References

• Whether accidental or intentional, acetaminophen poisoning is not uncommon; in fact, it is the most common drug- induced cause of liver failure. When hepatic glutathione is depleted, the toxic metabolite NAPQI fails to be conjugated and causes hepatic injury. At risk are chronic alcoholics, binge drinkers, patients taking medications that induce the P-450 isoenzyme system, and those with concomitant liver disease. PMID: 10223088
• Our findings suggest that acetaminophen administration selectively depletes (within 2 hr) mitochondrial glutathione, and produces local toxicity by altering membrane permeability and decreasing the efficiency of oxidative phosphorylation. This renders mitochondria more susceptible to oxidative damage… PMID: 8937421
• Toxic doses of paracetamol deplete intracellular GSH and result in cell death by a combination of mechanisms, leading to necrosis and apoptosis, mainly in the liver. In clinical situations characterized by low GSH, the risk of toxicity from therapeutic doses of paracetamol may conceivably be increased. This toxicity has been reported in chronic alcoholics who have low intrahepatic GSH and who may have an induced enzyme system that generates the toxic metabolite of paracetamol. PMID: 11941382

• In one study it was shown that the concentration of glutathione was decreased in red blood cells from male Alzheimer's disease patients compared with age- and gender-matched controls. PMID: 15693022
• It has been observed that Alzheimer's patients show an increased level of plasma TBARS, which indicates a higher free radical oxidation of plasma unsaturated phospholipids, and an increased oxidation of red blood cells glutathione, which indicates oxidative stress in peripheral cells. This latter, glutathione oxidation, was found to correlate statistically with the cognitive status of the patients. PMID: 15051321
• GSH is the most abundant cellular non-protein thiol, serves as an important antioxidant, and has been proposed to be important in the protection of cerebrum from oxidative damage. GSH has been reported to be decreased in cerebrum of aging rodents and humans (Hazelton and Lang 1980; Chen et al. 1989; Ravindranath et al. 1989; Iantomasi et al. 1993; Favilli et al. 1994; Martinez et al. 1995; Liu 2002), and alterations in GSH metabolism have been described in diseased regions of brain from AD patients (Aksenov and Markesbery 2001). Alterations in peripheral GSH metabolism have also been described in patients with mild cognitive impairment and AD. PMID: 15857408
• The most abundant endogenous antioxidant, glutathione, plays a significant role in combating oxidative stress. The ratio of oxidized to reduced glutathione is utilized as a measure of intensity of oxidative stress. Antioxidants have long been considered as an approach to slow down AD progression. PMID: 22015471
• In summary, the cerebral GSH and plasminogen systems are essential biological processes that combat the neurodegenerative processes that occur more significantly with advancing age. With knowledge of the physiopathology of neurodegenerative processes, both of these systems can be pharmacological targets, providing reason for hope of prevention of neurodegenerative diseases such as AD. PMID: 23650462 Read this article.

• Recent evidence suggests that some autistic children may have reduced detoxification capacity and may be under chronic oxidative stress. Based on reports of abnormal methionine and glutathione metabolism in autistic children, it was of interest to examine the same metabolic profile in the parents. The results indicated that parents share similar metabolic deficits in methylation capacity and glutathione dependent antioxidant/detoxification capacity observed in many autistic children. Studies are underway to determine whether the abnormal profile in parents reflects linked genetic polymorphisms in these pathways or whether it simply reflects the chronic stress of coping with an autistic child. PMID: 18512136
• This study looked at the metabolism of autistic children. Impairments in the methylation cycle, a very critical part of our body's functioning, were found. Because of this problem in the methylation cycle, autistic children are predisposed to low glutathione which prevents them from detoxifying normally. It was also found that certain co-enzymes, all non-pharmaceutical, support that cycle. PMID: 15585776
• The induction of NK cell activity by IL-2, IL-15 and glutathione was more pronounced in a subgroup with very low NK cell activity. We conclude that that 45% of a subgroup of children with autism suffers from low NK cell activity, and that low intracellular levels of glutathione, IL-2 and IL-15 may be responsible. PMID: 18929414

