The antiestrogen toremifene protects against alcoholic liver injury in female rats

Background/Aims: Females are generally considered to be more susceptible to alcohol-induced liver injury than males, To elucidate whether gonadal horm ones are involved, female rats were chronically treated with ethanol and wi th an antiestrogen, Methods: Ethanol was administered in a low-carbohydrate liquid diet. Estrog en action was blocked by dairy intubation of toremifene, a non-hepatotoxic second generation estrogen receptor antagonist. Results: The female rats consuming intoxicating amounts of ethanol diet for 6 weeks developed massive microvesicular/macrovesicular steatosis, frequen t inflammatory foci and spotty necrosis, Serum alanine aminotransferase inc reased 7-fold. Toremifene treatment did not affect steatosis, but significa ntly reduced inflammation and necrosis, Ethanol increased the expression of CD14 and tumor necrosis factor- (TNF) alpha mRNA and also the production o f TNF-ar by isolated Kupffer cells; but toremifene had no significant count eracting effect. However, toremifene significantly alleviated both ethanol induction of the pro-oxidant enzyme CYP2E1 and ethanol reduction of the oxi dant-protective enzyme Se-glutathione peroxidase, Conclusions: The partial protection by toremifene against ethanol-induced l iver lesions suggests a pathogenic contribution of estrogens, possibly asso ciated with an oxygen radical mediated mechanism. (C) 2001 European Associa tion far the Study of the Liver, Published by Elsevier Science B.V. All rig hts reserved.