehyde-lysine (MDALys). The degree of unsaturation of biological membranes and the intracellular oxidative conditions are the main factors that modulate MDALys formation. The low concentration of this [...] Read more.

The nonenzymatic adduction of malondialdehyde (MDA) to the protein amino groups leads to the formation of malondialdehyde-lysine (MDALys). The degree of unsaturation of biological membranes and the intracellular oxidative conditions are the main factors that modulate MDALys formation. The low concentration of this modification in the different cellular components, found in a wide diversity of tissues and animal species, is indicative of the presence of a complex network of cellular protection mechanisms that avoid its cytotoxic effects. In this review, we will focus on the chemistry of this lipoxidation-derived protein modification, the specificity of MDALys formation in proteins, the methodology used for its detection and quantification, the MDA-lipoxidized proteome, the metabolism of MDA-modified proteins, and the detrimental effects of this protein modification. We also propose that MDALys is an indicator of the rate of aging based on findings which demonstrate that (i) MDALys accumulates in tissues with age, (ii) the lower the concentration of MDALys the greater the longevity of the animal species, and (iii) its concentration is attenuated by anti-aging nutritional and pharmacological interventions. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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18 pages, 1844 KiB

Open AccessEditor’s ChoiceReview

Are Flavonoids Effective Antioxidants in Plants? Twenty Years of Our Investigation

by Giovanni Agati, Cecilia Brunetti, Alessio Fini, Antonella Gori, Lucia Guidi, Marco Landi, Federico Sebastiani and Massimiliano Tattini

Antioxidants 2020, 9(11), 1098; https://doi.org/10.3390/antiox9111098 - 09 Nov 2020

Cited by 127 | Viewed by 7551

Abstract

Whether flavonoids play significant antioxidant roles in plants challenged by photooxidative stress of different origin has been largely debated over the last few decades. A critical review of the pertinent literature and our experimentation as well, based on a free-of-scale approach, support an [...] Read more.

Whether flavonoids play significant antioxidant roles in plants challenged by photooxidative stress of different origin has been largely debated over the last few decades. A critical review of the pertinent literature and our experimentation as well, based on a free-of-scale approach, support an important antioxidant function served by flavonoids in plants exposed to a wide range of environmental stressors, the significance of which increases with the severity of stress. On the other side, some questions need conclusive answers when the putative antioxidant functions of plant flavonoids are examined at the level of both the whole-cell and cellular organelles. This partly depends upon a conclusive, robust, and unbiased definition of “a plant antioxidant”, which is still missing, and the need of considering the subcellular re-organization that occurs in plant cells in response to severe stress conditions. This likely makes our deterministic-based approach unsuitable to unveil the relevance of flavonoids as antioxidants in extremely complex biological systems, such as a plant cell exposed to an ever-changing stressful environment. This still poses open questions about how to measure the occurred antioxidant action of flavonoids. Our reasoning also evidences the need of contemporarily evaluating the changes in key primary and secondary components of the antioxidant defense network imposed by stress events of increasing severity to properly estimate the relevance of the antioxidant functions of flavonoids in an in planta situation. In turn, this calls for an in-depth analysis of the sub-cellular distribution of primary and secondary antioxidants to solve this still intricate matter. Full article

(This article belongs to the Special Issue Antioxidant Defenses in Plants)

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23 pages, 1991 KiB

Open AccessEditor’s ChoiceReview

ROS and NO Regulation by Melatonin Under Abiotic Stress in Plants

by Miriam Pardo-Hernández, Maria López-Delacalle and Rosa M. Rivero

Antioxidants 2020, 9(11), 1078; https://doi.org/10.3390/antiox9111078 - 03 Nov 2020

Cited by 79 | Viewed by 5719

Abstract

Abiotic stress in plants is an increasingly common problem in agriculture, and thus, studies on plant treatments with specific compounds that may help to mitigate these effects have increased in recent years. Melatonin (MET) application and its role in mitigating the negative effects [...] Read more.