• Purpose: We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity. Conclusion: This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.
  PMID: 12177109
• Background: Early clinical trials have suggested that glutathione (GSH) offers protection from the toxic effects of cisplatin. Conclusions: The results demonstrate that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient's quality of life is improved. PMID: 9261526
• Here we report that glutathione (GSH) plays a critical role in activation of apoptosis pathways by CD95 (APO-1/Fas) or anticancer drugs. We conclude that dominant apoptosis resistance depends, at least in part, on intracellular GSH levels, which may affect apoptosis signaling at different compartments, for example, the death receptor or mitochondria. PMID: 15105835
• Glutathione (GSH) is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation. Dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions. These include diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells. Manipulation of the GSH synthetic capacity is an important target in the treatment of many of these disorders. PMID: 18601945
• The results of this study indicate that the use of GSH is a safe new method for high-dose cisplatin administration. This regimen is well-tolerated and very effective in ovarian cancer patients with bulky disease and warrants further evaluation. PMID: 2306797
• These findings suggest that mild iron deficiency and low GSH levels, which are associated with increased oxidative stress, increase the risk of oral cavity cancer. PMID: 18584481
• These findings suggest that GSH is able to attenuate the nephrotoxicity induced by CDDP, not only when administered prior to CDDP (Cisplatin, cis-diamminedichloroplatinum), but also when administered at the same time as or subsequent to CDDP administration, without affecting the anticancer activity of CDDP. Thus, the administration of GSH is a promising approach for attenuating the nephrotoxicity caused by CDDP. PMID: 22895541

• As an antioxidant, glutathione (GSH) is essential for allowing the lymphocyte to express its full potential without being hampered by oxiradical accumulation. It is conceivable that the priority of the immune system for the survival of the host has drawn to this vital area the ever-diminishing GSH precursors, thus depriving the skeletal muscle of adequate GSH precursors to sustain a normal aerobic metabolism resulting in fatigue and eventually myalgia. PMID: 10608272
• The role of oxidative stress in CFS is an important area for current and future research as it suggests the use of antioxidants in the management of CFS. Specifically, the dietary supplements glutathione, N-acetylcysteine, alpha-lipoic acid… may be beneficial. PMID: 11703165

CYSTIC FIBROSIS

• In cystic fibrosis, lung disease is typified by an inflammatory response. This leads to oxidative stress in the lungs. Glutathione is the primary intracellular antioxidant, and provides an important defense in the epithelial lining fluid. PMID: 10424526
• … GSH system dysfunction may be the trigger for initial depletion of other antioxidants and may also play a role in initiating the over-inflammation characteristic of cystic fibrosis. Proper GSH system functioning also affects immune system competence and mucus viscosity, both of relevance to cystic fibrosis pathophysiology. In a way, cystic fibrosis may be thought of as the first identified disease with GSH system dysfunction. PMID: 15658882
• Use of a daily GSH regimen appears to be associated in CF patients with significant improvement in lung function and weight, and a significant decline in bacteria cultured in this uncontrolled study. These findings bear further clinical investigation in larger, randomized, controlled studies. PMID: 18499536
• The results in this report revealed that GSH altered the sensitivity of Pseudomonas aeruginosa to different antibiotics through pathways unrelated to the oxidative stress as generally perceived. In addition, GSH and its oxidized form inhibited the growth of P. aeruginosa.PMID: 19557326

• Analyses of whole blood GSH showed that GSH was significantly lower in diabetic cases… PMID: 9586798
• An attractive hypothesis is that intracellular excesses of glucose inhibit the antioxidant systems primarily by its ability to cause depletion of the crucial protector GSH. The ultimate effects of such derangement of the protective systems against free radicals may involve vascular and neurological complications. (J Trace Elem Exp Med. 13:105-111. 2000)
• Oxidative stress has been proposed as a possible pathogenic factor for diabetic complications. It is relevant in determining cell replicative capacity and life span, and in vitro antioxidant treatment is able to reverse the impaired proliferative activity of different cell types. It was recently demonstrated that cultured skin fibroblasts from insulin-dependent diabetic patients with nephropathy age prematurely and have a shorter life cell cycle. GSH prevented the growth abnormalities of cells from DN (diabetic nephropathy) restoring it to values similar to that of the other two groups… The impaired growth of cultured fibroblasts from IDDM patients with nephropathy is prevented by GSH… PMID: 9621289
• Glutathione (GSH) is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation. Dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions. These include diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells. Manipulation of the GSH synthetic capacity is an important target in the treatment of many of these disorders. PMID: 18601945

