Estrogen reduces CCL4- induced liver fibrosis in rats

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Abstract
Chronic liver diseases, such as fibrosis or cirrhosis, are more common in men than in women. This gender difference may be related to the effects of sex hormones on the liver. The aim of the present work was to investigate the effects of estrogen on CCL(4)-induced fibrosis of the liver in rats. Liver fibrosis was induced in male, female and ovariectomized rats by CCL(4) administration. All the groups were treated with estradiol(1 mg/kg) twice weekly. And tamoxifen was given to male fibrosis model. At the end of 8 weeks, all the rats were killed to study serum indicators and the livers. Estradiol treatment reduced aspartate aminotransferase(AST), alanine aminotransferase (ALT), hyaluronic acid(HA) and type IV collagen(CIV) in sera, suppressed hepatic collagen content, decreased the areas of hepatic stellate cells (HSC) positive for alpha-smooth muscle actin (alpha-SMA), and lowered the synthesis of hepatic type I collagen significantly in both sexes and ovariectomy fibrotic rats induced by CCL(4) administration. Whereas, tamoxifen had the opposite effect. The fibrotic response of the female liver to CCL(4) treatment was significantly weaker than that of male liver. Estradiol reduces CCL(4)-induced hepatic fibrosis in rats. The antifibrogenic role of estrogen in the liver may be one reason for the sex associated differences in the progression from hepatic fibrosis to cirrhosis.