CHRYSOTILE INHIBITS GLUTATHIONE-DEPENDENT PROTECTION AGAINST THE ONSET OF LIPID-PEROXIDATION IN RAT LUNG MICROSOMES

The glutathione and vitamin E-dependent protection of lipid peroxidati on in an NADPH (0.4 mM) and chrysotile (500 mu g/ml) containing system were investigated in vitro in rat lung microsomes. Addition of 1 mM g lutathione to the above reaction system containing microsomes suppleme nted with vitamin E (1 nmol/mg protein) reduced lipid peroxidation. Si milar protection by glutathione could be observed in normal unsuppleme nted microsomes though the degree of protection was less pronounced. A ddition of free radical scavengers such as, superoxide dismutase (100 units/ml), catalase (150 units/ml), mannitol (1 mM) and D-carotene (0. 5 mM) to the reaction system showed an insignificant effect on lipid p eroxidation. When the reaction was carried out in absence of glutathio ne, vitamin E content of peroxidizing microsomes decreased rapidly. In this system a concomitant increase in the activity of microsomal glut athione-S-transferase was observed which may serve as an alternative p athway to detoxify lipid peroxides. Addition of glutathione alone to t he reaction system prevented both against the loss in vitamin E conten t and increase in the activity of glutathione-S-transferase. Supplemen tation of both vitamin E and glutathione was found to be effective in lowering glutathione-S-transferase activity to that of normal basal le vel. Our results suggest that chrysotile-mediated stimulation of NADPH -dependent lipid peroxidation may be due to hampering of glutathione-d ependent protection which may ultimately exhaust membrane bound vitami n E. Our data further suggest that the lung tissue may have an inbuilt mechanism whereby glutathione-S-transferase may be triggered to cope with the excessive production of lipid peroxides.