The antiestrogen toremifene protects against alcoholic liver injury in female rats
| Autor: | Kai O. Lindros, Helmuth Sippel, Tuomo A. Lukkari, Harri A. Järveläinen, S. Heinaro |
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| Rok vydání: | 2001 |
| Předmět: |
Selective Estrogen Receptor Modulators
Alcoholic liver disease medicine.medical_specialty Necrosis Kupffer Cells medicine.drug_class Lipopolysaccharide Receptors Estrogen receptor Biology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals RNA Messenger Toremifene Rats Wistar Liver Diseases Alcoholic Cells Cultured 030304 developmental biology Liver injury Glutathione Peroxidase Sex Characteristics 0303 health sciences Ethanol Hepatology Tumor Necrosis Factor-alpha Cytochrome P-450 CYP2E1 medicine.disease Antiestrogen Enzymes Interleukin-10 Rats 3. Good health Alcoholism Endocrinology Liver Estrogen 030220 oncology & carcinogenesis Female Steatosis medicine.symptom medicine.drug |
| Zdroj: | Journal of Hepatology. 35:46-52 |
| ISSN: | 0168-8278 |
| Popis: | Background/Aims : Females are generally considered to be more susceptible to alcohol-induced liver injury than males. To elucidate whether gonadal hormones are involved, female rats were chronically treated with ethanol and with an antiestrogen. Methods : Ethanol was administered in a low-carbohydrate liquid diet. Estrogen action was blocked by daily 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, frequent inflammatory foci and spotty necrosis. Serum alanine aminotransferase increased 7-fold. Toremifene treatment did not affect steatosis, but significantly reduced inflammation and necrosis. Ethanol increased the expression of CD14 and tumor necrosis factor- (TNF) α mRNA and also the production of TNF- α by isolated Kupffer cells, but toremifene had no significant counteracting effect. However, toremifene significantly alleviated both ethanol induction of the pro-oxidant enzyme CYP2E1 and ethanol reduction of the oxidant-protective enzyme Se-glutathione peroxidase. Conclusions : The partial protection by toremifene against ethanol-induced liver lesions suggests a pathogenic contribution of estrogens, possibly associated with an oxygen radical mediated mechanism. |
| Databáze: | OpenAIRE |
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