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.