Oxidative stress and aging – the use of superoxide dismutase/catalase mimetics to extend lifespan

2003 ◽  
Vol 31 (6) ◽  
pp. 1305-1307 ◽  
Author(s):  
J.N. Sampayo ◽  
M.S. Gill ◽  
G.J. Lithgow
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Pharmacological Intervention ◽  
Protective Effects ◽  
C Elegans ◽  
Compound Libraries ◽  
Novel Drugs ◽  
The Face ◽  
Underlying Mechanisms ◽  
High Throughput Screens

To date, more than 40 genes have been identified in the nematode Caenorhabditis elegans, which, when mutated, lead to an increase in lifespan. Of those tested, all confer an increased resistance to oxidative stress. In addition, the lifespan of C. elegans can also be extended by the administration of synthetic superoxide dismutase/catalase mimetics. These compounds also appear to confer resistance to oxidative damage, since they protect against paraquat treatment. The protective effects of these compounds are apparent with treatment during either development or adulthood. These findings have demonstrated that pharmacological intervention in the aging process is possible and that these compounds can provide important information about the underlying mechanisms. To date, such interventions have targeted known processes rather than screening compound libraries because of the limitations of assessing lifespan in nematodes. However, we have recently developed a microplate-based assay that allows for a rapid and objective score of nematode survival at rates many times higher than previously possible. This system now provides the opportunity to perform high-throughput screens for compounds that affect nematode survival in the face of acute oxidative stress and will facilitate the identification of novel drugs that extend nematode lifespan.

Diazoxide Modulates Cardiac Hypertrophy by Targeting H2O2 Generation and Mitochondrial Superoxide Dismutase Activity

2020 ◽  
Vol 13 (1) ◽  
pp. 76-83
Author(s):  
Aline Maria Brito Lucas ◽  
Joana Varlla de Lacerda Alexandre ◽  
Maria Thalyne Silva Araújo ◽  
Cicera Edna Barbosa David ◽  
Yuana Ivia Ponte Viana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Cardiac Hypertrophy ◽  
Superoxide Dismutase Activity ◽  
Heart Weight ◽  
Pharmacological Intervention ◽  
Wall Thickening ◽  
H2o2 Production ◽  
Mitochondrial Superoxide ◽  
Mitochondrial Superoxide Dismutase

Background: Cardiac hypertrophy involves marked wall thickening or chamber enlargement. If sustained, this condition will lead to dysfunctional mitochondria and oxidative stress. Mitochondria have ATP-sensitive K+ channels (mitoKATP) in the inner membrane that modulate the redox status of the cell. Objective: We investigated the in vivo effects of mitoKATP opening on oxidative stress in isoproterenol- induced cardiac hypertrophy. Methods: Cardiac hypertrophy was induced in Swiss mice treated intraperitoneally with isoproterenol (ISO - 30 mg/kg/day) for 8 days. From day 4, diazoxide (DZX - 5 mg/kg/day) was used in order to open mitoKATP (a clinically relevant therapy scheme) and 5-hydroxydecanoate (5HD - 5 mg/kg/day) or glibenclamide (GLI - 3 mg/kg/day) were used as mitoKATP blockers. Results: Isoproterenol-treated mice had elevated heart weight/tibia length ratios (HW/TL). Additionally, hypertrophic hearts had elevated levels of carbonylated proteins and Thiobarbituric Acid Reactive Substances (TBARS), markers of protein and lipid oxidation. In contrast, mitoKATP opening with DZX avoided ISO effects on gross hypertrophic markers (HW/TL), carbonylated proteins and TBARS, in a manner reversed by 5HD and GLI. Moreover, DZX improved mitochondrial superoxide dismutase activity. This effect was also blocked by 5HD and GLI. Additionally, ex vivo treatment of isoproterenol- induced hypertrophic cardiac tissue with DZX decreased H2O2 production in a manner sensitive to 5HD, indicating that this drug also acutely avoids oxidative stress. Conclusion: Our results suggest that diazoxide blocks oxidative stress and reverses cardiac hypertrophy. This pharmacological intervention could be a potential therapeutic strategy to prevent oxidative stress associated with cardiac hypertrophy.

