Editorial

6 pages, 204 KiB

Open AccessEditorial

Modulators of Oxidative Stress: Chemical and Pharmacological Aspects

by Luciano Saso, Hande Gürer-Orhan and Višnja Stepanić

Antioxidants 2020, 9(8), 657; https://doi.org/10.3390/antiox9080657 - 24 Jul 2020

Cited by 10 | Viewed by 3222

Oxidative stress is represented as an imbalance between reactive oxygen species (ROS) production and the response of antioxidant proteins [...] Full article

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

Research

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15 pages, 6091 KiB

Open AccessArticle

The Role of Sirtuin 3 in Radiation-Induced Long-Term Persistent Liver Injury

by Francesca V. LoBianco, Kimberly J. Krager, Gwendolyn S. Carter, Sinthia Alam, Youzhong Yuan, Elise G. Lavoie, Jonathan A. Dranoff and Nukhet Aykin-Burns

Antioxidants 2020, 9(5), 409; https://doi.org/10.3390/antiox9050409 - 11 May 2020

Cited by 11 | Viewed by 2738

Abstract

In patients with abdominal region cancers, ionizing radiation (IR)-induced long-term liver injury is a major limiting factor in the use of radiotherapy. Previously, the major mitochondrial deacetylase, sirtuin 3 (SIRT3), has been implicated to play an important role in the development of acute [...] Read more.

In patients with abdominal region cancers, ionizing radiation (IR)-induced long-term liver injury is a major limiting factor in the use of radiotherapy. Previously, the major mitochondrial deacetylase, sirtuin 3 (SIRT3), has been implicated to play an important role in the development of acute liver injury after total body irradiation but no studies to date have examined the role of SIRT3 in liver’s chronic response to radiation. In the current study, ten-month-old Sirt3^−/− and Sirt3^+/+ male mice received 24 Gy radiation targeted to liver. Six months after exposure, irradiated Sirt3^−/− mice livers demonstrated histopathological elevations in inflammatory infiltration, the loss of mature bile ducts and higher DNA damage (TUNEL) as well as protein oxidation (3-nitrotyrosine). In addition, increased expression of inflammatory chemokines (IL-6, IL-1β, TGF-β) and fibrotic factors (Procollagen 1, α-SMA) were also measured in Sirt3^−/− mice following 24 Gy IR. The alterations measured in enzymatic activities of catalase, glutathione peroxidase, and glutathione reductase in the livers of irradiated Sirt3^−/− mice also implied that hydrogen peroxide and hydroperoxide sensitive signaling cascades in the absence of SIRT3 might contribute to the IR-induced long-term liver injury. Full article

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

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17 pages, 3807 KiB

Open AccessArticle

Ezetimibe Prevents Ischemia/Reperfusion-Induced Oxidative Stress and Up-Regulates Nrf2/ARE and UPR Signaling Pathways

by Denise Peserico, Chiara Stranieri, Ulisse Garbin, Chiara Mozzini C, Elisa Danese, Luciano Cominacini and Anna M. Fratta Pasini

Antioxidants 2020, 9(4), 349; https://doi.org/10.3390/antiox9040349 - 23 Apr 2020

Cited by 10 | Viewed by 3527

Abstract

Background: While reperfusion is crucial for survival after an episode of ischemia, it also causes oxidative stress. Nuclear factor-E2-related factor 2 (Nrf2) and unfolded protein response (UPR) are protective against oxidative stress and endoplasmic reticulum (ER) stress. Ezetimibe, a cholesterol absorption inhibitor, has [...] Read more.

