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

Hepatic injury leading to hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades. Because APAP-induced liver injury is clinically relevant, well studied, and can be rapidly induced in vivo with a single dose, it has become a standard model in the pharmacotoxicological liver researches. In particular, APAP overdose in rodents is frequently used to test the hepatoprotective potential of herbal and non-herbal therapeutics. The present study focused on the elucidation of the potential protective effects of hamamelis extract and pranlukast against acetaminophen-induced hepatotoxicity. Silymarin was used as a standard hepatoprotective agent. A single dose of acetaminophen (800 mg\kg), injected intraperitoneally to male rats, caused a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver contents of malondialdehyde (MDA), hepatic tumor necrosis factor (TNF)-Ü and cytochrome-c (Cyt-c), in addition to hepatic activities of lipoxygenase (5-LOX), caspase-3 and myeloperoxidase (MPO as compared with the control group, while it significantly decreased reduced glutathione (GSH) content, as well as superoxide dismutase (SOD) activity. On the other hand, pre-administration of each of hamamelis extract (200 mg\kg\b.w), pranlukast (10 mg\kg\b.w) and silymarin (100 mg\kg\b.w) orally for 15 consecutive days significantly ameliorated the liver injury as exhibited by the histopathological investigation confirmed by the effect on the measured biochemical parameters

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