Antioxidants

15 pages, 2100 KiB

Open AccessEditor’s ChoiceArticle

Polyphenols Attenuate Highly-Glycosylated Haemoglobin-Induced Damage in Human Peritoneal Mesothelial Cells

by Carolina Sánchez-Rodríguez, Concepción Peiró, Leocadio Rodríguez-Mañas and Julián Nevado

Antioxidants 2020, 9(7), 572; https://doi.org/10.3390/antiox9070572 - 01 Jul 2020

Cited by 3 | Viewed by 3576

We investigated the cytoprotective role of the dietary polyphenols on putative damage induced by Amadori adducts in Human Peritoneal Mesothelial Cells (HPMCs). Increased accumulation of early products of non-enzymatic protein glycation—Amadori adducts—in the peritoneal dialysis fluid due to their high glucose, induces severe [...] Read more.

We investigated the cytoprotective role of the dietary polyphenols on putative damage induced by Amadori adducts in Human Peritoneal Mesothelial Cells (HPMCs). Increased accumulation of early products of non-enzymatic protein glycation—Amadori adducts—in the peritoneal dialysis fluid due to their high glucose, induces severe damage in mesothelial cells during peritoneal dialysis. Dietary polyphenols reportedly have numerous health benefits in various diseases and have been used as an efficient antioxidant in the context of several oxidative stress-related pathologies. HPMCs isolated from different patients were exposed to Amadori adducts (highly glycated haemoglobin, at physiological concentrations), and subsequently treated with several polyphenols, mostly presented in our Mediterranean diet. We studied several Amadori-induced effects in pro-apoptotic and oxidative stress markers, as well as the expression of several pro-inflammatory genes (nuclear factor-kappaB, NF-kB; inducible Nitric Oxide synthetase, iNOS), different caspase-activities, level of P53 protein or production of different reactive oxygen species in the presence of different polyphenols. In fact, cytoprotective agents such as dietary polyphenols may represent an alternate approach to protect mesothelial cells from the cytotoxicity of Amadori adducts. The interference with the Amadori adducts-triggered mechanisms could represent a therapeutic tool to reduce complications associated with peritoneal dialysis in the peritoneum, helping to maintain peritoneal membrane function longer in patients undergoing peritoneal dialysis. Full article

(This article belongs to the Special Issue Effect of Antioxidant Therapy on Oxidative Stress In Vivo)

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14 pages, 1062 KiB

Open AccessEditor’s ChoiceReview

An Update on Mitochondrial Reactive Oxygen Species Production

by Ryan J. Mailloux

Antioxidants 2020, 9(6), 472; https://doi.org/10.3390/antiox9060472 - 02 Jun 2020

Cited by 129 | Viewed by 8258

Abstract

Mitochondria are quantifiably the most important sources of superoxide (O₂^●−) and hydrogen peroxide (H₂O₂) in mammalian cells. The overproduction of these molecules has been studied mostly in the contexts of the pathogenesis of human diseases and [...] Read more.

Mitochondria are quantifiably the most important sources of superoxide (O₂^●−) and hydrogen peroxide (H₂O₂) in mammalian cells. The overproduction of these molecules has been studied mostly in the contexts of the pathogenesis of human diseases and aging. However, controlled bursts in mitochondrial ROS production, most notably H₂O₂, also plays a vital role in the transmission of cellular information. Striking a balance between utilizing H₂O₂ in second messaging whilst avoiding its deleterious effects requires the use of sophisticated feedback control and H₂O₂ degrading mechanisms. Mitochondria are enriched with H₂O₂ degrading enzymes to desensitize redox signals. These organelles also use a series of negative feedback loops, such as proton leaks or protein S-glutathionylation, to inhibit H₂O₂ production. Understanding how mitochondria produce ROS is also important for comprehending how these organelles use H₂O₂ in eustress signaling. Indeed, twelve different enzymes associated with nutrient metabolism and oxidative phosphorylation (OXPHOS) can serve as important ROS sources. This includes several flavoproteins and respiratory complexes I-III. Progress in understanding how mitochondria generate H₂O₂ for signaling must also account for critical physiological factors that strongly influence ROS production, such as sex differences and genetic variances in genes encoding antioxidants and proteins involved in mitochondrial bioenergetics. In the present review, I provide an updated view on how mitochondria budget cellular H₂O₂ production. These discussions will focus on the potential addition of two acyl-CoA dehydrogenases to the list of ROS generators and the impact of important phenotypic and physiological factors such as tissue type, mouse strain, and sex on production by these individual sites. Full article