Background: While reperfusion is crucial for survival after an episode of ischemia, it also causes oxidative stress. Nuclear factor-E2-related factor 2 (Nrf2) and unfolded protein response (UPR) are protective against oxidative stress and endoplasmic reticulum (ER) stress. Ezetimibe, a cholesterol absorption inhibitor, has been shown to activate the AMP-activated protein kinase (AMPK)/Nrf2 pathway. In this study we evaluated whether Ezetimibe affects oxidative stress and Nrf2 and UPR gene expression in cellular models of ischemia-reperfusion (IR). Methods: Cultured cells were subjected to simulated IR with or without Ezetimibe. Results: IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Ezetimibe significantly decreased the cellular ROS formation and apoptosis induced by IR. These effects were paralleled by the up-regulation of Nrf2/ARE and ATF6 gene expression and by a down-regulation of CHOP. We also found that Nrf2 activation was dependent on AMPK, since Compound C, a pan inhibitor of p-AMPK, blunted the activation of Nrf2. Conclusions: Ezetimibe counteracts IR-induced oxidative stress and induces Nrf2 and UPR pathway activation. Full article

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

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11 pages, 651 KiB

Open AccessArticle

Effect of Dipeptidyl-Peptidase 4 Inhibitors on Circulating Oxidative Stress Biomarkers in Patients with Type 2 Diabetes Mellitus

by Elisabetta Bigagli, Cristina Luceri, Ilaria Dicembrini, Lorenzo Tatti, Francesca Scavone, Lisa Giovannelli, Edoardo Mannucci and Maura Lodovici

Antioxidants 2020, 9(3), 233; https://doi.org/10.3390/antiox9030233 - 11 Mar 2020

Cited by 7 | Viewed by 2463

Abstract

Pre-clinical studies suggested potential cardiovascular benefits of dipeptidyl peptidase-4 inhibitors (DPP4i), however, clinical trials showed neither beneficial nor detrimental effects in patients with type 2 diabetes mellitus (T2DM). We examined the effects of DPP4i on several circulating oxidative stress markers in a cohort [...] Read more.

Pre-clinical studies suggested potential cardiovascular benefits of dipeptidyl peptidase-4 inhibitors (DPP4i), however, clinical trials showed neither beneficial nor detrimental effects in patients with type 2 diabetes mellitus (T2DM). We examined the effects of DPP4i on several circulating oxidative stress markers in a cohort of 32 T2DM patients (21 males and 11 post-menopausal females), who were already on routine antidiabetic treatment. Propensity score matching was used to adjust demographic and clinical characteristics between patients who received and who did not receive DPP4i. Whole-blood reactive oxygen species (ROS), plasma advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), carbonyl residues, as well as ferric reducing ability of plasma (FRAP) and leukocyte DNA oxidative damage (Fpg sites), were evaluated. With the exception of Fpg sites, that showed a borderline increase in DPP4i users compared to non-users (p = 0.0507), none of the biomarkers measured was affected by DPP4i treatment. An inverse correlation between estimated glomerular filtration rate and AGEs (p < 0.0001) and Fpg sites (p < 0.05) was also observed. This study does not show any major effect of DPP4i on oxidative stress, assessed by several circulating biomarkers of oxidative damage, in propensity score-matched cohorts of T2DM patients. Full article

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

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13 pages, 1476 KiB

Open AccessArticle

Vitamin C Activates the Folate-Mediated One-Carbon Cycle in C2C12 Myoblasts

by Armando Alcazar Magana, Ralph L. Reed, Rony Koluda, Cristobal L. Miranda, Claudia S. Maier and Jan F. Stevens

Antioxidants 2020, 9(3), 217; https://doi.org/10.3390/antiox9030217 - 05 Mar 2020

Cited by 19 | Viewed by 8777

Abstract

Vitamin C (L-ascorbic acid, AA) is an essential cellular antioxidant and cofactor for several α-ketoglutarate-dependent dioxygenases. As an antioxidant, AA interacts with vitamin E to control oxidative stress. While several reports suggest an interaction of AA with folate (vitamin B9) in animals and [...] Read more.

