MaxGXL and Glutathione

The following excerpts are taken from the Internet. Google “Glutathione” and the search will produce about 7,970,000 Glutathione related listings. The following items are about Glutathione related articles concerning diabetes, the immune system, aging, cancer, cardiovascular disease, sleep loss, Parkinson's disease, Chronic Fatigue Syndrome, Atherosclerosis, Alzheimer's disease, and other disorders and illnesses.

Evidence for Accelerated Rates of Glutathione Utilization and Glutathione Depletion in Adolescents with Poorly Controlled Type 1 Diabetes

Dominique Darmaun, Shiela D. Smith, Shawn Sweeten, Brenda K. Sager, Susan Welch, and Nelly Mauras 1

Endocrine Research Department, Nemours Children’s Clinic, Jacksonville, Florida
Human Nutrition Research Center, Institut National de la Santé et de la Recherche Médicale (INSERM) U.539, Nantes, France

Depletion of glutathione, an important antioxidant present in red cells, has been reported in type 1 diabetes, but the mechanism of this depletion has not been fully characterized. Glutathione depletion can occur through decreased synthesis, increased utilization, or a combination of both. To address this issue, 5-h infusions of L-[3,3- 2H 2]cysteine were performed in 16 diabetic adolescents divided into a well-controlled and a poorly controlled group and in eight healthy nondiabetic teenagers as control subjects (HbA 1c 6.3 ± 0.2, 10.5 ± 0.6, and 4.8 ± 0.1%, respectively). Glutathione fractional synthesis rate was determined from H 2-cysteine incorporation into blood glutathione. We observed that 1) erythrocyte cysteine concentration was 41% lower in poorly controlled patients compared with well-controlled patients (P = 0.009); 2) erythrocyte glutathione concentration was 29% and 36% lower in well-controlled and poorly controlled patients compared with healthy volunteers; and 3) the fractional synthesis rate of glutathione, although similar in well-controlled and healthy subjects (83 ± 14 vs. 82 ± 11% per day), was substantially higher in the poorly controlled group (141 ± 23% per day, P = 0.038). These findings suggest that in diabetic adolescents, poor control is associated with a significant depletion of blood glutathione and cysteine, due to increased rates of glutathione utilization. This weakened antioxidant defense may play a role in the pathogenesis of diabetes complications.

Address correspondence to Dominique Darmaun, MD, PhD, Nemours Children’s Clinic, Research Department, 5 North, 807 Children’s Way, Jacksonville, FL 32207.

From “The Natural Healer” magazine article by Josué Cinéus

Glutathione has three important functions: It serves as an Antioxidant, an Immune system enhancer and a Detoxifier. It has been dubbed the essential health AID.

As an antioxidant, glutathione (often abbreviated as GSH) is the most powerful antioxidant that protects against free radical damages or “oxidative stresses,” which have been implicated in a number of illnesses such as heart disease, cancer, diabetes and even the negative effects of aging.As an immune system enhancer, glutathione is needed for the proper functioning, and in particular the creation and maintenance, of T-cells lymphocytes, the body’s front-line defense against infection.As a detoxifier, dozens of toxins are eliminated by the glutathione enzyme system, including heavy metals, cigarette smoke, fuel exhaust and other carcinogens.

The Role of Glutathione in Aging and Cancer

American Health Foundation, Valhalla, New York 10595.

The incidence and mortality rates from most cancers increase exponentially with age. It is likely that this aging phenomenon is partially due to specific changes that occur in the host resulting in an increased susceptibility to neoplasia. Our hypothesis is that one such host factor is a deficiency in GSH, based on the importance of this compound in the detoxification of a wide variety of exogenous and endogenous carcinogens and free radicals, as well as in the maintenance of immune function.

Glutathione in Trauma Patients

Imo P Aisiku, I Marc Moss and George Cotsonis

Virgina Commonwealth University/Medical College of Virginia (VCU/MCV): Richmond, VA, Emory University: Atlanta, GA

Glutathione has been implicated in the pathogenesis of various disease states including sickle cell anemia, acute lung injury, and chronic alcoholism. Trauma patients are usually young and otherwise healthy. Severely injured trauma patients are at an increased risk of sepsis and acute lung injury. Acute alterations in serum glutathione in trauma patients have not previously been reported. Serum glutathione concentrations are decreased acutely in severely injured trauma patients.