Abiotic stress in plants is an increasingly common problem in agriculture, and thus, studies on plant treatments with specific compounds that may help to mitigate these effects have increased in recent years. Melatonin (MET) application and its role in mitigating the negative effects of abiotic stress in plants have become important in the last few years. MET, a derivative of tryptophan, is an important plant-related response molecule involved in the growth, development, and reproduction of plants, and the induction of different stress factors. In addition, MET plays a protective role against different abiotic stresses such as salinity, high/low temperature, high light, waterlogging, nutrient deficiency and stress combination by regulating both the enzymatic and non-enzymatic antioxidant defense systems. Moreover, MET interacts with many signaling molecules, such as reactive oxygen species (ROS) and nitric oxide (NO), and participates in a wide variety of physiological reactions. It is well known that NO produces S-nitrosylation and NO₂-Tyr of important antioxidant-related proteins, with this being an important mechanism for maintaining the antioxidant capacity of the AsA/GSH cycle under nitro-oxidative conditions, as extensively reviewed here under different abiotic stress conditions. Lastly, in this review, we show the coordinated actions between NO and MET as a long-range signaling molecule, regulating many responses in plants, including plant growth and abiotic stress tolerance. Despite all the knowledge acquired over the years, there is still more to know about how MET and NO act on the tolerance of plants to abiotic stresses. Full article

(This article belongs to the Special Issue Antioxidant Defenses in Plants)

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15 pages, 1454 KiB

Open AccessEditor’s ChoiceReview

Oxidative Stress in Cardiovascular Diseases

by Emilie Dubois-Deruy, Victoriane Peugnet, Annie Turkieh and Florence Pinet

Antioxidants 2020, 9(9), 864; https://doi.org/10.3390/antiox9090864 - 14 Sep 2020

Cited by 233 | Viewed by 15373

Abstract

Reactive oxygen species (ROS) are subcellular messengers in signal transductions pathways with both beneficial and deleterious roles. ROS are generated as a by-product of mitochondrial respiration or metabolism or by specific enzymes such as superoxide dismutases, glutathione peroxidase, catalase, peroxiredoxins, and myeloperoxidases. Under [...] Read more.

Reactive oxygen species (ROS) are subcellular messengers in signal transductions pathways with both beneficial and deleterious roles. ROS are generated as a by-product of mitochondrial respiration or metabolism or by specific enzymes such as superoxide dismutases, glutathione peroxidase, catalase, peroxiredoxins, and myeloperoxidases. Under physiological conditions, the low levels of ROS production are equivalent to their detoxification, playing a major role in cellular signaling and function. In pathological situations, particularly atherosclerosis or hypertension, the release of ROS exceeds endogenous antioxidant capacity, leading to cell death. At cardiovascular levels, oxidative stress is highly implicated in myocardial infarction, ischemia/reperfusion, or heart failure. Here, we will first detail the physiological role of low ROS production in the heart and the vessels. Indeed, ROS are able to regulate multiple cardiovascular functions, such as cell proliferation, migration, and death. Second, we will investigate the implication of oxidative stress in cardiovascular diseases. Then, we will focus on ROS produced by NAPDH oxidase or during endothelial or mitochondrial dysfunction. Given the importance of oxidative stress at the cardiovascular level, antioxidant therapies could be a real benefit. In the last part of this review, we will detail the new therapeutic strategies potentially involved in cardiovascular protection and currently under study. Full article

(This article belongs to the Special Issue Oxidative Stress in Vascular Pathophysiology)

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19 pages, 4744 KiB

Open AccessEditor’s ChoiceArticle

Anti-inflammatory and Anti-oxidant Activity of Hidrox^® in Rotenone-Induced Parkinson’s Disease in Mice

by Rosalba Siracusa, Maria Scuto, Roberta Fusco, Angela Trovato, Maria Laura Ontario, Roberto Crea, Rosanna Di Paola, Salvatore Cuzzocrea and Vittorio Calabrese

Antioxidants 2020, 9(9), 824; https://doi.org/10.3390/antiox9090824 - 03 Sep 2020

Cited by 104 | Viewed by 9002

Abstract

Background: In developed countries, the extension of human life is increasingly accompanied by a progressive increase in neurodegenerative diseases, most of which do not yet have effective therapy but only symptomatic treatments. In recent years, plant polyphenols have aroused considerable interest in the [...] Read more.