• Decreased activity of key enzymes involved in GSH synthesis accompanied by a decreased availability of cyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency in IBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD. PMID: 9616308
• Finally, considering the results that others and we obtained by studies on GSH oral absorption in rat intestine, an oral therapy of GSH in Crohn's disease is suggested. PMID: 7710773
• The aim of this in vitro study was to evaluate the intracellular redox state and respiratory burst (RB) in neutrophils of patients with Crohn's disease (CD). This study demonstrated a decreased glutathione/glutathione disulfide (GSH/GSSG) ratio index of an increased oxidative state in CD patient neutrophils. PMID: 16446495
• Oxidative stress is an important factor in the pathogenesis of celiac disease. The antioxidant capacity of celiac patients is significantly reduced, mostly by a depletion of glutathione. Natural antioxidants and appropriate dietary supplements could be important complements to the classic therapy of celiac disease. PMID: 19560448
• The results obtained in this study demonstrate an enhanced inflammatory and oxidative stress and a decreased antioxidant status in patients with active Crohns disease. As the patients improved and became clinically stable, the oxidative parameters decreased, approaching normal values. PMID: 18253831
• The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients. PMID: 22441607

• Background and purpose: Glutathione (GSH) appears to have marked antioxidant activities and therefore may prevent cardiovascular disease (CVD)…. Conclusions: These findings suggest that reduced plasma tGSH levels are a risk factor for CVD, especially for cerebral small vessel disease. PMID: 15256685
• We present a mechanism based on animal studies, clinical data, and epidemiological data by which protein-energy status in the acute stroke and immediate post injury periods may affect outcome by regulating reduced glutathione (GSH), a key component of antioxidant defense. PMID: 12835106
• Blood samples from ten patients with clinically evident manifestations of atherosclerotic disease were used to evaluate in vitro the effects of exogenous glutathione (GSH) on platelet aggregation and on blood filtration and viscosity…. The venous GSH infusion both significantly decreased blood viscosity and increased blood filtration. Partial thromboplastin time was lengthened after GSH infusion even though it remained in the normal range. PMID: 1308476
• GSH levels were significantly decreased in AMI (Acute Myocardial Infarction) as compared to control (p<0.001). Also, total cholesterol and triglycerides were higher in AMI subjects (p<0.05). These finding suggest that depressed GSH levels may be associated with enhanced protective mechanism to oxidative stress in AMI. PMID: 12944689
• Oxygen free radicals have been shown to cause endothelial vasomotor dysfunction. This study examined the effect of reduced glutathione (GSH), an antioxidant, on human coronary circulation. The results indicate that GSH improved coronary endothelial vasomotor function, particularly in subjects with coronary risk factors, and it potentiated the vasodilator effect of nitroglycerin in human coronary arteries. PMID: 9639372
• OBJECTIVE: To assess the effects of glutathione on pain-free walking distance (PFWD) and hemodynamic parameters in patients with peripheral artery disease. CONCLUSION: In patients with peripheral artery disease, glutathione prolongs PFWD and shows an improvement of macrocirculatory and microcirculatory parameters. PMID: 12173710
• Glutathione redox state (E(h) GSH/GSSG), an in vivo measure of intracellular oxidative stress, is an independent predictor for the presence of early atherosclerosis in an otherwise healthy population. This finding supports a role for oxidative stress in the pathogenesis of premature atherosclerosis, and its measurement may help in the early identification of asymptomatic subjects at risk of atherosclerotic disease. PMID: 16516085

• Glutathione has been shown to be a significant factor in heavy metal mobilization and excretion, specifically with application to mercury, cadmium, and arsenic. Glutathione depletion and glutathione supplementation have specific effects on mercury toxicity, both by altering antioxidant status in the body and by directly affecting excretion of mercury and other heavy metals in the bile. PMID: 12495372
• Cells exposed to methylmercury showed a decrease in glutathione peroxidase activity. Simultaneous administration of 10 mM glutathione with 2.5 and 5.0 microM methylmercury dramatically prevented cell injury. PMID: 2315960
• All forms of mercury have toxic effects in a number of organs, especially in the kidneys. Because of the high bonding affinity between mercury and sulfur, there is particular interest in the interactions that occur between mercuric ions and the thiol group(s) of proteins, peptides and amino acids. Molecular interactions with sulfhydryl groups in molecules of albumin, metallothionein, glutathione, and cysteine have been implicated in mechanisms involved in the proximal tubular uptake, accumulation, transport, and toxicity of mercuric ions. PMID: 10699157
• Recent studies have shown that metals, including iron, copper, chromium, and vanadium undergo redox cycling, while cadmium, mercury, and nickel, as well as lead, deplete glutathione and protein-bound sulfhydryl groups, resulting in the production of reactive oxygen species as superoxide ion, hydrogen peroxide, and hydroxyl radical. As a consequence, enhanced lipid peroxidation. DNA damage, and altered calcium and sulfhydryl homeostasis occur. PMID: 7744317