Relationship Between Plasma Glutathione Levels and Cardiovascular Disease in a Defined Population

Haruki Shimizu, MD; Yutaka Kiyohara, MD; Isao Kato, MD; Takanari Kitazono, MD; Yumihiro Tanizaki, MD; Michiaki Kubo, MD; Hirofumi Ueno; Setsuro Ibayashi, MD; Masatoshi Fujishima, MD Mitsuo Iida, MD

From the Department of Medicine and Clinical Science (H.S., Y.K., I.K., T.K., Y.T., M.K., S.I., M.F., M.I.), Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan; and the Saga Research Institute of Ohtsuka Pharmaceutical Co, Ltd (H.U.), Saga, Japan.

Correspondence to Dr Haruki Shimizu, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka City, 812-8582 Japan

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 GSH levels are a risk factor for CVD, especially for cerebral small vessel disease.

Glutathione Intervention in Diabetes Mellitus

Theresa Chen with Walter Williams

University of Louisville

Atherosclerosis (AS) is the leading cause of death in patients with diabetes mellitus (DM). Several lines of evidence suggest that oxidative stress is involved in the development of DM and AS. A possible correction is to intervene by altering glutathione (GSH) status, the most abundant cellular antioxidant. This is based on a combined GSH and cysteine (Cys) deficiency occurs in DM. Our hypothesis is that GSH-Cys status plays an important role in the pathophysiology of DM and its related condition, obesity. The expected results should lead to new insights into an old problem and provide a potential treatment for diabetes and its cardiovascular complications.

Glutathione levels in patients with Erectile Dysfunction, with or without diabetes mellitus

Dipartimento di Medicina Interna, Azienda Sanitaria Ospedaliera S. Giovanni Battista, C.so Dogliotti, 14, I-10126 Torino, Italy.

The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essential cofactor for nitric oxide (NO) synthase that synthesizes NO from l-arginine. Reduced levels of GSH, due both to a hyperglycaemia-induced increase of free radical production and to a decrease of NADPH levels [like in diabetes mellitus (DM)], can hamper the endothelial cell functions. This condition may play an important role in the aetiology of some clinical signs, like erectile dysfunction (ED). The aim of this study was to test the hypothesis that GSH concentration is reduced in patients with ED and type 2 diabetes mellitus. We studied 111 male patients with ED: 64 with diabetes (ED/DM) and 47 without diabetes (ED/wDM); 20 patients with diabetes but without ED (DM) and 26 male normal subjects as a control group (C). The GSH red blood cell concentration was significantly lower in ED than in C (X ± SD; 1782.12 ± 518.02 vs. 2269.20 ± 231.56 μmol/L, p < 0.001). In particular, GSH was significantly reduced in ED/DM vs. ED/wDM (1670.74 ± 437.68 vs. 1930.63 ± 581.01 μmol/L, p < 0.01). In DM, GSH was significantly lower than in C and significantly higher than in ED/DM (2084.20 ± 118.14 vs. 2269.20 ± 231.56 and vs. 1670.74 ± 437.68 μmol/L, p < 0.002 and p < 0.001 respectively). GSH showed a negative correlation with fasting glucose concentrations (r = −0.34, p < 0.01) and with the duration of DM (r = −0.25, p < 0.05). A GSH depletion can lead to a reduction of NO synthesis, thus impairing vasodilation in the corpora cavernosa.

Antioxidant defense responses to Sleep Loss and Sleep Recovery

Carol A. Everson, Christa D. Laatsch, and Neil Hogg

Departments of Neurology and Biophysics and Free Radical Research Center, The Medical College of Wisconsin, Milwaukee, Wisconsin

Accepted in final form 30 September 2004.