scholarly journals Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1076
Author(s):  
Guoyi Tang ◽  
Yu Xu ◽  
Cheng Zhang ◽  
Ning Wang ◽  
Huabin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Green Tea ◽  
Liver Diseases ◽  
Randomized Clinical Trials ◽  
Epigallocatechin Gallate ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver Diseases ◽  
Underlying Mechanisms

Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD.

Protective Effects of Ginsenosides on 17α-Ethynyelstradiol-Induced Intrahepatic Cholestasis via Anti-Oxidative and Anti-Inflammatory Mechanisms in Rats

2017 ◽  
Vol 45 (08) ◽  
pp. 1613-1629 ◽  
Author(s):  
Yan-Jiao Xu ◽  
Zao-Qin Yu ◽  
Cheng-Liang Zhang ◽  
Xi-Ping Li ◽  
Cheng-Yang Feng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alkaline Phosphatase ◽  
Superoxide Dismutase ◽  
Protein Expression ◽  
Intrahepatic Cholestasis ◽  
Serum Levels ◽  
Total Bile Acid ◽  
Protective Effects ◽  
Sod Activity ◽  
Mda Content

The present study was designed to assess the effects and potential mechanisms of ginsenosides on 17[Formula: see text]-ethynyelstradiol (EE)-induced intrahepatic cholestasis (IC). Ginsenoside at doses of 30, 100, 300[Formula: see text]mg/kg body weight was intragastrically (i.g.) given to rats for 5 days to examine the effect on EE-induced IC. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bile acid (TBA) were measured. Hepatic malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined. Protein expression of proinflammatory cytokines TNF-[Formula: see text], IL-6 and IL-1[Formula: see text] was analyzed by immunohistochemistry and Western blot. Results indicated that ginsenosides remarkably prevented EE-induced increase in the serum levels of AST, ALT, ALP and TBA. Moreover, the elevation of hepatic MDA content induced by EE was significantly reduced, while hepatic SOD activities were significantly increased when treated with ginsenosides. Histopathology of the liver tissue showed that pathological injuries were relieved after treatment with ginsenosides. In addition, treatment with ginsenosides could significantly downregulate the protein expression of TNF-[Formula: see text], IL-6 and IL-1[Formula: see text] compared with EE group. These findings indicate that ginsenosides exert the hepatoprotective effect on EE-induced intrahepatic cholestasis in rats, and this protection might be attributed to the attenuation of oxidative stress and inflammation.

scholarly journals The effect of intrinsic physiological traits on diapause survival and their underlying mechanisms in an annual bee species Bombus impatiens

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Erin Treanore ◽  
Etya Amsalem
Keyword(s):  
Oxidative Stress ◽  
Life Stage ◽  
Mass Gain ◽  
Nutrient Acquisition ◽  
Bombus Impatiens ◽  
Factors Affecting ◽  
Age Related ◽  
The Face ◽  
Underlying Mechanisms ◽  
Age Range

Abstract In the face of insect declines, identifying phases of the life cycle when insects are particularly vulnerable to mortality is critical to conservation efforts. For numerous annual insect groups, diapause is both a key adaptation that allows survival of inhospitable conditions and a physiologically demanding life stage that can result in high rates of mortality. As bees continue to garner attention as a group experiencing high rates of decline, improving our understanding of how annual bees prepare for diapause and identifying factors that reduce survival is imperative. Here, we studied factors affecting diapause survival length and their underlying mechanisms using an economically and ecologically important annual bee species, Bombus impatiens. We examined how age and mass upon diapause onset correlate with diapause survival length, and the mechanistic role of nutrient acquisition and oxidative stress post pupal eclosion in mediating these effects. Our findings show that both age and mass were strong predictors of diapause survival length. Heavier queens or queens in the age range of ~6–17 days survived longer in diapause. Mass gain was attributed to increases in lipid, protein and glycerol amounts following pupal eclosion, and the ability to deal with oxidative stress was significantly compromised in older pre-diapause queens. Our results demonstrate that age-related shifts in bee physiology and timing of nutrient acquisition may both be critical factors driving diapause survival.