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

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13 pages, 1902 KiB

Open AccessEditor’s ChoiceArticle

Protective Effects of Myricetin on Benzo[a]pyrene-Induced 8-Hydroxy-2′-Deoxyguanosine and BPDE-DNA Adduct

by Seung-Cheol Jee, Min Kim, Kyeong Seok Kim, Hyung-Sik Kim and Jung-Suk Sung

Antioxidants 2020, 9(5), 446; https://doi.org/10.3390/antiox9050446 - 21 May 2020

Cited by 24 | Viewed by 3919

Abstract

Benzo[a]pyrene (B[a]P), a group 1 carcinogen, induces mutagenic DNA adducts. Myricetin is present in many natural foods with diverse biological activities, such as anti-oxidative and anti-cancer activities. The aim of this study was to investigate the protective effects of myricetin against B[a]P-induced toxicity. [...] Read more.

Benzo[a]pyrene (B[a]P), a group 1 carcinogen, induces mutagenic DNA adducts. Myricetin is present in many natural foods with diverse biological activities, such as anti-oxidative and anti-cancer activities. The aim of this study was to investigate the protective effects of myricetin against B[a]P-induced toxicity. Treatment of B[a]P induced cytotoxicity on HepG2 cells, whereas co-treatment of myricetin with B[a]P reduced the formation of the B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adduct, which recovered cell viability. Furthermore, we found a protective effect of myricetin against B[a]P-induced genotoxicity in rats, via myricetin-induced inhibition of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and BPDE-DNA adduct formation in the liver, kidney, colon, and stomach tissue. This inhibition was more prominent in the liver than in other tissues. Correspondingly, myricetin regulated the phase I and II enzymes that inhibit B[a]P metabolism and B[a]P metabolites conjugated with DNA by reducing and inducing CYP1A1 and glutathione S-transferase (GST) expression, respectively. Taken together, this showed that myricetin attenuated B[a]P-induced genotoxicity via regulation of phase I and II enzymes. Our results suggest that myricetin is anti-genotoxic, and prevents oxidative DNA damage and BPDE-DNA adduct formation via regulation of phase I and II enzymes. Full article

(This article belongs to the Special Issue Oxidative Stress Modulators and Functional Foods)

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28 pages, 5333 KiB

Open AccessEditor’s ChoiceArticle

Melatonin Enhances Palladium-Nanoparticle-Induced Cytotoxicity and Apoptosis in Human Lung Epithelial Adenocarcinoma Cells A549 and H1229

by Sangiliyandi Gurunathan, Muniyandi Jeyaraj, Min-Hee Kang and Jin-Hoi Kim

Antioxidants 2020, 9(4), 357; https://doi.org/10.3390/antiox9040357 - 24 Apr 2020

Cited by 34 | Viewed by 4082

Abstract

Palladium nanoparticles (PdNPs) are increasingly being used in medical and biological applications due to their unique physical and chemical properties. Recent evidence suggests that these nanoparticles can act as both a pro-oxidant and as an antioxidant. Melatonin (MLT), which also shows pro- and [...] Read more.

Palladium nanoparticles (PdNPs) are increasingly being used in medical and biological applications due to their unique physical and chemical properties. Recent evidence suggests that these nanoparticles can act as both a pro-oxidant and as an antioxidant. Melatonin (MLT), which also shows pro- and antioxidant properties, can enhance the efficacy of chemotherapeutic agents when combined with anticancer drugs. Nevertheless, studies regarding the molecular mechanisms underlying the anticancer effects of PdNPs and MLT in cancer cells are still lacking. Therefore, we aimed to investigate the potential toxicological and molecular mechanisms of PdNPs, MLT, and the combination of PdNPs with MLT in A549 lung epithelial adenocarcinoma cells. We evaluated cell viability, cell proliferation, cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis in cells treated with different concentrations of PdNPs and MLT. PdNPs and MLT induced cytotoxicity, which was confirmed by leakage of lactate dehydrogenase, increased intracellular protease, and reduced membrane integrity. Oxidative stress increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO), protein carbonyl content (PCC), lipid hydroperoxide (LHP), and 8-isoprostane. Combining PdNPs with MLT elevated the levels of mitochondrial dysfunction by decreasing mitochondrial membrane potential (MMP), ATP content, mitochondrial number, and expression levels of the main regulators of mitochondrial biogenesis. Additionally, PdNPs and MLT induced apoptosis and oxidative DNA damage due to accumulation of 4-hydroxynonenal (HNE), 8-oxo-2′-deoxyguanosine (8-OhdG), and 8-hydroxyguanosine (8-OHG). Finally, PdNPs and MLT increased mitochondrially mediated stress and apoptosis, which was confirmed by the increased expression levels of apoptotic genes. To our knowledge, this is the first study demonstrating the effects of combining PdNPs and MLT in human lung cancer cells. These findings provide valuable insights into the molecular mechanisms involved in PdNP- and MLT-induced toxicity, and it may be that this combination therapy could be a potential effective therapeutic approach. This combination effect provides information to support the clinical evaluation of PdNPs and MLT as a suitable agents for lung cancer treatment, and the combined effect provides therapeutic value, as non-toxic concentrations of PdNPs and MLT are more effective, better tolerated, and show less adverse effects. Finally, this study suggests that MLT could be used as a supplement in nano-mediated combination therapies used to treat lung cancer. Full article