Sleep deprivation in humans is widely believed to impair health, and sleep is thought to have powerful restorative properties . The specific physical and biochemical factors and processes mediating these outcomes, however, are poorly elucidated. Sleep deprivation in the animal model produces a condition that eventually becomes highly lethal, lacks specific localization, and is reversible with sleep, implying mediation by a biochemical abnormality. Metabolic and immunological consequences of sleep deprivation point to a high potential for antioxidant imbalance. The objective, therefore, was to study glutathione content in the liver, heart, and lung, because glutathione is considered a major free radical scavenger that reflects the degree to which a tissue has been oxidatively challenged. We also investigated major enzymatic antioxidants, including catalase and glutathione peroxidase, as well as indexes of glutathione recycling. Catalase activity and glutathione content, which normally are tightly regulated, were both decreased in liver by 23–36% by 5 and 10 days of sleep deprivation. Such levels are associated with impaired health in other animal models of oxidative stress-associated disease. The decreases were accompanied by markers of generalized cell injury and absence of responses by the other enzymatic antioxidants under study. Enzymatic activities in the heart indicated an increased rate of oxidative pentose phosphate pathway activity during sleep deprivation. Recovery sleep normalized antioxidant content in liver and enhanced enzymatic antioxidant activities in both the liver and the heart. The present results link uncompensated oxidative stress to health effects induced by sleep deprivation and provide evidence that restoration of antioxidant balance is a property of recovery sleep.

Decreases in brain Glutathione levels induced by Sleep Deprivation

Department of Psychobiology, Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Sao Paulo, Brazil.

Recent findings from this laboratory revealed that sleep deprivation reduces total glutathione (GSH) levels in hypothalamus, suggesting an increased vulnerability to oxidative damage. These results confirm that sleep deprivation reduces hypothalamic GSH…

Parkinson’s disease : A Disorder due to Nigral Glutathione deficiency…

National Library of Medicine and the National Institutes of Health

Perry, Godin, Hansen

Amino acid analysis of autopsied human brain showed reduced glutathione (GSH) content significantly lower in the substantia nigra than in other brain regions. GSH was virtually absent in the nigra of patients with Parkinson's disease. Oxidative degradation of L-DOPA and dopamine in vivo may generate reactive oxygen species (hydrogen peroxide, superoxide, hydroxyl radical, or singlet oxygen) which can damage membranes and other cellular components. Since GSH is an important natural antioxidant, a deficiency of GSH in the substantia nigra could make this region vulnerable to oxidative injury. If confirmed, the hypothesis that loss of nigrostriatal dopaminergic neurons results from a regional GSH deficiency could have important therapeutic implications for the management and prevention of Parkinson's disease.

Chronic fatigue syndrome

Department of Surgery, McGill University, and Medical Research Council of Canada.

The chronic fatigue syndrome (CFS) is typically associated or follows a recognized or presumed infection. Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen. As an antioxidant, glutathione (GSH) is essential for allowing the lymphocyte to express its full potential without being hampered by oxiradical accumulation. Hence, protracted challenge of the immunocytes may lead to cellular GSH depletion. Because GSH is also essential to aerobic muscular contraction, an undesirable competition for GSH precursors between the immune and muscular systems may develop. 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.

Mitochondrial and GSH in Neurodegeneration and Lewdy Body diseases

University Department of Clinical Neurosciences, Royal Free Hospital School of Medicine, London, UK.

…Oxidative stress and complex I deficiency have both been identified in the substantia nigra in Parkinson's disease but their place in the sequence of events resulting in dopaminergic cell death is uncertain. We have analysed respiratory chain activity, iron and reduced glutathione concentrations in Parkinson's disease substantia innominata and in the cingulate cortex of patients with Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies to investigate their association with neuronal death and Lewy body formation. No abnormalities of mitochondrial function, iron or reduced glutathione levels were identified in Parkinson's disease substantia innominata or cingulate cortex. Mitochondrial function also appeared to be unchanged in cingulate cortex from patients with Alzheimer's disease and from patients with dementia with Lewy bodies, however, iron concentrations were mildly increased in both, and reduced glutathione decreased only in Alzheimer's disease. These results confirm the anatomic specificity of the complex I deficiency and decreased levels of reduced glutathione within the Parkinson's disease brain and suggest that these parameters are not associated with cholinergic cell loss in Parkinson's disease nor with Lewy body formation in this or other diseases. We propose that our data support a 'two-hit' hypothesis for the cause of neuronal death in Parkinson's disease.

Max International Independent Associate