Background: In developed countries, the extension of human life is increasingly accompanied by a progressive increase in neurodegenerative diseases, most of which do not yet have effective therapy but only symptomatic treatments. In recent years, plant polyphenols have aroused considerable interest in the scientific community. The mechanisms currently hypothesized for the pathogenesis of Parkinson’s disease (PD) are neuroinflammation, oxidative stress and apoptosis. Hydroxytyrosol (HT), the main component of Hidrox^® (HD), has been shown to have some of the highest free radical evacuation and anti-inflammatory activities. Here we wanted to study the role of HD on the neurobiological and behavioral alterations induced by rotenone. Methods: A study was conducted in which mice received HD (10 mg/kg, i.p.) concomitantly with rotenone (5 mg/kg, o.s.) for 28 days. Results: Locomotor activity, catalepsy, histological damage and several characteristic markers of the PD, such as the dopamine transporter (DAT) content, tyrosine hydroxylase (TH) and accumulation of α-synuclein, have been evaluated. Moreover, we observed the effects of HD on oxidative stress, neuroinflammation, apoptosis and inflammasomes. Taken together, the results obtained highlight HD’s ability to reduce the loss of dopaminergic neurons and the damage associated with it by counteracting the three main mechanisms of PD pathogenesis. Conclusion: HD is subject to fewer regulations than traditional drugs to improve patients’ brain health and could represent a promising nutraceutical choice to prevent PD. Full article

(This article belongs to the Special Issue Dietary Antioxidants for Modulating the Aging Processes)

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23 pages, 1588 KiB

Open AccessEditor’s ChoiceReview

Melatonin-Induced Water Stress Tolerance in Plants: Recent Advances

by Mohamed Moustafa-Farag, Ahmed Mahmoud, Marino B. Arnao, Mohamed S. Sheteiwy, Mohamed Dafea, Mahmoud Soltan, Amr Elkelish, Mirza Hasanuzzaman and Shaoying Ai

Antioxidants 2020, 9(9), 809; https://doi.org/10.3390/antiox9090809 - 01 Sep 2020

Cited by 102 | Viewed by 7252

Abstract

Water stress (drought and waterlogging) is severe abiotic stress to plant growth and development. Melatonin, a bioactive plant hormone, has been widely tested in drought situations in diverse plant species, while few studies on the role of melatonin in waterlogging stress conditions have [...] Read more.

Water stress (drought and waterlogging) is severe abiotic stress to plant growth and development. Melatonin, a bioactive plant hormone, has been widely tested in drought situations in diverse plant species, while few studies on the role of melatonin in waterlogging stress conditions have been published. In the current review, we analyze the biostimulatory functions of melatonin on plants under both drought and waterlogging stresses. Melatonin controls the levels of reactive oxygen and nitrogen species and positively changes the molecular defense to improve plant tolerance against water stress. Moreover, the crosstalk of melatonin and other phytohormones is a key element of plant survival under drought stress, while this relationship needs further investigation under waterlogging stress. In this review, we draw the complete story of water stress on both sides—drought and waterlogging—through discussing the previous critical studies under both conditions. Moreover, we suggest several research directions, especially for waterlogging, which remains a big and vague piece of the melatonin and water stress puzzle. Full article

(This article belongs to the Special Issue Approaches in Enhancing Antioxidant Defense in Plants)

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13 pages, 1704 KiB

Open AccessEditor’s ChoiceArticle

S-Thiolation Targets Albumin in Heart Failure

by Maura Brioschi, Erica Gianazza, Alice Mallia, Beatrice Zoanni, Alessandra Altomare, Alma Martinez Fernandez, Piergiuseppe Agostoni, Giancarlo Aldini and Cristina Banfi

Antioxidants 2020, 9(8), 763; https://doi.org/10.3390/antiox9080763 - 17 Aug 2020

Cited by 18 | Viewed by 3100

Abstract

Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group. In this study, we [...] Read more.

Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group. In this study, we assessed qualitative and quantitative changes in HSA in patients with heart failure (HF) and their relationship with the severity of the disease. We detected by means of mass spectrometry a global decrease of the HSA content in the plasma of HF patients in respect to control subjects, a significant increase of thio-HSA with a concomitant decrease in the reduced form of albumin. Cysteine and, at a lesser extent, homocysteine represent the most abundant thiol bound to HSA. A strong inverse correlation was also observed between cysteine-HSA and peak VO₂/kg, an index of oxygen consumption associated with HF severity. Moreover, in HL-1 cardiomyocytes incubated with H₂O₂, we showed a significant decrease of cell viability in cells treated with thio-HSA in respect to restored native-HSA. In conclusion, we found for the first time that S-thiolation of albumin is increased in the plasma of HF patients and induced changes in the structure and antioxidant function of HSA, likely contributing to HF progression. Full article

(This article belongs to the Section Aberrant Oxidation of Biomolecules)

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14 pages, 643 KiB

Open AccessEditor’s ChoiceReview

Squalene: More than a Step toward Sterols

by Marco Micera, Alfonso Botto, Federica Geddo, Susanna Antoniotti, Cinzia Margherita Bertea, Renzo Levi, Maria Pia Gallo and Giulia Querio

Antioxidants 2020, 9(8), 688; https://doi.org/10.3390/antiox9080688 - 02 Aug 2020

Cited by 57 | Viewed by 8152

Abstract

Squalene (SQ) is a natural triterpene widely distributed in nature. It is a metabolic intermediate of the sterol biosynthetic pathway and represents a possible target in different metabolic and oxidative stress-related disorders. Growing interest has been focused on SQ’s antioxidant properties, derived from [...] Read more.

Squalene (SQ) is a natural triterpene widely distributed in nature. It is a metabolic intermediate of the sterol biosynthetic pathway and represents a possible target in different metabolic and oxidative stress-related disorders. Growing interest has been focused on SQ’s antioxidant properties, derived from its chemical structure. Strong evidence provided by ex vivo models underline its scavenging activity towards free radicals, whereas only a few studies have highlighted its effect in cellular models of oxidative stress. Given the role of unbalanced free radicals in both the onset and progression of several cardiovascular diseases, an in depth evaluation of SQ’s contribution to antioxidant defense mechanisms could represent a strategic approach in dealing with these pathological conditions. At present experimental results overall show a double-edged sword role of squalene in cardiovascular diseases and its function has to be better elucidated in order to establish intervention lines focused on its features. This review aims to summarize current knowledge about endogenous and exogenous sources of SQ and to point out the controversial role of SQ in cardiovascular physiology. Full article

(This article belongs to the Special Issue Redox and Nitrosative Signaling and Stress)

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21 pages, 10352 KiB

Open AccessEditor’s ChoiceArticle

Saponin Formosanin C-Induced Ferritinophagy and Ferroptosis in Human Hepatocellular Carcinoma Cells

by Pin-Lun Lin, Han-Hsuan Tang, Shan-Ying Wu, Ning-Sing Shaw and Chun-Li Su

Antioxidants 2020, 9(8), 682; https://doi.org/10.3390/antiox9080682 - 29 Jul 2020

Cited by 69 | Viewed by 5116

Abstract

Ferroptosis, a recently discovered form of iron-dependent cell death, requires an increased level of lipid-reactive oxygen species (ROS). Ferritinophagy, a ferritin degradation pathway, depends on a selective autophagic cargo receptor (NCOA4). By screening various types of natural compounds, formosanin C (FC) was identified [...] Read more.