• Oxidative stress may contribute to several aspects of HIV disease pathogenesis, including viral replication, inflammatory response, decreased immune cell proliferation, loss of immune function, apoptosis, chronic weight loss, and increased sensitivity to drug toxicities. Glutathione may play a role in these processes, and thus, agents that replete glutathione may offer a promising treatment for HIV-infected patients. PMID: 7590404
• Clinical studies presented here directly demonstrate that low GSH levels predict poor survival in otherwise indistinguishable HIV-infected subjects. Glutathione is essential for the viability and function of virtually all cells. In vitro studies showing that low GSH levels both promote HIV expression and impair T cell function suggesting a link between GSH depletion and HIV disease progression. …the unnecessary or excessive use of acetaminophen, alcohol, or other drugs known to deplete GSH should be avoided by HIV-infected individuals. PMID: 9050888
• Glutathione supplementation in vitro increases T cell proliferation and suppresses the spontaneous release of tumor necrosis factor–a from peripheral blood mononuclear cells, in HIV-infected patients receiving HAART (highly active antiretroviral therapy). Our findings suggest that therapeutic intervention aimed at normalization of oxidative disturbances in HIV infection could be of interest, in addition to HAART. PMID: 12854078
• Our data indicate that restoring both GSH concentration and mitochondrial function may hold promise as possible therapeutic strategies for slowing disease progression of dementia in AIDS patients. PMID: 11582518

• GSH has an anti-influenza activity in vitro and in vivo. Oxidative stress or other conditions that deplete GSH in the epithelium of the oral, nasal, and upper airway may, therefore, enhance susceptibility to influenza infection. PMID: 12654482
• Preparations possessing combined antioxidant/antihypoxic and detoxifying properties (reduced glutathione and hypoxene) produced a significant antiviral effect and enhanced the antiviral effect of rimantadine. (Also known as flumadine, an oral anti-viral drug used to treat Influenza A virus.) PMID: 18074805

• In patients with CHC, (chronic hepatitis C) particularly those who are HIV positive, a systemic depletion of GSH is present. This depletion may be a factor underlying the resistance to interferon therapy and, in patients who are HIV positive, to antiretroviral drugs, fostering HCV and/or HIV replication. PMID: 8946988
• We prospectively studied the effect of perioperative administration of glutathione on renal function in patients who underwent coronary artery bypass operation. Perioperative glutathione treatment has a salutary effect on perioperative renal function through effects on both renal hemodynamics and tubular mechanism. PMID: 7952483
• Regardless of the nature of the diet, cirrhotic patients had significantly subnormal values for cysteine, glutathione, and albumin. The data indicate multiple abnormalities in sulfur metabolism in cirrhosis. PMID: 6468868
• Although the use of non-heart-beating donors (NHBD) is the oldest type of organ transplantation, the results were and still are disappointing. To consider using a liver from NHBD, it is of importance to assess the graft viability. Our aim was to assess the role of reduced liver glutathione (rGSHL) as a potential predictive marker of liver function before transplantation. In conclusion, rGSHL has the potential of becoming an important viability marker, as it could predict survival in autotransplantation NHBD model regardless of the ischemia time. Further investigation to declare reasons for differing rGSHL levels within the liver is required. PMID: 18975272

• The prevalence of asthma has increased worldwide. The reasons for this rise remain unclear. Oxidative stress plays an important role in the pathogenesis of asthma. … results indicate that glutathione can modulate the early asthmatic reaction as well as the airway hyperresponsiveness. PMID: 20228417
• Glutathione is present in the epithelial lining fluid of the normal lower respiratory tract, where it is thought to play a major role in providing antioxidant protection to the epithelial cells. A study done on patients with IPF (idiopathic pulmonary fibrosis) showed the lower respiratory tracts to be chronically depleted of glutathione. PMID: 2913886
• We conclude that excessive oxidative stress and a lack of glutathione are associated with BOS after H/LTX (the most serious long-term sequel of lung or heart-lung transplantation ) and may play relevant roles in the development of this disorder. PMID: 10830222
• A study of asthmatic children found an inverse correlation between the level of glutathione and the severity of asthma attack. Lowest levels of glutathione were found during acute asthmatic attacks. PMID: 3189960
• Oxidant/antioxidant imbalance, a major cause of cell damage, is the hallmark for lung inflammation. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extra-cellular protective antioxidant against oxidative stress, which plays a key role in the control of signaling and pro-inflammatory processes in the lungs. PMID: 16054171
• Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro-inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. PMID: 11028671
• The mechanism of regulation of GSH in the epithelial lining fluid in the lungs of smokers and patients with COPD is not known. Knowledge of the mechanisms of GSH regulation in the lungs could lead to the development of novel therapies based on the pharmacological or genetic manipulation of the production of this important antioxidant in lung inflammation and injury. PMID: 10600876
• Modulation of intracellular glutathione (GSH) / thiol levels … demonstrated that both the stimulatory and the inhibitory effects of CSC (cigarette smoke condensate) were regulated in part by intracellular GSH levels. PMID: 16309548

