Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Estrogen-induced cholestasis is a pathological condition characterized by impaired bile flow and the accumulation of bile acids in the plasma of susceptible women, either after estrogen administration or in pregnancy. Experimental cholestasis induced by estrogen administration to rodents, mainly 17Ü-ethinylestradiol (EE), causes liver injury through mechanisms including oxidative stress and structural or functional damage of the hepatocyte membrane, due to the detergent properties of bile acids. The present study focused on the elucidation of the potential protective effects of lycopene and colesevalm against estradiol induced cholestasis. Useful effects of antioxidants in cholestasis have been reported in several experimental models. Being a natural antioxidant carotenoid, lycopene is suggested to be one of the most powerful antioxidants. Colesevelam is a bile acid sequestrant, which interrupt the enterohepatic circulation of bile acids by binding with them in the intestine to form an insoluble complex that is excreted in the feces. Silymarin was used as a standard reference hepatoprotective agent. Estradiol administrated subcutaneously (5mg/kg) for 18 days to male rats, caused significant increases in total bile acid (TBA), serum alanine aminotranferase (ALT), aspartate aminotrasnferase (AST),alkaline phosphatase (ALP), gamma glutamyle transferase (GGT), total bilirubin (T.Bil), liver contents of malondialdehyde (MDA), hepatic tumor necrosis factor (TNF)-Ü and myeloperoxidase (MPO) in liver tissue as compared with the control group while significantly decreased total protein ,albumin and reduced glutathione (GSH) content

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