Glutathione levels

RiMBACH G, VIRGILI F, PARK Y c and PACKER L (1999) Effect of procyanidins fromPinus maritima on glutathione levels in endothelial cells challenged by 3-morpholinosyndonimine or activated macrophages Redox Report 4, 171-7. 

The Na/K ATPase has been extensively purified and characterized, and consists of a catalytic a subunit of around 95 kDa and a glycoprotein 0 subunit of approximately 45 kDa (Skou, 1992). The functional transporter exists as a dimer with each monomer consisting of an a and /3 subunit. Hiatt aal. (1984) have su ested that the non-catalytic jS subunit may be involved in the cottect insertion of the a subunit into the lipid bilayer and, therefore, it is conceivable that a modification of the 0 subunit structure may be reflected by changes in the catalytic activity of the a subunit. Therefore, in studies involving the manipulation of tissue glutathione levels, alterations of intracellular redox state may have an effect on substrate binding at an extracellular site on this ion-translocating protein. 

Whilst experimentally it is relatively easy to investigate the eflFect of the exogenous application of GSH and GSSG on cardiac Na/K ATPase activity, one further approach that has been exploited in many aspects of oxidant-induced cell injury has been the depletion of cellular glutathione levels. The hypothesized importance of GSH in the cell s antioxidant armoury would be expected to be reflected in an increased susceptibility to oxidant stress-... 

Sai, K., Takagi, A., Umemura, T., Hasegawa, R. and Kurokawa, T. (1991). Relation of 8-hydroxydeoxyguanosine formation in rat kidney to lipid peroxidation, glutathione level and relative organ weight after a single administration of potassium bromate. Jpn. J. Cancer Res. 82, 165-169. 

Tsukamoto N, Chen J, Yoshida A. Enhanced expressions of glucose-6-phos-phate dehydrogenase and cytosolic aldehyde dehydrogenase and elevation of reduced glutathione level in cyclophosphamide-resistant human leukemia cells. Blood Cells Mol Dis 1998 24 231-238. 

Some effects in the liver have been reported, but they may be adaptive changes related to increased metabolic activity. Increased glutathione levels were reported at doses of 70 mg/kg/day for 21 days (Szabo et al. 1977). Because the metabolism of acrylonitrile includes pathways that utilize glutathione (see Section 2.3.3), the higher glutathione levels in the liver may be due to increased demand for glutathione for the metabolism of acrylonitrile. 

Chen MF, Chen LiT and Boyce HW, Jr. 1995. Cruciferous vegetables and glutathione their effects on colon mucosal glutathione level and colon tumor development in rats induced by DMH. Nutr Cancer 23(1) 77—83. 

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

Sanders et al. [133] found that although quercetin treatment of streptozotocin diabetic rats diminished oxidized glutathione in brain and hepatic glutathione peroxidase activity, this flavonoid enhanced hepatic lipid peroxidation, decreased hepatic glutathione level, and increased renal and cardiac glutathione peroxidase activity. In authors opinion the partial prooxidant effect of quercetin questions the efficacy of quercetin therapy in diabetic patients. (Antioxidant and prooxidant activities of flavonoids are discussed in Chapter 29.) Administration of endothelin antagonist J-104132 to streptozotocin-induced diabetic rats inhibited the enhanced endothelin-1-stimulated superoxide production [134]. Interleukin-10 preserved endothelium-dependent vasorelaxation in streptozotocin-induced diabetic mice probably by reducing superoxide production by xanthine oxidase [135]. 

