Protective effects of melatonin and N-acetyl cysteine against oxidative stress induced by microcystin-LR on cardiac muscle tissue

Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A-KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625—1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide-treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism.

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The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction?

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00890.2005 ◽

2006 ◽

Vol 291 (4) ◽

pp. R927-R935 ◽

Cited By ~ 55

Author(s):

Susanne Rohrbach ◽

Stefanie Gruenler ◽

Mirja Teschner ◽

Juergen Holtz

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Cardiac Muscle ◽

Caloric Restriction ◽

Dna Cleavage ◽

Thioredoxin Reductase ◽

Protective Effects ◽

Young Rats ◽

Age Related ◽

Thioredoxin System

Cellular redox balance is maintained by various antioxidative systems. Among those is the thioredoxin system, consisting of thioredoxin, thioredoxin reductase, and NADPH. In the present study, we examined the effects of caloric restriction (2 mo) on the expression of the cytosolic and mitochondrial thioredoxin system in skeletal muscle and heart of senescent and young rats. Mitochondrial thioredoxin reductase (TrxR2) is significantly reduced in aging skeletal and cardiac muscle and renormalized after caloric restriction, while the cytosolic isoform remains unchanged. Thioredoxins (mitochondrial Trx2, cytosolic Trx1) are not influenced by caloric restriction. In skeletal and cardiac muscle of young rats, caloric restriction has no effect on the expression of thioredoxins or thioredoxin reductases. Enforced reduction of TrxR2 (small interfering RNA) in myoblasts under exposure to ceramide or TNF-α causes a dramatic enhancement of nucleosomal DNA cleavage, caspase 9 activation, and mitochondrial reactive oxygen species release, together with reduced cell viability, while this TrxR2 reduction is without effect in unstimulated myoblasts under basal conditions. Oxidative stress in vitro (H2O2in C2C12myoblasts and myotubes) results in different changes: TrxR2, Trx2, and Trx1 are induced without alterations in the cytosolic thioredoxin reductase isoforms. Thus aging is associated with a TrxR2 reduction in skeletal muscle and heart, which enhances susceptibility to apoptotic stimuli but is renormalized after short-term caloric restriction. Exogenous oxidative stress does not result in these age-related changes of TrxR2.

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Bilobalide protects against ischemia/reperfusion-induced oxidative stress and inflammatory responses via the MAPK/NF-κB pathways in rats

BMC Musculoskeletal Disorders ◽

10.1186/s12891-020-03479-9 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Ying Li ◽

Jiliang Jiang ◽

Liangcheng Tong ◽

Tingting Gao ◽

Lei Bai ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Reperfusion Injury ◽

Muscle Tissue ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Weight Ratio ◽

Dry Weight ◽

Protective Effects

Abstract Background Clinically, skeletal muscle ischemia/reperfusion injury is a life-threatening syndrome that is often caused by skeletal muscle damage and is characterized by oxidative stress and inflammatory responses. Bilobalide has been found to have antioxidative and anti-inflammatory effects. However, it is unclear whether bilobalide can protect skeletal muscle from ischemia/reperfusion injury. Methods The effects of bilobalide on ischemia/reperfusion-injured skeletal muscle were investigated by performing hematoxylin and eosin staining and assessing the wet weight/dry weight ratio of muscle tissue. Then, we measured lipid peroxidation, antioxidant activity and inflammatory cytokine levels. Moreover, Western blotting was conducted to examine the protein levels of MAPK/NF-κB pathway members. Results Bilobalide treatment could protected hind limb skeletal muscle from ischemia/reperfusion injury by alleviating oxidative stress and inflammatory responses via the MAPK/NF-κB pathways. Conclusions Bilobalide may be a promising drug for I/R-injured muscle tissue. However, the specific mechanisms for the protective effects still need further study.

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Protective effects of N-acetyl cysteine with zinc and selenium on chronic mercury induced oxidative stress and DNA damage evaluation in rats

Toxicology Letters ◽

10.1016/j.toxlet.2013.05.182 ◽

2013 ◽

Vol 221 ◽

pp. S112

Author(s):

Deepmala Joshi ◽

Deepak Kumar Mittal

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Damage Evaluation ◽

Protective Effects ◽

Acetyl Cysteine

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Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation

Antioxidants ◽

10.3390/antiox9090774 ◽

2020 ◽

Vol 9 (9) ◽

pp. 774

Author(s):

Silvia Nistri ◽

Claudia Fiorillo ◽

Matteo Becatti ◽

Daniele Bani

Keyword(s):

Oxidative Stress ◽

Cardiac Muscle ◽

Reduced Glutathione ◽

Cell Damage ◽

Antioxidant Properties ◽

Muscle Cells ◽

Protective Effects ◽

Cardiac Muscle Cells ◽

Relaxin 2

Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis. These effects appear to rely on the up-regulation of the cellular availability of reduced glutathione (GSH), a ubiquitous endogenous antioxidant metabolite. Conversely, superoxide dismutase activity was not influenced by RLX, which, however, was not endowed with chemical antioxidant properties. Taken together, these findings verify the major pharmacological role of RLX in the protection against HR-induced oxidative stress, and shed first light on its mechanisms of action.

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Protective Effects of α-Tocopherol and N-Acetyl-Cysteine on Diazinon-Induced Oxidative Stress and Acetylcholinesterase Inhibition in Rats

Toxicology Mechanisms and Methods ◽

10.1080/15376510600860318 ◽

2007 ◽

Vol 17 (2) ◽

pp. 109-115 ◽

Cited By ~ 38

Author(s):

Shahin Shadnia ◽

Mojgan Dasgar ◽

Sepideh Taghikhani ◽

Azadeh Mohammadirad ◽

Reza Khorasani ◽

...

Keyword(s):

Oxidative Stress ◽

Acetylcholinesterase Inhibition ◽

Protective Effects ◽

Acetyl Cysteine

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Drug-Induced Liver Injury: Clinical Evidence of N-Acetyl Cysteine Protective Effects

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/3320325 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yonela Ntamo ◽

Khanyisani Ziqubu ◽

Nireshni Chellan ◽

Bongani B. Nkambule ◽

Tawanda M. Nyambuya ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Hepatic Injury ◽

Clinical Evidence ◽

Antioxidant Properties ◽

Pathological Feature ◽

Protective Effects ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Acetyl Cysteine

Oxidative stress is a key pathological feature implicated in both acute and chronic liver diseases, including drug-induced liver injury (DILI). The latter describes hepatic injury arising as a direct toxic effect of administered drugs or their metabolites. Although still underreported, DILI remains a significant cause of liver failure, especially in developed nations. Currently, it is understood that mitochondrial-generated oxidative stress and abnormalities in phase I/II metabolism, leading to glutathione (GSH) suppression, drive the onset of DILI. N-Acetyl cysteine (NAC) has attracted a lot of interest as a therapeutic agent against DILI because of its strong antioxidant properties, especially in relation to enhancing endogenous GSH content to counteract oxidative stress. Thus, in addition to updating information on the pathophysiological mechanisms implicated in oxidative-induced hepatic injury, the current review critically discusses clinical evidence on the protective effects of NAC against DILI, including the reduction of patient mortality. Besides injury caused by paracetamol, NAC can also improve liver function in relation to other forms of liver injury such as those induced by excessive alcohol intake. The implicated therapeutic mechanisms of NAC extend from enhancing hepatic GSH levels to reducing biomarkers of paracetamol toxicity such as keratin-18 and circulating caspase-cleaved cytokeratin-18. However, there is still lack of evidence confirming the benefits of using NAC in combination with other therapies in patients with DILI.

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