(This article belongs to the Section ROS, RNS and RSS)

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13 pages, 910 KiB

Open AccessEditor’s ChoiceReview

Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms

by Justyna Godos, Walter Currenti, Donato Angelino, Pedro Mena, Sabrina Castellano, Filippo Caraci, Fabio Galvano, Daniele Del Rio, Raffaele Ferri and Giuseppe Grosso

Antioxidants 2020, 9(4), 346; https://doi.org/10.3390/antiox9040346 - 23 Apr 2020

Cited by 152 | Viewed by 23787

Abstract

Over the last decades, there has been a substantial increase in the prevalence of mental health disorders, including an increased prevalence of depression, anxiety, cognitive, and sleep disorders. Diet and its bioactive components have been recognized among the modifiable risk factors, possibly influencing [...] Read more.

Over the last decades, there has been a substantial increase in the prevalence of mental health disorders, including an increased prevalence of depression, anxiety, cognitive, and sleep disorders. Diet and its bioactive components have been recognized among the modifiable risk factors, possibly influencing their pathogenesis. This review aimed to summarize molecular mechanisms underlying the putative beneficial effects toward brain health of different dietary factors, such as micro- and macronutrient intake and habits, such as feeding time and circadian rhythm. The role of hormonal homeostasis in the context of glucose metabolism and adiponectin regulation and its impact on systemic and neuro-inflammation has also been considered and deepened. In addition, the effect of individual bioactive molecules exerting antioxidant activities and acting as anti-inflammatory agents, such as omega-3 fatty acids and polyphenols, considered beneficial for the central nervous system via modulation of adult neurogenesis, synaptic and neuronal plasticity, and microglia activation has been summarized. An overview of the regulation of the gut–brain axis and its effect on the modulation of systemic inflammation and oxidative stress has been provided. Finally, the impact of bioactive molecules on inflammation and oxidative stress and its association with brain health has been summarized. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Brain Health: Focus on Cognitive and Affective Disorders)

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19 pages, 3047 KiB

Open AccessEditor’s ChoiceReview

Molecular Mechanism of Oxidation of P700 and Suppression of ROS Production in Photosystem I in Response to Electron-Sink Limitations in C3 Plants

by Chikahiro Miyake

Antioxidants 2020, 9(3), 230; https://doi.org/10.3390/antiox9030230 - 11 Mar 2020

Cited by 52 | Viewed by 7036

Abstract

Photosynthesis fixes CO₂ and converts it to sugar, using chemical-energy compounds of both NADPH and ATP, which are produced in the photosynthetic electron transport system. The photosynthetic electron transport system absorbs photon energy to drive electron flow from Photosystem II (PSII) to [...] Read more.