Vitamin C (L-ascorbic acid, AA) is an essential cellular antioxidant and cofactor for several α-ketoglutarate-dependent dioxygenases. As an antioxidant, AA interacts with vitamin E to control oxidative stress. While several reports suggest an interaction of AA with folate (vitamin B9) in animals and humans, little is known about the nature of the interaction and the underlying molecular mechanisms at the cellular level. We used an untargeted metabolomics approach to study the impact of AA on the metabolome of C2C12 myoblast cells. Compared to untreated cells, treatment of C2C12 cells with AA at 100 µM resulted in enhanced concentrations of folic acid (2.5-fold) and 5-methyl-tetrahydrofolate (5-methyl-THF, 10-fold increase) whereas the relative concentrations of 10-formyl-tetrahydrofolate decreased by >90% upon AA pretreatment, indicative of increased utilization for the biosynthesis of active THF metabolites. The impact of AA on the folate-mediated one-carbon cycle further manifested itself as an increase in the levels of methionine, whose formation from homocysteine is 5-methyl-THF dependent, and an increase in thymidine, whose formation from deoxyuridine monophosphate (dUMP) is dependent on 5,10-methylene-THF. These findings shed new light on the interaction of AA with the folate-mediated one-carbon cycle and partially explain clinical findings that AA supplementation enhances erythrocyte folate status and that it may decrease serum levels of homocysteine, which is considered as a biomarker of cardiovascular disease risk. Full article

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

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14 pages, 1925 KiB

Open AccessArticle

Differential Effects of MitoVitE, α-Tocopherol and Trolox on Oxidative Stress, Mitochondrial Function and Inflammatory Signalling Pathways in Endothelial Cells Cultured under Conditions Mimicking Sepsis

by Beverley E. Minter, Damon A. Lowes, Nigel R. Webster and Helen F. Galley

Antioxidants 2020, 9(3), 195; https://doi.org/10.3390/antiox9030195 - 26 Feb 2020

Cited by 21 | Viewed by 3911

Abstract

Sepsis is a life-threatening response to infection associated with inflammation, oxidative stress and mitochondrial dysfunction. We investigated differential effects of three forms of vitamin E, which accumulate in different cellular compartments, on oxidative stress, mitochondrial function, mRNA and protein expression profiles associated with [...] Read more.

Sepsis is a life-threatening response to infection associated with inflammation, oxidative stress and mitochondrial dysfunction. We investigated differential effects of three forms of vitamin E, which accumulate in different cellular compartments, on oxidative stress, mitochondrial function, mRNA and protein expression profiles associated with the human Toll-like receptor (TLR) -2 and -4 pathways. Human endothelial cells were exposed to lipopolysaccharide (LPS)/peptidoglycan G (PepG) to mimic sepsis, MitoVitE, α-tocopherol, or Trolox. Oxidative stress, mitochondrial function, mitochondrial membrane potential and metabolic activity were measured. NFκB-P65, total and phosphorylated inhibitor of NFκB alpha (NFκBIA), and STAT-3 in nuclear extracts, interleukin (IL)-6 and IL-8 production in culture supernatants and cellular mRNA expression of 32 genes involved in Toll-like receptor-2 and -4 pathways were measured. Exposure to LPS/PepG caused increased total radical production (p = 0.022), decreased glutathione ratio (p = 0.016), reduced membrane potential and metabolic activity (both p < 0.0001), increased nuclear NFκB-P65 expression (p = 0.016) and increased IL-6/8 secretion (both p < 0.0001). MitoVitE, α- tocopherol and Trolox were similar in reducing oxidative stress, NFκB activation and interleukin secretion. MitoVitE had widespread downregulatory effects on gene expression. Despite differences in site of actions, all forms of vitamin E were protective under conditions mimicking sepsis. These results challenge the concept that protection inside mitochondria provides better protection. Full article

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

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19 pages, 17006 KiB

Open AccessArticle

Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice

by Marija Pinterić, Iva I. Podgorski, Marijana Popović Hadžija, Ivana Tartaro Bujak, Ana Dekanić, Robert Bagarić, Vladimir Farkaš, Sandra Sobočanec and Tihomir Balog

Antioxidants 2020, 9(2), 174; https://doi.org/10.3390/antiox9020174 - 20 Feb 2020

Cited by 8 | Viewed by 5787

Abstract

Metabolic homeostasis is differently regulated in males and females. Little is known about the mitochondrial Sirtuin 3 (Sirt3) protein in the context of sex-related differences in the development of metabolic dysregulation. To test our hypothesis that the role of Sirt3 in response to [...] Read more.

