PREVENTION OF CARBON TETRACHLORIDE-INDUCED LIPID-PEROXIDATION IN LIVER-MICROSOMES FROM DEHYDROEPIANDROSTERONE-PRETREATED RATS

Dehydroepiandrosterone (DHEA), a lipid soluble steroid, administered t o rats (100 mg/kg b.wt) by a single intraperitoneal injection, increas es to twice its normal level in the liver microsomes. Microsomes so en riched become resistant to lipid peroxidation induced by incubation wi th carbon tetrachloride in the presence of a NADPH-regenerating system : also the lipid peroxidation-dependent inactivation of glucose-6-phos phatase and gamma-glutamyl transpetidase due to the haloalkane are pre vented. Noteworthy, the liver microsomal drug-metabolizing enzymes and in particular the catalytic activity of cytochrome P(450)IIE1, respon sible for the CCl4-activation, are not impaired by the supplementation with the steroid. Consistently, in DHEA-pretreated microsomes the pro tein covalent binding of the trichloromethyl radical (CCl3 degrees), i s similar to that of not supplemented microsomes treated with CCl4. It thus seems likely that DHEA protects liver microsomes from oxidative damage induced by carbon tetrachloride through its own antioxidant pro perties rather than inhibiting the metabolism of the toxin.