Photosynthesis fixes CO₂ and converts it to sugar, using chemical-energy compounds of both NADPH and ATP, which are produced in the photosynthetic electron transport system. The photosynthetic electron transport system absorbs photon energy to drive electron flow from Photosystem II (PSII) to Photosystem I (PSI). That is, both PSII and PSI are full of electrons. O₂ is easily reduced to a superoxide radical (O₂⁻) at the reducing side, i.e., the acceptor side, of PSI, which is the main production site of reactive oxygen species (ROS) in photosynthetic organisms. ROS-dependent inactivation of PSI in vivo has been reported, where the electrons are accumulated at the acceptor side of PSI by artificial treatments: exposure to low temperature and repetitive short-pulse (rSP) illumination treatment, and the accumulated electrons flow to O₂, producing ROS. Recently, my group found that the redox state of the reaction center of chlorophyll P700 in PSI regulates the production of ROS: P700 oxidation suppresses the production of O₂⁻ and prevents PSI inactivation. This is why P700 in PSI is oxidized upon the exposure of photosynthesis organisms to higher light intensity and/or low CO₂ conditions, where photosynthesis efficiency decreases. In this study, I introduce a new molecular mechanism for the oxidation of P700 in PSI and suppression of ROS production from the robust relationship between the light and dark reactions of photosynthesis. The accumulated protons in the lumenal space of the thylakoid membrane and the accumulated electrons in the plastoquinone (PQ) pool drive the rate-determining step of the P700 photo-oxidation reduction cycle in PSI from the photo-excited P700 oxidation to the reduction of the oxidized P700, thereby enhancing P700 oxidation. Full article

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

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48 pages, 1944 KiB

Open AccessEditor’s ChoiceReview

Potential Applications of NRF2 Modulators in Cancer Therapy

by Emiliano Panieri, Aleksandra Buha, Pelin Telkoparan-Akillilar, Dilek Cevik, Demetrios Kouretas, Aristidis Veskoukis, Zoi Skaperda, Aristidis Tsatsakis, David Wallace, Sibel Suzen and Luciano Saso

Antioxidants 2020, 9(3), 193; https://doi.org/10.3390/antiox9030193 - 25 Feb 2020

Cited by 99 | Viewed by 11668

Abstract

The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has [...] Read more.

The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2. Full article

(This article belongs to the Special Issue Modulators of Oxidative Stress: Chemical and Pharmacological Aspects)

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16 pages, 2680 KiB

Open AccessEditor’s ChoiceArticle

Inactivation of Carbonyl-Detoxifying Enzymes by H₂O₂ Is a Trigger to Increase Carbonyl Load for Initiating Programmed Cell Death in Plants

by Md. Sanaullah Biswas, Ryota Terada and Jun’ichi Mano

Antioxidants 2020, 9(2), 141; https://doi.org/10.3390/antiox9020141 - 06 Feb 2020

Cited by 15 | Viewed by 3318

Abstract

H₂O₂-induced programmed cell death (PCD) of tobacco Bright Yellow-2 (BY-2) cells is mediated by reactive carbonyl species (RCS), degradation products of lipid peroxides, which activate caspase-3-like protease (C3LP). Here, we investigated the mechanism of RCS accumulation in the H [...] Read more.

H₂O₂-induced programmed cell death (PCD) of tobacco Bright Yellow-2 (BY-2) cells is mediated by reactive carbonyl species (RCS), degradation products of lipid peroxides, which activate caspase-3-like protease (C3LP). Here, we investigated the mechanism of RCS accumulation in the H₂O₂-induced PCD of BY-2 cells. The following biochemical changes were observed in 10-min response to a lethal dose (1.0 mM) of H₂O₂, but they did not occur in a sublethal dose (0.5 mM) of H₂O₂. (1) The C3LP activity was increased twofold. (2) The intracellular levels of RCS, i.e., 4-hydroxy-(E)-hexenal and 4-hydroxy-(E)-nonenal (HNE), were increased 1.2–1.5-fold. (3) The activity of a reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent carbonyl reductase, scavenging HNE, and n-hexanal was decreased. Specifically, these are the earliest events leading to PCD. The proteasome inhibitor MG132 suppressed the H₂O₂-induced PCD, indicating that the C3LP activity of the β1 subunit of the 20S proteasome was responsible for PCD. The addition of H₂O₂ to cell-free protein extract inactivated the carbonyl reductase. Taken together, these results suggest a PCD-triggering mechanism in which H₂O₂ first inactivates a carbonyl reductase(s), allowing RCS levels to rise, and eventually leads to the activation of the C3LP activity of 20S proteasome. The carbonyl reductase thus acts as an ROS sensor for triggering PCD. Full article

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

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13 pages, 992 KiB

Open AccessEditor’s ChoiceReview

Polyphenols from Food and Natural Products: Neuroprotection and Safety

by Rui F. M. Silva and Lea Pogačnik

Antioxidants 2020, 9(1), 61; https://doi.org/10.3390/antiox9010061 - 10 Jan 2020

Cited by 177 | Viewed by 11147

Abstract

Polyphenols are naturally occurring micronutrients that are present in many food sources. Besides being potent antioxidants, these molecules may also possess anti-inflammatory properties. Many studies have highlighted their potential role in the prevention and treatment of various pathological conditions connected to oxidative stress [...] Read more.

