Protective effect of mixture of Aloe and Silybum on carbon tetrachloride-induced acute hepatotoxicity and liver fibrosis

The present study was carried out to investigate the hepatoprotective effects of mixture of aloe and silybum against acute and chronic carbon tetrachloride (CCl₄)-induced liver injury. Acute liver damage was induced by intraperitoneal injection of CCl₄ (50µl/kg) and mixture of aloe and silybum was administered orally 48h, 24h, 2h before and 6h after the injection of CCl₄. Hepatotoxicity was assessed 24h after the CCl₄ treatment. Chronic liver damage was induced by intraperitoneal injection of CCl₄ for 5 weeks (0.5ml/kg, twice per week) and mixture of aloe (70mg/kg) and silybum (100mg/kg) was treated once a day (p.o). In both acute hepatotoxicity and liver fibrosis induced by CCl₄, serum alanine aminotransferase (ALT; 2112.7±263 IU/L; 1208.9±99.8 IU/L), aspartate aminotransferase (AST) levels (1086.7±165.4 IU/L; 2188.8±270.2 IU/L) and lipid peroxidation (MDA; 0.52±0.03 nmol/mg protein; 0.607±.0.09 nmol/mg protein) were increased and the content of hepatic glutathione (GSH; 5.5±0.4µmol/g liver; 5.2±0.2µmol/g liver) were decreased. These changes were prevented by mixture of aloe and silybum (p<0.05). The mixture of aloe and silybum attenuated the increase in the expression of tumor necrosis factor-α (72% of CCl₄ alone, p<0.05), inducible nitric oxide synthase (78%, of CCl₄ alone, p<0.05), cyclooxygenase-2 mRNA (72% of CCl₄ alone, p<0.05), proinflammatory mediators in acute hepatotoxicity. In antifibrotic experiments, the expression of tissue inhibitor of metalloprotease-1 mRNA (1200-fold increase vs. control) was attenuated by the mixture of aloe and silybum treatment (p<0.01). The mixture of aloe and silybum decreased the hepatic hydroxyproline contents (69% of CCl₄ alone, p<0.05) and transforming growthfactor-beta1 level (64% of CCl₄ alone, p<0.05). Our results suggest that the mixture of aloe and silybum has hepatoprotective effect in both acute and chronic liver injury induced by CCl₄.