Metabolic homeostasis is differently regulated in males and females. Little is known about the mitochondrial Sirtuin 3 (Sirt3) protein in the context of sex-related differences in the development of metabolic dysregulation. To test our hypothesis that the role of Sirt3 in response to a high-fat diet (HFD) is sex-related, we measured metabolic, antioxidative, and mitochondrial parameters in the liver of Sirt3 wild-type (WT) and knockout (KO) mice of both sexes fed with a standard or HFD for ten weeks. We found that the combined effect of Sirt3 and an HFD was evident in more parameters in males (lipid content, glucose uptake, pparγ, cyp2e1, cyp4a14, Nrf2, MnSOD activity) than in females (protein damage and mitochondrial respiration), pointing towards a higher reliance of males on the effect of Sirt3 against HFD-induced metabolic dysregulation. The male-specific effects of an HFD also include reduced Sirt3 expression in WT and alleviated lipid accumulation and reduced glucose uptake in KO mice. In females, with a generally higher expression of genes involved in lipid homeostasis, either the HFD or Sirt3 depletion compromised mitochondrial respiration and increased protein oxidative damage. This work presents new insights into sex-related differences in the various physiological parameters with respect to nutritive excess and Sirt3. Full article

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

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19 pages, 1823 KiB

Open AccessArticle

The Association of Ascorbic Acid, Deferoxamine and N-Acetylcysteine Improves Cardiac Fibroblast Viability and Cellular Function Associated with Tissue Repair Damaged by Simulated Ischemia/Reperfusion

by Pablo Parra-Flores, Jaime A Riquelme, Paula Valenzuela-Bustamante, Sebastian Leiva-Navarrete, Raúl Vivar, Jossete Cayupi-Vivanco, Esteban Castro, Claudio Espinoza-Pérez, Felipe Ruz-Cortés, Zully Pedrozo, Sergio Lavandero, Ramon Rodrigo and Guillermo Diaz-Araya

Antioxidants 2019, 8(12), 614; https://doi.org/10.3390/antiox8120614 - 03 Dec 2019

Cited by 18 | Viewed by 5156

Abstract

Acute myocardial infarction is one of the leading causes of death worldwide and thus, an extensively studied disease. Nonetheless, the effects of ischemia/reperfusion injury elicited by oxidative stress on cardiac fibroblast function associated with tissue repair are not completely understood. Ascorbic acid, deferoxamine, [...] Read more.

Acute myocardial infarction is one of the leading causes of death worldwide and thus, an extensively studied disease. Nonetheless, the effects of ischemia/reperfusion injury elicited by oxidative stress on cardiac fibroblast function associated with tissue repair are not completely understood. Ascorbic acid, deferoxamine, and N-acetylcysteine (A/D/N) are antioxidants with known cardioprotective effects, but the potential beneficial effects of combining these antioxidants in the tissue repair properties of cardiac fibroblasts remain unknown. Thus, the aim of this study was to evaluate whether the pharmacological association of these antioxidants, at low concentrations, could confer protection to cardiac fibroblasts against simulated ischemia/reperfusion injury. To test this, neonatal rat cardiac fibroblasts were subjected to simulated ischemia/reperfusion in the presence or absence of A/D/N treatment added at the beginning of simulated reperfusion. Cell viability was assessed using trypan blue staining, and intracellular reactive oxygen species (ROS) production was assessed using a 2′,7′-dichlorofluorescin diacetate probe. Cell death was measured by flow cytometry using propidium iodide. Cell signaling mechanisms, differentiation into myofibroblasts and pro-collagen I production were determined by Western blot, whereas migration was evaluated using the wound healing assay. Our results show that A/D/N association using a low concentration of each antioxidant increased cardiac fibroblast viability, but that their separate administration did not provide protection. In addition, A/D/N association attenuated oxidative stress triggered by simulated ischemia/reperfusion, induced phosphorylation of pro-survival extracellular-signal-regulated kinases 1/2 (ERK1/2) and PKB (protein kinase B)/Akt, and decreased phosphorylation of the pro-apoptotic proteins p38- mitogen-activated protein kinase (p38-MAPK) and c-Jun-N-terminal kinase (JNK). Moreover, treatment with A/D/N also reduced reperfusion-induced apoptosis, evidenced by a decrease in the sub-G1 population, lower fragmentation of pro-caspases 9 and 3, as well as increased B-cell lymphoma-extra large protein (Bcl-xL)/Bcl-2-associated X protein (Bax) ratio. Furthermore, simulated ischemia/reperfusion abolished serum-induced migration, TGF-β1 (transforming growth factor beta 1)-mediated cardiac fibroblast-to-cardiac myofibroblast differentiation, and angiotensin II-induced pro-collagen I synthesis, but these effects were prevented by treatment with A/D/N. In conclusion, this is the first study where a pharmacological combination of A/D/N, at low concentrations, protected cardiac fibroblast viability and function after simulated ischemia/reperfusion, and thereby represents a novel therapeutic approach for cardioprotection. Full article