Ferroptosis, a recently discovered form of iron-dependent cell death, requires an increased level of lipid-reactive oxygen species (ROS). Ferritinophagy, a ferritin degradation pathway, depends on a selective autophagic cargo receptor (NCOA4). By screening various types of natural compounds, formosanin C (FC) was identified as a novel ferroptosis inducer, characterized by attenuations of FC-induced viability inhibition and lipid ROS formation in the presence of ferroptosis inhibitor. FC also induced autophagic flux, evidenced by preventing autophagic marker LC3-II degradation and increasing yellow LC3 puncta in tandem fluorescent-tagged LC3 (mRFP-GFP) reporter plasmid (ptfLC3) transfected cells when combined with autophagic flux inhibitor. It is noteworthy that FC-induced ferroptosis and autophagic flux were stronger in HepG2 cells expressing higher NCOA4 and lower ferritin heavy chain 1 (FTH1) levels, agreeing with the results of gene expression analysis using CTRP and PRISM, indicating that FTH1 expression level exhibited a significant negative correlation with the sensitivity of the cells to a ferroptosis inducer. Confocal and electron microscopy confirmed the pronounced involvement of ferritinophagy in FC-induced ferroptosis in the cells with elevated NCOA4. Since ferroptosis is a non-apoptotic form of cell death, our data suggest FC has chemotherapeutic potential against apoptosis-resistant HCC with a higher NCOA4 expression via ferritinophagy. Full article

(This article belongs to the Special Issue Oxidative stress and Applied Biology)

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52 pages, 2770 KiB

Open AccessEditor’s ChoiceReview

Reactive Oxygen Species and Antioxidant Defense in Plants under Abiotic Stress: Revisiting the Crucial Role of a Universal Defense Regulator

by Mirza Hasanuzzaman, M.H.M. Borhannuddin Bhuyan, Faisal Zulfiqar, Ali Raza, Sayed Mohammad Mohsin, Jubayer Al Mahmud, Masayuki Fujita and Vasileios Fotopoulos

Antioxidants 2020, 9(8), 681; https://doi.org/10.3390/antiox9080681 - 29 Jul 2020

Cited by 1241 | Viewed by 37580

Abstract

Global climate change and associated adverse abiotic stress conditions, such as drought, salinity, heavy metals, waterlogging, extreme temperatures, oxygen deprivation, etc., greatly influence plant growth and development, ultimately affecting crop yield and quality, as well as agricultural sustainability in general. Plant cells produce [...] Read more.

Global climate change and associated adverse abiotic stress conditions, such as drought, salinity, heavy metals, waterlogging, extreme temperatures, oxygen deprivation, etc., greatly influence plant growth and development, ultimately affecting crop yield and quality, as well as agricultural sustainability in general. Plant cells produce oxygen radicals and their derivatives, so-called reactive oxygen species (ROS), during various processes associated with abiotic stress. Moreover, the generation of ROS is a fundamental process in higher plants and employs to transmit cellular signaling information in response to the changing environmental conditions. One of the most crucial consequences of abiotic stress is the disturbance of the equilibrium between the generation of ROS and antioxidant defense systems triggering the excessive accumulation of ROS and inducing oxidative stress in plants. Notably, the equilibrium between the detoxification and generation of ROS is maintained by both enzymatic and nonenzymatic antioxidant defense systems under harsh environmental stresses. Although this field of research has attracted massive interest, it largely remains unexplored, and our understanding of ROS signaling remains poorly understood. In this review, we have documented the recent advancement illustrating the harmful effects of ROS, antioxidant defense system involved in ROS detoxification under different abiotic stresses, and molecular cross-talk with other important signal molecules such as reactive nitrogen, sulfur, and carbonyl species. In addition, state-of-the-art molecular approaches of ROS-mediated improvement in plant antioxidant defense during the acclimation process against abiotic stresses have also been discussed. Full article

