Effects of Three Different Fibrates on Intrahepatic Cholestasis Experimentally Induced in Rats
نویسندگان
چکیده
Background. Activation of PPAR α modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of PPAR α agonists, fenofibrate, bezafibrate, and gemfibrozil, on acute cholestasis induced by ethinylestradiol (EE) plus chlorpromazine (CPZ) in rats. Method. 100 male albino rats (150-200 gm) were divided randomly into 10 equal groups. Control group received 1% methylcellulose vehicle; disease group received CPZ plus EE for 5 consecutive days; four groups received either ursodeoxycholic acid, fenofibrate, bezafibrate, or gemfibrozil for 7 days; 2 days before EE + CPZ, three other groups received one of the three fibrates after GW6471, a selective PPAR α antagonist in addition to EE + CPZ. The final group received GW6471 alone. Results. The three fibrates showed marked reduction (P < 0.05) in serum levels of ALP, GGT, ALT, AST, total bile acids, bilirubin, TNF α , and IL-1 β and in hepatic malondialdehyde level as well as a significant increase in bile flow rate (P < 0.05) in addition to improvements in histopathological parameters compared to diseased group. In groups which received GW6471, these effects were completely abolished with fenofibrate and partially blocked with bezafibrate and gemfibrozil. Conclusion. Short-term administration of fibrates to EE/CPZ-induced intrahepatic cholestatic rats exerted beneficial effects on hepatocellular damage and apoptosis. Fenofibrate anticholestatic effect was solely PPAR α dependent while other mechanisms played part in bezafibrate and gemfibrozil actions.
منابع مشابه
Matrine improves 17alpha-ethinyl estradiol-induced acute cholestasis in rats.
AIM To explore the effects of matrine (MT) on acute intrahepatic cholestasis induced by 17alpha-ethinyl estradiol (EE) in rats. METHODS Acute intrahepatic cholestasis in rats were induced by EE, and the effects of MT on acute intrahepatic cholestasis were explored and compared with ursodeoxycholic acid (UDCA) by serum biochemical determination and bile excretion experiments. RESULTS The ser...
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ورودعنوان ژورنال:
دوره 2013 شماره
صفحات -
تاریخ انتشار 2013