This section contains links to the abstracts of published research regarding glutathione and its relationship to various disease conditions. Information about the research can be found on the U.S. National Institutes of Health (NIH) digital archive of biomedical journals, www.pubmed.gov.
Use the scroll bar on the right to find the condition that interests you. The presentation of glutathione used in these studies may vary, but these articles will give you an idea of the wide application range and stunning importance of glutathione.
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
GSH was statistically decreased in alcohol abusers… PMID: 17977706
Specifically, chronic alcohol ingestion decreases the levels of the antioxidant glutathione within the alveolar space by as much as 80-90%, and, as a consequence, impairs alveolar epithelial surfactant production and barrier integrity, decreases alveolar macrophage function, and renders the lung susceptible to oxidant-mediated injury. PMID: 17220370
Depletion of mitochondrial GSH by alcohol is believed to contribute to the sensitization of the liver to alcohol-induced injury through tumor necrosis factor (TNF)-mediated hepatocellular death. Through control of mitochondrial electron transport chain-generated oxidants, mitochondrial GSH modulates cell death and hence its regulation may be a key target to influence disease progression and drug-induced cell death. PMID: 15845418
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
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
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
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
… 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
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
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
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
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
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
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
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
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
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
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
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