(This article belongs to the Special Issue Antioxidant Defenses in Plants)

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20 pages, 1038 KiB

Open AccessEditor’s ChoiceReview

Redox Imbalances in Ageing and Metabolic Alterations: Implications in Cancer and Cardiac Diseases. An Overview from the Working Group of Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology (SIC)

by Valentina Mercurio, Alessandra Cuomo, Christian Cadeddu Dessalvi, Martino Deidda, Daniela Di Lisi, Giuseppina Novo, Roberta Manganaro, Concetta Zito, Ciro Santoro, Pietro Ameri, Paolo Spallarossa, Eleonora Arboscello, Carlo Gabriele Tocchetti and Claudia Penna

Antioxidants 2020, 9(7), 641; https://doi.org/10.3390/antiox9070641 - 21 Jul 2020

Cited by 24 | Viewed by 3618

Abstract

Metabolic syndrome (MetS) is a well established risk factor for cardiovascular (CV) diseases. In addition, several studies indicate that MetS correlates with the increased risk of cancer in adults. The mechanisms linking MetS and cancer are not fully understood. Several risk factors involved [...] Read more.

Metabolic syndrome (MetS) is a well established risk factor for cardiovascular (CV) diseases. In addition, several studies indicate that MetS correlates with the increased risk of cancer in adults. The mechanisms linking MetS and cancer are not fully understood. Several risk factors involved in MetS are also cancer risk factors, such as the consumption of high calorie-food or high fat intake, low fibre intake, and sedentary lifestyle. Other common aspects of both cancer and MetS are oxidative stress and inflammation. In addition, some anticancer treatments can induce cardiotoxicity, including, for instance, left ventricular (LV) dysfunction and heart failure (HF), endothelial dysfunction and hypertension. In this review, we analyse several aspects of MetS, cancer and cardiotoxicity from anticancer drugs. In particular, we focus on oxidative stress in ageing, cancer and CV diseases, and we analyse the connections among CV risk factors, cancer and cardiotoxicity from anticancer drugs. Full article

(This article belongs to the Special Issue Redox and Nitrosative Signaling and Stress)

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16 pages, 986 KiB

Open AccessEditor’s ChoiceReview

The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19

by Francesca Silvagno, Annamaria Vernone and Gian Piero Pescarmona

Antioxidants 2020, 9(7), 624; https://doi.org/10.3390/antiox9070624 - 16 Jul 2020

Cited by 141 | Viewed by 31423

Abstract

The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease [...] Read more.

The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokine storm and patients die from acute respiratory distress syndrome, whereas in many cases the disease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key anti-oxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease. Full article

(This article belongs to the Special Issue ROS and COVID)

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24 pages, 1612 KiB

Open AccessEditor’s ChoiceReview

Hydrogen Sulfide: From a Toxic Molecule to a Key Molecule of Cell Life

by Angeles Aroca, Cecilia Gotor, Diane C. Bassham and Luis C. Romero

Antioxidants 2020, 9(7), 621; https://doi.org/10.3390/antiox9070621 - 15 Jul 2020

Cited by 88 | Viewed by 9708

Abstract

Hydrogen sulfide (H₂S) has always been considered toxic, but a huge number of articles published more recently showed the beneficial biochemical properties of its endogenous production throughout all regna. In this review, the participation of H₂S in many [...] Read more.

Hydrogen sulfide (H₂S) has always been considered toxic, but a huge number of articles published more recently showed the beneficial biochemical properties of its endogenous production throughout all regna. In this review, the participation of H₂S in many physiological and pathological processes in animals is described, and its importance as a signaling molecule in plant systems is underlined from an evolutionary point of view. H₂S quantification methods are summarized and persulfidation is described as the underlying mechanism of action in plants, animals and bacteria. This review aims to highlight the importance of its crosstalk with other signaling molecules and its fine regulation for the proper function of the cell and its survival. Full article

(This article belongs to the Special Issue Hydrogen Sulfide in Biology)

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