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

Hepatic encephalopathy (HE) is a syndrome resulting from acute or chronic liver failure. The pathogenesis of HE is still not well understood. The main hypothesis suggests a state of hyperammonemia which is responsible for both direct and indirect alterations in cerebral metabolism. In this study, the effect of milk-derived alpha-lactalbumin (LAC) and vitamin C (vit.C) was evaluated in thioacetamide (TAA)-induced HE model. Animals were divided into seven equal groups; rats were treated with TAA (100 mg/kg, i.p.) or saline thrice weekly for six weeks to induce HE then treated orally with LAC (100 or 150 mg/kg), vit. C (500 mg/kg) or their combination daily for two weeks. Twenty-four hours after last treatment sera, liver and brain samples were collected to assess the serum ammonia level, activities of alanine transaminase (ALT), and aspartate transaminase (AST), brain and liver oxidative stress parameters as well as histopathological investigations. TAA-encephalopathic rats experienced increases in serum activities of ALT and AST as well as serum levels of ammonia. Furthermore, TAA-induced HE exerted hepatic and brain oxidative damage as indicated by an increase in lipid peroxidation marker, malondialdehyde (MDA), a decrease in reduced glutathione (GSH) concentration and a decrease in superoxide dismutase (SOD) activity as well as increased nitrite levels. Eventually, TAA caused distortion of hepatic and brain architecture as shown by a histopathological examination. Treatment of encephalopathic rats with LAC either alone or combined with vit.C resulted in improved liver functions by decline in serum AST and ALT activities and reduction in serum ammonia level

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