scholarly journals Lipopolysaccharide exposure induces oxidative damage in Caenorhabditis elegans: protective effects of carnosine

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Ma ◽  
Xiaoyuan Xu ◽  
Ranran Wang ◽  
Haijing Yan ◽  
Huijuan Yao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Protective Effects ◽  
Related Gene ◽  
Rt Pcr ◽  
C Elegans ◽  
Apoptosis Related Gene

Abstract Background The present study was designed to investigate the protective effects and mechanisms of carnosine on lipopolysaccharide (LPS)-induced injury in Caenorhabditis elegans. Methods C. elegans individuals were stimulated for 24 h with LPS (100 μg/mL), with or without carnosine (0.1, 1, 10 mM). The survival rates and behaviors were determined. The activities of superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) were determined using the respective kits. Reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the differential expression of sod-1, sod-2, sod-3, daf-16, ced-3, ced-9, sek-1, and pmk-1. Western blotting was used to determine the levels of SEK1, p38 mitogen-activated protein kinase (MAPK), cleaved caspase3, and Bcl-2. C. elegans sek-1 (km2) mutants and pmk-1 (km25) mutants were used to elucidate the role of the p38 MAPK signaling pathway. Results Carnosine improved the survival of LPS-treated C. elegans and rescued behavioral phenotypes. It also restrained oxidative stress by decreasing MDA levels and increasing SOD, GR, CAT, and GSH levels. RT-PCR results showed that carnosine treatment of wild-type C. elegans up-regulated the mRNA expression of the antioxidant-related genes sod-1, sod-2, sod-3, and daf-16. The expression of the anti-apoptosis-related gene ced-9 and apoptosis-related gene ced-3 was reversed by carnosine. In addition, carnosine treatment significantly decreased cleaved caspase3 levels and increased Bcl-2 levels in LPS-treated C. elegans. Apoptosis in the loss-of-function strains of the p38 MAPK signaling pathway was suppressed under LPS stress; however, the apoptotic effects of LPS were blocked in the sek-1 and pmk-1 mutants. The expression levels of sek-1 and pmk-1 mRNAs were up-regulated by LPS and reversed by carnosine. Finally, the expression of p-p38MAPK and SEK1 was significantly increased by LPS, which was reversed by carnosine. Conclusion Carnosine treatment protected against LPS injury by decreasing oxidative stress and inhibiting apoptosis through the p38 MAPK pathway.

scholarly journals Fine Particulate Matter Leads to Unfolded Protein Response and Shortened Lifespan by Inducing Oxidative Stress in C. elegans

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yunli Zhao ◽  
Ling Jin ◽  
Yuxin Chi ◽  
Jing Yang ◽  
Quan Zhen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Particulate Matter ◽  
Fine Particulate Matter ◽  
Metabolic Enzyme ◽  
C Elegans ◽  
Unfolded Protein ◽  
Fine Particulate ◽  
Underlying Mechanisms ◽  
Protein Response ◽  
Phenylbutyric Acid

Oxidative stress has been proven as one of the most critical regulatory mechanisms involved in fine Particulate Matter- (PM2.5-) mediated toxicity. For a better understanding of the underlying mechanisms that enable oxidative stress to participate in PM2.5-induced toxic effects, the current study explored the effects of oxidative stress induced by PM2.5 on UPR and lifespan in C. elegans. The results implicated that PM2.5 exposure induced oxidative stress response, enhanced metabolic enzyme activity, activated UPR, and shortened the lifespan of C. elegans. Antioxidant N-acetylcysteine (NAC) could suppress the UPR through reducing the oxidative stress; both the antioxidant NAC and UPR inhibitor 4-phenylbutyric acid (4-PBA) could rescue the lifespan attenuation caused by PM2.5, indicating that the antioxidant and moderate proteostasis contribute to the homeostasis and adaptation to oxidative stress induced by PM2.5.