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

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Review

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26 pages, 1022 KiB

Open AccessReview

When Oxidative Stress Meets Epigenetics: Implications in Cancer Development

by Álvaro García-Guede, Olga Vera and Inmaculada Ibáñez-de-Caceres

Antioxidants 2020, 9(6), 468; https://doi.org/10.3390/antiox9060468 - 01 Jun 2020

Cited by 35 | Viewed by 4673

Abstract

Cancer is one of the leading causes of death worldwide and it can affect any part of the organism. It arises as a consequence of the genetic and epigenetic changes that lead to the uncontrolled growth of the cells. The epigenetic machinery can [...] Read more.

Cancer is one of the leading causes of death worldwide and it can affect any part of the organism. It arises as a consequence of the genetic and epigenetic changes that lead to the uncontrolled growth of the cells. The epigenetic machinery can regulate gene expression without altering the DNA sequence, and it comprises methylation of the DNA, histones modifications, and non-coding RNAs. Alterations of these gene-expression regulatory elements can be produced by an imbalance of the intracellular environment, such as the one derived by oxidative stress, to promote cancer development, progression, and resistance to chemotherapeutic treatments. Here we review the current literature on the effect of oxidative stress in the epigenetic machinery, especially over the largely unknown ncRNAs and its consequences toward cancer development and progression. Full article

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

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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 11437

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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17 pages, 909 KiB

Open AccessReview

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

by Lourdes Alvarez-Arellano, Nadia González-García, Marcela Salazar-García and Juan Carlos Corona

Antioxidants 2020, 9(2), 176; https://doi.org/10.3390/antiox9020176 - 21 Feb 2020

Cited by 37 | Viewed by 18769

Abstract

Psychostimulants and non-psychostimulants are the medications prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). However, several adverse results have been linked with an increased risk of substance use and side effects. The pathophysiology of ADHD is not completely known, although it has been [...] Read more.

Psychostimulants and non-psychostimulants are the medications prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). However, several adverse results have been linked with an increased risk of substance use and side effects. The pathophysiology of ADHD is not completely known, although it has been associated with an increase in inflammation and oxidative stress. This review presents an overview of findings following antioxidant treatment for ADHD and describes the potential amelioration of inflammation and oxidative stress using antioxidants that might have a future as multi-target adjuvant therapy in ADHD. The use of antioxidants against inflammation and oxidative conditions is an emerging field in the management of several neurodegenerative and neuropsychiatric disorders. Thus, antioxidants could be promising as an adjuvant ADHD therapy. Full article

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

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39 pages, 10783 KiB

Open AccessReview

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

by María Luisa Castejón, Tatiana Montoya, Catalina Alarcón-de-la-Lastra and Marina Sánchez-Hidalgo

Antioxidants 2020, 9(2), 149; https://doi.org/10.3390/antiox9020149 - 10 Feb 2020

Cited by 82 | Viewed by 8415

Abstract

Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, [...] Read more.

Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae and Pedialaceae, among others. Specifically, Olea europaea L. (Oleaceae) is rich in oleuropein (OL), dimethyl-OL, and ligstroside secoiridoids, and their hydrolysis derivatives are mostly OL-aglycone, oleocanthal (OLE), oleacein (OLA), elenolate, oleoside-11-methyl ester, elenoic acid, hydroxytyrosol (HTy), and tyrosol (Ty). These compounds have proved their efficacy in the management of diabetes, cardiovascular and neurodegenerative disorders, cancer, and viral and microbial infections. Particularly, the antioxidant, anti-inflammatory, and immunomodulatory properties of secoiridoids from the olive tree (Olea europaea L. (Oleaceae)) have been suggested as a potential application in a large number of inflammatory and reactive oxygen species (ROS)-mediated diseases. Thus, the purpose of this review is to summarize recent advances in the protective role of secoiridoids derived from the olive tree (preclinical studies and clinical trials) in diseases with an important pathogenic contribution of oxidative and peroxidative stress and damage, focusing on their plausible mechanisms of the action involved. Full article

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

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20 pages, 2072 KiB

Open AccessReview

Glucose as a Major Antioxidant: When, What for and Why It Fails?

by Andriy Cherkas, Serhii Holota, Tamaz Mdzinarashvili, Rosita Gabbianelli and Neven Zarkovic

Antioxidants 2020, 9(2), 140; https://doi.org/10.3390/antiox9020140 - 05 Feb 2020

Cited by 62 | Viewed by 13457

Abstract

A human organism depends on stable glucose blood levels in order to maintain its metabolic needs. Glucose is considered to be the most important energy source, and glycolysis is postulated as a backbone pathway. However, when the glucose supply is limited, ketone bodies [...] Read more.

A human organism depends on stable glucose blood levels in order to maintain its metabolic needs. Glucose is considered to be the most important energy source, and glycolysis is postulated as a backbone pathway. However, when the glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of the pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. The PPP generates and maintains the levels of nicotinamide adenine dinucleotide phosphate (NADPH) needed for the reduction in oxidized glutathione and protein thiols, the synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. The flux of glucose into a PPP—particularly under extreme oxidative and toxic challenges—is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP⁺ that is required for the activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain the disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload, and provide new insights into the positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis. Full article

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

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16 pages, 2513 KiB

Open AccessReview

The Influence of Light on Reactive Oxygen Species and NF-кB in Disease Progression

by Naresh Kumar Rajendran, Blassan P. George, Rahul Chandran, Ivan Mfouo Tynga, Nicolette Houreld and Heidi Abrahamse

Antioxidants 2019, 8(12), 640; https://doi.org/10.3390/antiox8120640 - 12 Dec 2019

Cited by 53 | Viewed by 5155

Abstract

Reactive oxygen species (ROS) are important secondary metabolites that play major roles in signaling pathways, with their levels often used as analytical tools to investigate various cellular scenarios. They potentially damage genetic material and facilitate tumorigenesis by inhibiting certain tumor suppressors. In diabetic [...] Read more.

Reactive oxygen species (ROS) are important secondary metabolites that play major roles in signaling pathways, with their levels often used as analytical tools to investigate various cellular scenarios. They potentially damage genetic material and facilitate tumorigenesis by inhibiting certain tumor suppressors. In diabetic conditions, substantial levels of ROS stimulate oxidative stress through specialized precursors and enzymatic activity, while minimum levels are required for proper wound healing. Photobiomodulation (PBM) uses light to stimulate cellular mechanisms and facilitate the removal of oxidative stress. Photodynamic therapy (PDT) generates ROS to induce selective tumor destruction. The regulatory roles of PBM via crosstalk between ROS and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) are substantial for the appropriate management of various conditions. Full article

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

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