Glutathione lipid peroxidation

Coban, T., Y. Beduk, and M. Iscan. 1996. In vitro effects of cadmium and nickel on glutathione, lipid peroxidation and glutathione 5-transferase in human kidney. Toxicol, in Vitro 10 241-245. 

In the previous section, we have described some of the mechanisms that may lead to the fijrmation of lipid hydroperoxides or peroxyl radicals in lipids. If the peroxyl radical is formed, then this will lead to propagation if no chain-breaking antioxidants are present (Scheme 2.1). However, in many biological situations chain-breaking antioxidants are present, for example, in LDL, and these will terminate the peroxyl radical and are consumed in the process. This will concomitandy increase the size of the peroxide pool in the membrane or lipoprotein. Such peroxides may be metabolized by the glutathione peroxidases in a cellular environment but are probably more stable in the plasma comjxutment. In the next section, the promotion of lipid peroxidation if the lipid peroxides encounter a transition metal will be considered. 

Comporti, M. (1987). Glutathione depleting agents and lipid peroxidation. Chem. Phys. Lipids 45, 143-169. 

Furthermore, depletion of hepatic GSH induced chemically or by fasting augmented hepatic I/R-induced enzyme release and promoted lipid peroxidation (Jennische, 1984 Stein et al., 1991) Benoit et al. (1992) have used portacaval-shunted rats as a model of chronic hepatic ischaemia, and were able to show decreases in total levels of SOD and xanthine dehydrogenase, but no significant change in catalase or glutathione peroxidase. 

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. 

Shaw, S., Rubin, K.P. and Lieber, C.S. (1983). Depressed hepatic glutathione and increased diene conjugates in alcoholic liver disease evidence of lipid peroxidation. Dig. Dis. Sci. 28, 585-589. 

Stohs, S.J., Hassan, M.Q. and Murray, W.J. (1984). Effects of a-tocopherol and retinol acetate on TCDD-mediated changes in lipid peroxidation, glutathione peroxidase activity and survival. Xenobiotica 14, 533-537. 

Normally, the cascade from oxygen to water is well controlled by SOD, catalase and endogenous antioxidants such as glutathione, ascorbate and vitamin E. Vitamin E is the most important membrane-bound antioxidant. However, during ischaemia, the local control of ROS is lost, thus reactive free radicals can attack the membranes and lipid peroxidation begins. Endogenous antioxidants can be supplemented. This section describes this supplementation strategy. 

Thiols are also important protection against lipid peroxidation. Glutathione (7-Glu-Cys-Gly) is used by several glutathione-dependent enzymes such as free-radical reductase (converts vitamin E radical to vitamin E), glutathione peroxidase (reduces hydrogen peroxide and lipid hydroperoxides to water and to the lipid alcohol, respectively), and others. In addition, the thiol group of many proteins is essential for function. Oxidation of the thiol of calcium ATPases impairs function and leads to increased intracellular calcium. Thiol derivatives such as the ovothiols (l-methyl-4-mercaptohistidines) (Shapiro, 1991) have been explored as therapeutics. 

Ebselen is a seleno-oiganic that mimics glutathione peroxidase and inhibits iron-stimulated lipid peroxidation. It significandy reduced both inferct size and oedema progression in the middle cerebral artery exclusion (MCAO) focal model of stroke in tats (Matsui et al. 1990). Ebselen has also been shown to be an effective anti-inflammatory agent in a H202-dependent inflammation model in tats (Parnham 1991). 

Other examples of possible damaging effects of radio frequency MFs on humans are the MF effects on cellular phones. Moustafa et al. [216] suggested that acute exposure to the MFs of commercially available cellular phones for 1, 2, or 4 h significantly increased plasma lipid peroxidation and decreased the activities of SOD and glutathione peroxidase in erythrocytes. 

As a rule, oxygen radical overproduction in mitochondria is accompanied by peroxidation of mitochondrial lipids, glutathione depletion, and an increase in other parameters of oxidative stress. Thus, the enhancement of superoxide production in bovine heart submitochondrial particles by antimycin resulted in a decrease in the activity of cytochrome c oxidase through the peroxidation of cardiolipin [45]. Iron overload also induced lipid peroxidation and a decrease in mitochondrial membrane potential in rat liver mitochondria [46]. Sensi et al. [47] demonstrated that zinc influx induced mitochondrial superoxide production in postsynaptic neurons. 

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