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A single intraperitoneal injection of dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA) 17 hr before carbon tetrachloride (CCl 4 ) poisoning protects rats against liver injury induced by the haloalkane. In liver homogenates, both the increase in malondialdehyde production and the formation of fluorescent lipid peroxidation products are significantly reduced. Also, liver microsomes obtained from DHEA-pretreated rats incubated in vitro with CCl 4 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, confirming a cause-effect relationship between lipid peroxidation and hepatocyte death. Treatment with DHEA inhibits neither glucose-6-phosphate dehydrogenase activity in the cytosol, nor the microsomal mixed function oxidase system (cytochrome P450 content, aminopyrine demethylase and ethoxycoumarine 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 CCL 4 -induced liver injury through its own antioxidant activity, rather than by interfering with the metabolism of the toxin or with the tissue level of primary antioxidants.

Central nervous system damage in diabetes is caused by both cerebral atherosclerosis and the detrimental effect of chronic hyperglycaemia on nervous tissue. Hyperglycaemia is the primer of a series of cascade reactions causing overproduction of free radicals. There is increasing evidence that these reactive molecules contribute to neuronal tissue damage. Dehydroepiandrosterone (DHEA) has been reported to possess antioxidant properties. This study evaluates the oxidative status in the synaptosomal fraction isolated from the brain of streptozotocin-treated rats and the antioxidant effect of DHEA treatment on diabetic rats. Hydroxyl radical generation, hydrogen peroxide content, and the level of the reactive oxygen species was increased (P < 0.05) in synaptosomes isolated from streptozotocin-treated rats. The derangement of the oxidative status was confirmed by a low level of reduced glutathione and alpha-tocopherol. DHEA treatment (4 mg per day for 3 weeks, per os) protected the synaptosomes against oxidative damage: synaptosomes from diabetic DHEA-treated rats showed a significant decrease in reactive species (P < 0.05) and in the formation of end products of lipid peroxidation, evaluated in terms of fluorescent chromolipid (P < 0.01). Moreover, DHEA treatment restored the unsaturated fatty acid content of the membrane and the reduced glutathione and alpha-tocopherol levels to normal levels and restored membrane NaK-ATPase activity close to control levels. The results demonstrate that DHEA supplementation greatly reduces oxidative damage in synaptosomes isolated from diabetic rats and suggest that this neurosteroid may participate in protecting the integrity of synaptic membranes against hyperglycaemia-induced damage.