DEHYDROEPIANDROSTERONE PRETREATMENT PROTECTS RATS AGAINST THE PROOXIDANT AND NECROGENIC EFFECTS OF CARBON-TETRACHLORIDE

A single intraperitoneal injection of dehydroepiandrosterone (3beta-hy droxy-5-androsten-17-one, DHEA) 17 hr before carbon tetrachloride (CCl 4) poisoning protects rats against liver injury induced by the haloalk ane. In liver homogenates, both the increase in malondialdehyde produc tion and the formation of fluorescent lipid peroxidation products are significantly reduced. Also, liver microsomes obtained from DHEA-pretr eated rats incubated in vitro with CCl4 are less susceptible to lipid peroxidation than microsomes from normal animals. The release of liver enzymes into the blood is much reduced in DHEA-pretreated rats, confi rming a cause-effect relationship between lipid peroxidation and hepat ocyte death. Treatment with DHEA inhibits neither glucose-6-phosphate dehydrogenase activity in the cytosol, nor the microsomal mixed functi on oxidase system (cytochrome P450 content, aminopyrine demethylase an d ethoxycoumarin de-ethylase activities). In animals treated with DHEA , the liver content of total glutathione and vitamin E is not modified . These results support the hypothesis that DHEA protects against CCl4 -induced liver injury through its own antioxidant activity, rather tha n by interfering with the metabolism of the toxin or with the tissue l evel of primary antioxidants.