Polyphenols are naturally occurring micronutrients that are present in many food sources. Besides being potent antioxidants, these molecules may also possess anti-inflammatory properties. Many studies have highlighted their potential role in the prevention and treatment of various pathological conditions connected to oxidative stress and inflammation (e.g., cancer, and cardiovascular and neurodegenerative disorders). Neurodegenerative diseases are globally one of the main causes of death and represent an enormous burden in terms of human suffering, social distress, and economic costs. Recent data expanded on the initial antioxidant-based mechanism of polyphenols’ action by showing that they are also able to modulate several cell-signaling pathways and mediators. The proposed benefits of polyphenols, either as protective/prophylactic substances or as therapeutic molecules, may be achieved by the consumption of a natural polyphenol-enriched diet, by their use as food supplements, or with formulations as pharmaceutical drugs/nutraceuticals. It has also been proved that the health effects of polyphenols depend on the consumed amount and their bioavailability. However, their overconsumption may raise safety concerns due to the accumulation of high levels of these molecules in the organism, particularly if we consider the loose regulatory legislation regarding the commercialization and use of food supplements. This review addresses the main beneficial effects of food polyphenols, and focuses on neuroprotection and the safety issues related to overconsumption. Full article

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

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17 pages, 1083 KiB

Open AccessEditor’s ChoiceArticle

Serratia marcescens BM1 Enhances Cadmium Stress Tolerance and Phytoremediation Potential of Soybean Through Modulation of Osmolytes, Leaf Gas Exchange, Antioxidant Machinery, and Stress-Responsive Genes Expression

by Mohamed A. El-Esawi, Amr Elkelish, Mona Soliman, Hosam O. Elansary, Abbu Zaid and Shabir H. Wani

Antioxidants 2020, 9(1), 43; https://doi.org/10.3390/antiox9010043 - 04 Jan 2020

Cited by 96 | Viewed by 6050

Abstract

The heavy metal contamination in plant-soil environment has increased manifold recently. In order to reduce the harmful effects of metal stress in plants, the application of beneficial soil microbes is gaining much attention. In the present research, the role of Serratia marcescens BM1 [...] Read more.

The heavy metal contamination in plant-soil environment has increased manifold recently. In order to reduce the harmful effects of metal stress in plants, the application of beneficial soil microbes is gaining much attention. In the present research, the role of Serratia marcescens BM1 in enhancing cadmium (Cd) stress tolerance and phytoremediation potential of soybean plants, was investigated. Exposure of soybean plants to two Cd doses (150 and 300 µM) significantly reduced plant growth, biomass, gas exchange attributes, nutrients uptake, antioxidant capacity, and the contents of chlorophyll, total phenolics, flavonoids, soluble sugars, and proteins. Additionally, Cd induced the stress levels of Cd, proline, glycine betaine, hydrogen peroxide, malondialdehyde, antioxidant enzymes (i.e., catalase, CAT; ascorbate peroxidase, APX; superoxide dismutase, SOD; peroxidise, POD), and the expression of stress-related genes (i.e., APX, CAT, Fe-SOD, POD, CHI, CHS, PHD2, VSO, NR, and P5CS) in soybean leaves. On the other hand, inoculation of Cd-stressed soybean plants with Serratia marcescens BM1 significantly enhanced the plant growth, biomass, gas exchange attributes, nutrients uptake, antioxidant capacity, and the contents of chlorophyll, total phenolics, flavonoids, soluble sugars, and proteins. Moreover, Serratia marcescens BM1 inoculation reduced the levels of cadmium and oxidative stress markers, but significantly induced the activities of antioxidant enzymes and the levels of osmolytes and stress-related genes expression in Cd-stressed plants. The application of 300 µM CdCl₂ and Serratia marcescens triggered the highest expression levels of stress-related genes. Overall, this study suggests that inoculation of soybean plants with Serratia marcescens BM1 promotes phytoremediation potential and Cd stress tolerance by modulating the photosynthetic attributes, osmolytes biosynthesis, antioxidants machinery, and the expression of stress-related genes. Full article

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

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