At present, antioxidants are extensively studied as supplements for the treatment diabetic patients. Several clinical trials have been carried out with vitamin E. In 1991, Ceriello et al. [136] showed that supplementation of vitamin E to insulin-requiring diabetic patients reduced protein glycosylation without changing plasma glucose, probably due to the inhibition of the Maillard reaction. Then, Paolisso et al. [137] found that vitamin E decreased glucose level and improved insulin action in noninsulin-dependent diabetic patients. Recently, Jain et al. [138] showed that vitamin E supplementation increased glutathione level and diminished lipid peroxidation and HbAi level in erythrocytes of type 1 diabetic children. Similarly, Skyrme-Jones et al. [139] demonstrated that vitamin E supplementation improved endothelial vasodilator function in type 1 diabetic children supposedly due to the suppression of LDL oxidation. Devaraj et al. [140] used the urinary F2-isoprostane test for the estimate of LDL oxidation in type 2 diabetics. They also found that LDL oxidation decreased after vitamin E supplementation to patients. 

Overproduction of free radicals by erythrocytes and leukocytes and iron overload result in a sharp increase in free radical damage in T1 patients. Thus, Livrea et al. [385] found a twofold increase in the levels of conjugated dienes, MDA, and protein carbonyls with respect to control in serum from 42 (3-thalassemic patients. Simultaneously, there was a decrease in the content of antioxidant vitamins C (44%) and E (42%). It was suggested that the iron-induced liver damage in thalassemia may play a major role in the depletion of antioxidant vitamins. Plasma thiobarbituric acid-reactive substances (TBARS) and conjugated dienes were elevated in (3-thalassemic children compared to controls together with compensatory increase in SOD activity [386]. The development of lipid peroxidation in thalassemic erythrocytes probably depends on a decrease in reduced glutathione level and decreased catalase activity [387]. 

Vogiatzis, A.K. and N.S. Loumbourdis. 1998. Cadmium accumulation in liver and kidneys and hepatic metallothionein and glutathione levels in Rana ridibunda, after exposure to CdCl2. Arch. Environ. Contam. Toxicol. 34 64-68. 

Peterson, J.D. et al., Glutathione levels in antigen-presenting cells modulate Thl versus Th2 response patterns, I roc. Natl. Acad. Sci. U. S. A, 95, 3071, 1998. 

Gruetter, C. A., Lemke, S. M., Dissociation of cysteine and glutathione levels from nitroglycerin-induced relaxation. 

Seif-EI-Nasr M, El-Fattah AA. (1995). Lipid peroxide, phospholipids, glutathione levels and superoxide dismutase activity in rat brain after ischaemia effect of Ginkgo biloba extract. Pharmacol Res. 32(5) 273-78. 

Studies on the mechanism of thiourea toxicity have shown that thioureas have a high degree of specificity for pulmonary endothelial cells and that thioureas require metabolic activation before toxic effects are manifested. Reduced glutathione levels have been associated with increased toxicity, but there is no evidence to suggest that the appearance of edema coincides with a decrease in glutathione. Furthermore, the induction of tolerance or resistance is not correlated with an increase in glutathione levels in rats. ... 

Cresols are formed from the commonly found amino acid tyrosine, and occur naturally in human and animal tissues, fluids, and urine. Cresols are also formed as minor metabolites of toluene, and an increased presence of cresol in the body could be due to exposure to this substance. Therefore, even the cresols themselves cannot be considered to be biomarkers of cresol exposure unless very high levels are found. There is some evidence that methemoglobinemia, reduced glutathione levels in red blood cells, and Heinz body formation are associated with oral exposure to cresols in humans (Chan et al. 1971 Cote et al. 1984), but these effects are too general and occur at too high doses to be useful as biomarkers of exposure to cresols. 

Abdel-Rahman and coworkers (Abdel-Rahman et al. 1984b Couri and Abdel-Rahman 1980) also exposed male rats to sodium chlorite in the drinking water, 20 hours/day for up to 1 year, at concentrations that resulted in estimated doses of 1 or 10 mg/kg/day. Both dose levels resulted in increased mean corpuscular hemoglobin concentration (after 7, but not 9 months) and decreased osmotic fragility after 7-9 months). Erythrocyte glutathione levels were significantly decreased at dose levels 0.1 mg/kg/day by the end of the... 

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