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

The purpose of this study was to evaluate the hepatotoxicity induced by co- administration of fluvastatin (F) and carbon tetrachloride (CCl4); and to investigate the hepatoprotective effect of Whey protein isolate (WPI) in F+CCl4-induced liver injury in animal model. Hepatotoxicity was induced by F (4 or 8 mg/kg, p.o.) and CCl4 (0.8ml/kg, i.p, twice weekly) for 30 days in rats. Silymarin (50mg/kg, p.o.) or WPI (100, 200 mg/kg, p.o.) were administered for 30 days. Hepatotoxicity was assessed by alteration of serum alanine aminotransferase (ALT) aspartate aminotransferase (AST), total triglycerides (TGs) and total cholesterol (TC) levels as well as alteration of liver malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH) contents, total antioxidant capacity (TAC), superoxide dismutase (SOD) activity and hydroxyproline (Hyp) content and histoarchitecture alterations. Co-administration of fluvastatin two dose levels and CCl4 significantly elevated serum ALT, AST, TGs, TC levels, NO and MDA contents in liver homogenate. Moreover, they reduced Hyp, GSH, TAC and SOD activity.Microscopic examination showed severe vacuolar degeneration of hepatocytes, focal cellular infiltration, and complete distortion of liver tissue architecture, DNA aberration and fibrosis. WPI administration reversed the deleterious effect induced by F+CCl4. In conclusion, WPI improved the antioxidant status of hepatocytes and it had promising anti-fibrotic effect in this model

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