scholarly journals Cardiac Electrophysiological Alterations in Heart/Muscle-Specific Manganese-Superoxide Dismutase-Deficient Mice: Prevention by a Dietary Antioxidant Polyphenol

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Tadahiro Sunagawa ◽  
Takahiko Shimizu ◽  
Akio Matsumoto ◽  
Motoyuki Tagashira ◽  
Tomomasa Kanda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Action Potential ◽  
Heart Muscle ◽  
Chronic Exposure ◽  
Manganese Superoxide Dismutase ◽  
Left Ventricular ◽  
Protective Effects ◽  
Manganese Superoxide ◽  
Dietary Antioxidant

Cardiac electrophysiological alterations induced by chronic exposure to reactive oxygen species and protective effects of dietary antioxidant have not been thoroughly examined. We recorded surface electrocardiograms (ECG) and evaluated cellular electrophysiological abnormalities in enzymatically-dissociated left ventricular (LV) myocytes in heart/muscle-specific manganese-superoxide dismutase-deficient (H/M-Sod2−/−) mice, which exhibit dilated cardiomyopathy due to increased oxidative stress. We also investigated the influences of intake of apple polyphenols (AP) containing mainly procyanidins with potent antioxidant activity. The QRS and QT intervals of ECG recorded in H/M-Sod2−/−mice were prolonged. The effective refractory period in the LV myocardium of H/M-Sod2−/−mice was prolonged, and susceptibility to ventricular tachycardia or fibrillation induced by rapid ventricular pacing was increased. Action potential duration in H/M-Sod2−/−LV myocytes was prolonged, and automaticity was enhanced. The density of the inwardly rectifier K+current (IK1) was decreased in the LV cells of H/M-Sod2−/−mice. The AP intake partially improved these electrophysiological alterations and extended the lifespan in H/M-Sod2−/−mice. Thus, chronic exposure of the heart to oxidative stress produces a variety of electrophysiological abnormalities, increased susceptibility to ventricular arrhythmias, and action potential changes associated with the reduced density ofIK1. Dietary intake of antioxidant nutrients may prevent oxidative stress-induced electrophysiological disturbances.

scholarly journals Daphnetin Attenuated Cisplatin-Induced Acute Nephrotoxicity With Enhancing Antitumor Activity of Cisplatin by Upregulating SIRT1/SIRT6-Nrf2 Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoye Fan ◽  
Wei Wei ◽  
Jingbo Huang ◽  
Liping Peng ◽  
Xinxin Ci
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cell Damage ◽  
Protective Effects ◽  
Normal Tissues ◽  
Nrf2 Signaling Pathway ◽  
Apoptosis Pathways ◽  
Underlying Mechanisms

Cisplatin (CDDP) is a widely used drug for cancer treatment that exhibits major side effects in normal tissues, such as nephrotoxicity in kidneys. The Nrf2 signaling pathway, a regulator of mitochondrial dysfunction, oxidative stress and inflammation, is a potential therapeutic target in CDDP-induced nephrotoxicity. We explored the underlying mechanisms in wild-type (WT) and Nrf2−/− mice on CDDP-induced renal dysfunction in vivo. We found that Nrf2 deficiency aggravated CDDP-induced nephrotoxicity, and Daph treatment significantly ameliorated the renal injury characterized by biochemical markers in WT mice and reduced the CDDP-induced cell damage. In terms of the mechanism, Daph upregulated the SIRT1 and SIRT6 expression in vivo and in vitro. Furthermore, Daph inhibited the expression level of NOX4, whereas it activated Nrf2 translocation and antioxidant enzymes HO-1 and NQO1, and alleviated oxidative stress and mitochondrial dysfunction. Moreover, Daph suppressed CDDP-induced NF-κB and MAPK inflammation pathways, as well as p53 and cleaved caspase-3 apoptosis pathways. Notably, the protective effects of Daph in WT mice were completely abrogated in Nrf2−/− mice. Moreover, Daph enhanced, rather than attenuated, the tumoricidal effect of CDDP.