• (Regarding the mold aflatoxin)… GSH plays a protective role in AFB1-induced cell damage… PMID: 15971552
• Reduced glutathione administered to rats bearing aflatoxin B1-induced liver tumors caused regression of tumor growth and resulted in survival of the animals. Since glutathione is a harmless natural product, it merits further investigation as a potential antitumor drug for humans. PMID: 6782675
• …a representative antioxidant glutathione significantly alleviated this oxidative mitochondrial damage induced by butenolide (A mycotoxin formed by the mold fusarium)… PMID: 19778250
• A review of the diagnosis and treatment of Ochratoxin A inhalational exposure associated with human illness and kidney disease including focal segmental glomerulosclerosis. PMID: 22253638 | Article on hindawi.com

• Colorectal cancer is associated with oxidative stress, and assessment of oxidative stress and given antioxidants is important for the treatment and prevention of colorectal cancer. PMID: 18837290
• The significant changes in antioxidant enzyme activity after GSH depletion suggest that thiol status can influence the regulation of other antioxidant enzymes. PMID: 15947071
• In conclusion, our findings show that the glutathione redox system is affected by age. Oxidative stress increases during the aging process. PMID: 11835271
• These findings confirm that high blood (glutathione) concentrations and excellent physical and mental health are characteristics of long-lived women. PMID: 12486409
• These results provide evidence that increased oxidative stress with aging makes chondrocytes more susceptible to oxidant-mediated cell death through the dysregulation of the glutathione antioxidant system. This may represent an important contributing factor to the development of osteoarthritis in older adults. PMID: 14673993
• A deficiency in GSH puts the cell at risk for oxidative damage. An imbalance in GSH is observed in a wide range of pathologies, such as cancer, neurodegenerative diseases, cystic fibrosis (CF), several viral infections including HIV-1, as well as in aging. PMID: 18926849
• The reducing compound glutathione (GSH) exists in an unusually high concentration in the lens where it functions as an essential antioxidant vital for maintenance of the tissue's transparency. PMID: 10803423

• Glutathione is an important intracellular antioxidant that protects against a variety of different antioxidant species. An important role for glutathione was proposed for the pathogenesis of Parkinson's disease, because a decrease in total glutathione concentrations in the substantia nigra has been observed in preclinical stages, at a time at which other biochemical changes are not yet detectable. PMID: 10931172
• Levels of reduced glutathione are decreased in nigra in Parkinson's disease… These data suggest that changes in glutathione function are an early component of the pathological process of Parkinson's disease. PMID: 1510385
• Rational, integrative management of Parkinson's disease requires, among other things, aggressive repletion of glutathione. PMID: 11134975
• Past studies have shown that depletion of the naturally occurring antioxidant in the affected area of the brain is one of the earliest signs of PD, but this study shows that glutathione depletion may be a causal factor in the disorder. PMID: 18094238
• Because of the scavenging activity of glutathione against accumulation of oxygen radicals, its decrease in the brains of Parkinsonion patients has been interpreted as a sign of oxidative stress; however, this change may also result from or lead to mitochondrial damage. It is conceivable therefore that regardless of whether oxidative stress or mitochondrial damage represents the initial insult, these toxic mechanisms may both contribute to neuronal degeneration via changes in glutathione levels. PMID: 1510368
• Several studies have demonstrated a deficiency in reduced glutathione (GSH) in the nigra of patients with Parkinson's Disease (PD). In particular, the magnitude of reduction in GSH seems to parallel the severity of the disease. GSH was administered intravenous, 600 mg twice daily, for 30 days… All patients improved significantly after GSH therapy, with a 42% decline in disability. PMID: 8938817

• Rhinoviruses are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. Rhinovirus infection induced intracellular depletion of reduced glutathione (GSH)…Increasing intracellular GSH with exogenous H2S or GSH prevented both rhinovirus-mediated intracellular GSH depletion and rhinovirus-induced superoxide production. PMID: 18678861