Glutathione protective effects

Jaeschke, H. (1990). Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo-, the protective effect of allopurinol. J. Pharmacol Exp. Ther. 255, 935-941. 

Mutoh, H., Hiraishi, H., Ota, S., Yoshida, H., Ivey, K.J., Terano, A. and Sugimoto, T. (1990b). Protective effect of intracellular glutathione a nst ethanol-induced damage in cultured rat tric mucosal cells. Gastroenterology 98, 1452-1459. 

Smith RP, Abbant RA. 1966. Protective effect of oxidized glutathione in acute sulfide poisoning. Toxicol Appl Pharmacol 9 209-217. 

Numan IT, Hassan MQ, Stohs SJ. 1990b. Protective effects of antioxidants against endrin-induced lipid peroxidation, glutathione depletion, and lethality in rats. Arch Environ Contam Toxicol 19 302-306. 

All aerobic organisms contain substances that help prevent injury mediated by free radicals, and these include antioxidants such as a-tocopherol and the enzymes superoxide dismutase and glutathione peroxidase. When the protective effect of the antioxidants is overwhelmed by the production of reactive oxygen species, the intracellular milieu becomes oxidative, leading to a state known as oxidative stress (Halliwell and Gutteridge, 1999). Thus the balance between the generated free radicals and the efficiency of the protective antioxidant system determines the extent of cellular damage. 

Mahfoud, R. et al., The mycotoxin patulin alters the barrier function of the intestinal epithelium mechanism of action of the toxin and protective effects of glutathione, Toxicol. Appl. Pharmacol., 181, 209, 2002. 

The diterpenes andrographolide, andrographiside and neoandro-grapholide isolated from A. paniculata were also investigated for their protective effects on hepatotoxicity induced in mice by carbon tetrachloride or /ert-butylhydroperoxide ( BHP) intoxication by Kapil et pretreatment of mice with the individual diterpenes at a dose of 100 mg/kg, i.p. for 3 consecutive days were observed to produce significant reduction in malondialdehyde formation, reduced glutathione (GSH) depletion and... 

Inhalation exposure of male B6C3Fi mice to dichloromethane (6 h, once) led to vacuolation of bronchiolar cells at exposure levels > 2000 ppm [6940 mg/m ], while no effect was obsened at levels < 1000 ppm [3470 mg/m (Foster et al., 1994). Pretreatment with the cytochrome P450 inhibitor piperonyl butoxide (300 mg/kg intraperi-toneally) 1 h before the exposure practically abolished the toxic effect upon bronchiolar cells, while buthionine sulfoximine (1 g/kg intraperitoneally), which decreased the pulmonary glutathione content by 50%, had no such protective effect. In Clara cells isolated after exposure to dichloromethane exposure (> 1000 ppm), the proportion of cells in tlie S-phase was increased. 

Gao, P., Thornton-Manning, J.R. Pegram, R.A. (1996) Protective effects of glutathione on bromodichloromethane in vivo toxicity and in vitro macromolecular binding in Fischer 344 rats. J. Toxicol, environ. Health, 49, 145-159... 

Zang et al [140] reported the liver protective effects of the saponins isolated from A. membranaceus and A. sieversianus against chemical injury induced by CCU, D-galactosamine and acetaminophen in mice. In all cases there were positive activities and the saponins inhibited the rise in SGPT levels, decreased the malondialdehyde (MDA) content and increased the glutathione reduced (GSH) concentration in mouse liver. The same compounds were also evaluated in cultured rat hepatocytes, and the results indicated that the activity may be due to to the antioxidative activity of the saponins, since the content of liver protein in treated mice was more than the control. Moreover, in all treated mice, the level of hepatic microsomal cytochrome P-450 was increased. The liver metabolism and immunoregulating action produced by saponins may be also involved in their hepato-protective effects. Similar results were obtained by Zhang et al [141] when they studied the activity in vitro and... 

Fig. (3). Mechanisms implicated in the protective effect of flavonoids in LDL oxidation. OX-LDL oxidized LDL CE cholesteryl ester UC unesterified cholesterol GSH glutathione SOD superoxide dismutase ROS radical oxygen species. Dashed lines represent inhibition.

Saija A., Princi P., Pisani A., Lanza M., Scalese M., Aramnejad E., Ceserani R., and Costa G. (1994). Protective effect of glutathione on kainic acid-induced neuropathological changes in the rat brain. Gen. Pharmacol. 25 97-102. 

In rats, hepatic ischaemia is associated with reduced ATP levels but normal lipid peroxide formation. Reperfusion gives a slow recovery of ATP levels, a reduction in endogenous vitamin E and glutathione, but an increase in lipid peroxidation. Vitamin-E-treated animals showed accelerated ATP synthesis with a suppression of the increased lipid peroxidation [ 170, l7l]. Ischaemia of liver tissue reduced the metabolism of xenobiotics. Vitamin E was protectant against this effect [172]. The protective effect is related to an increase in catalytic activity of cytochrome P-450, to antioxidant and membrane-stabilizing properties [173]. In kidney tissue, prophylactic injection of vitamin E and synthetic antioxidants prevented the development of lesions during acute renal ischaemia and subsequent reperfusion. These effects were related therefore to the vitamin s antioxidant ability. 

T6. Tsakiris, S., Angelogianni, P, Schulpis, K. H., and Behrakis, P., Protective effect of L-cysteine and glutathione on rat brain Na+,K+-ATPase inhibition induced by free radicals. Z. Naturforsch. 55c, 271-277 (2000). 

The activity of sulfur towards platinum complexes has led to investigation of so-called rescue agents to ameliorate the side effects of platinum therapy, without compromising its anti-tumor activity. These nucleophilic sulfur compounds include sodium thiosulfate (STS), sodium diethyldithio-carbamate (Naddtc), (S)- 2-[(3-aminopropyl)amino]ethyl phosphorothioic acid (WR-2721, Ethyol , amifostine), glutathione (GSH), methionine, thiourea, cysteine, -acetylcysteine, penicillamine, biotin, sulfathiazole, sodium 2-mercaptoethanesulfonate (mesna), and its dimer (di)mesna (BNP-7787). The protective effect of these compounds is either due to prevention, or reversal of Pt-S adducts in proteins. Some of the more promising of the above-mentioned compounds (see Fig. 1) will be discussed below. 

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