The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine

Moradi, Mohammad; Mojtahedzadeh, Mojtaba; Mandegari, Ali; Soltan-Sharifi, Mohammad Sadegh; Najafi, Atabak; Khajavi, Mohammad Reza; Hajibabayee, Molook; Ghahremani, Mohammad Hossein

doi:10.1016/j.rmed.2008.09.013

Cited by 81 publications

(103 citation statements)

References 44 publications

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“…Randomized, double-blind, placebo-controlled studies concluded that intravenous administration of N-acetyl-cysteine in patients with ARDS reduced the need for ventilatory support and improved systemic oxygenation, but failed to reduce mortality (9,11). More recent studies using higher concentrations of N-acetyl-cysteine in patients with ALI reported that reduction of mortality depended on polymorphisms in the glutathione-S-transferase gene (45). Thus, beneficial effects of N-acetyl-cysteine in human ARDS remain in dispute.…”

Section: Discussionmentioning

confidence: 99%

Ascorbate and Deferoxamine Administration after Chlorine Exposure Decrease Mortality and Lung Injury in Mice

Zarogiannis

Jurkuvenaite²,

Fernandez³

et al. 2011

Am J Respir Cell Mol Biol

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Section: Discussionmentioning

confidence: 99%

Ascorbate and Deferoxamine Administration after Chlorine Exposure Decrease Mortality and Lung Injury in Mice

Zarogiannis

Jurkuvenaite²,

Fernandez³

et al. 2011

Am J Respir Cell Mol Biol

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“…For example, selection of patients based on haptoglobin genotype in diabetic patients treated with vitamin E [239] or glutathione-S-transferase genotype in acute respiratory distress syndrome (ARDS)/acute lung injury patients treated with N-acetylcysteine [240], or apo genotype in over-weight individuals treated with quercetin as a blood pressure-lowering agent [144] could alter the response to antioxidant therapy. The real challenge in this regard, is to establish patient selection methods that can predict who is more likely to benefit from antioxidant therapy [241].…”

Section: C-patients Do Not Equally Benefit From Antioxidant Therapymentioning

confidence: 99%

Clinical and pharmacological aspects of bath salt use: A review of the literature and case reports

Miotto¹,

Striebel²,

Cho

et al. 2013

Drug and Alcohol Dependence

121

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Abstract:Reactive oxygen species (ROS) are widely believed to cause or aggravate several human pathologies such as neurodegenerative diseases, cancer, stroke and many other ailments. Antioxidants are assumed to counteract the harmful effects of ROS and therefore prevent or treat oxidative stress-related diseases. In this report, recent human studies exploring the efficiency of antioxidants in prevention and treatment of various diseases are reviewed. Few antioxidants including edaravone (for ischemic stroke in Japan), Nacetylcysteine (for acetaminophen toxicity), alfa-lipoic acid (for diabetic neuropathy) and some flavonoids (polyphenolic compounds present in dietary plants), such as micronized purified flavonoid fraction (diosmin and hesperidin) and oxerutins (for chronic venous insufficiency) as well as baicalein and catechins (for osteoarthritis) have found accepted clinical use. However, despite much enthusiasm in the 1980s and 1990s, many well-known agents such as antioxidant vitamins and also more recently developed compounds such as nitrones have not successfully passed the scrutiny of clinical trials for prevention and treatment of various diseases. This has given rise to a pessimistic view of antioxidant therapy, however, the evidence from human epidemiological studies about the beneficial effects of dietary antioxidants and preclinical in vitro and animal data are compelling. We have probably wasted too much time on agents like antioxidant vitamins instead of focusing on more disease specific, target-directed, highly bioavailable antioxidants. We here discuss possible reasons for the lack of success in some clinical trials and seek to provide some suggestions to be considered if antioxidant therapy is to succeed as an effective therapeutic strategy.

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“…For instance, individuals with homozygous GSTM1 gene deletions appear to be more susceptible to DNA damage induced by GSTM1 substrates (32) and are more at risk of developing lung adenocarcinoma (7). Preliminary clinical studies also suggest that attenuated GST expression may contribute to ALI (25). Moradi and colleagues (25) showed that GSTM1 polymorphisms were associated with increased mortality in critically ill patients with ALI/ARDS.…”

mentioning

confidence: 99%

Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism

Fletcher

Boshier

Wakabayashi

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism. Am J Physiol Lung Cell Mol Physiol 308: L1274 -L1285, 2015. First published April 10, 2015; doi:10.1152/ajplung.00220.2014.-Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-but not GST-expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD ϩ /NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications.N-acetylcysteine; ethacrynic acid; caffeic acid; reactive oxygen species; viability ACUTE LUNG INJURY (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening inflammatory disorders, which may result from both medical and surgical situations such as sepsis, heart surgery, and lung transplantation (41). Among these, ischemia and reperfusion injury constitutes a unique entity, wherein metabolic and oxygen starvation and subsequent reoxygenation can lead to the release and accumulation of reactive oxygen species (ROS) (4). ROS can directly oxidize and damage DNA, protein, and lipid membranes, inactivate antioxidant enzymes, and enhance expression of proinflammatory genes, ultimately leading to cell injury and apoptosis (11).The glutathione-S-transferase (GST) antioxidant enzymes form a multifunctional superfamily of intracellular isozymes that catalyze the conjugation of reduc...

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The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine

Cited by 81 publications

References 44 publications

Ascorbate and Deferoxamine Administration after Chlorine Exposure Decrease Mortality and Lung Injury in Mice

Ascorbate and Deferoxamine Administration after Chlorine Exposure Decrease Mortality and Lung Injury in Mice

Clinical and pharmacological aspects of bath salt use: A review of the literature and case reports

Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism

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