scholarly journals GLP-1(9-36), a GLP-1 cleavage product, protects against oxidative stress and apoptosis through PI3K/Akt/NOS pathway in H9c2 cardiomyoblasts

2021 ◽  
Author(s):  
Narawat Nuamnaichati ◽  
Warisara Parichatikanond ◽  
Supachoke Mangmool
Keyword(s):  
Oxidative Stress ◽  
Active Form ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Protective Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Akt Phosphorylation ◽  
H9c2 Cardiomyoblasts ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Abstract GLP-1(7–36), a major active form of GLP-1 hormone, is rapidly cleaved by dipeptidyl peptidase-4 to generate a truncated metabolite, GLP-1(9–36) which has a low affinity for GLP-1 receptor (GLP-1R). GLP-1(7–36) has been shown to have protective effects on cardiovascular system through GLP-1R-dependent way. Nevertheless, the cardioprotective effects of GLP-1(9–36) have not fully understood. The present study investigated the effects of GLP-1(9–36), including its underlying mechanisms against oxidative stress and apoptosis in H9c2 cardiomyoblasts. Here, we reported that GLP-1(9–36) protects H9c2 cardiomyoblasts from hydrogen peroxide (H2O2)-induced oxidative stress by promoting the synthesis of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1. In addition, treatment with GLP-1(9–36) suppressed H2O2-induced apoptosis by attenuating caspase-3 activity and upregulating proapoptotic proteins, Bcl-2 and Bcl-xL. These protective effects of GLP-1(9–36) are attenuated by blockade of PI3K-mediated Akt phosphorylation and prevention of nitric oxide synthase (NOS)-induced NO production. Collectively, GLP-1(9–36) represents the potential therapeutic target for prevention of oxidative stress and apoptosis in the heart.

scholarly journals N-Acetyl Serotonin Alleviates Oxidative Damage by Activating Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Porcine Enterocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 303
Author(s):  
Haiwei Liang ◽  
Ning Liu ◽  
Renjie Wang ◽  
Yunchang Zhang ◽  
Jingqing Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gastrointestinal Diseases ◽  
Mucosal Barrier ◽  
Related Factor ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Downstream Target ◽  
Underlying Mechanisms ◽  
And Function

Apoptosis of intestinal epithelial cells following oxidative stress is a major cause of mucosal barrier dysfunction and is associated with the pathogenesis of various gastrointestinal diseases. Although L-tryptophan (Trp) is known to improve intestinal integrity and function, a beneficial effect of N-acetyl serotonin (NAS), a metabolite of Trp, on the apoptosis of enterocytes and the underlying mechanisms remain largely unknown. In the present study, we showed that porcine enterocytes treated with 4-hydroxy-2-nonenal (4-HNE), a metabolite of lipid peroxidation, led to upregulation of apoptotic proteins, including Bax and cleaved caspase-3, and reduction of tight junction proteins. These effects of 4-HNE were significantly abrogated by NAS. In addition, NAS reduced ROS accumulation while increasing the intracellular concentration of glutathione (GSH), and the abundance of the Nrf2 protein in the nucleus and its downstream target proteins. Importantly, these protective effects of NAS were abrogated by Atra, an inhibitor of Nrf2, indicating a dependence on Nrf2 signaling. Taken together, we demonstrated that NAS attenuated oxidative stress-induced cellular injury in porcine enterocytes by regulating Nrf2 signaling. These findings provide new insights into a functional role of NAS in maintaining intestinal homeostasis.

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