Protective Effect of a Mixture of Aloe vera and Silybum marianum Against Carbon Tetrachloride–Induced Acute Hepatotoxicity and Liver Fibrosis

The hepatoprotective effects of ACTIValoe N-931 complex, a mixture of Aloe vera and Silybum marianum, against acute and chronic carbon tetrachloride (CCl(4))-induced liver injuries were investigated. Acute hepatotoxicity was induced by intraperitoneal injection of CCl(4) (50 microl/kg), and ACTIValoe N-931 complex at 85, 170, and 340 mg/kg was administered orally 48, 24, and 2 h before and 6 h after injection of CCl(4). Hepatotoxicity was assessed 24 h after CCl(4) treatment. Liver fibrosis was induced by intraperitoneal injection of CCl(4) for 8 weeks (0.5 ml/kg, twice per week), and mice were treated with ACTIValoe N-931 complex at 85, 170, or 340 mg/kg once a day (p.o.). In both acute hepatotoxicity and liver fibrosis, serum aminotransferase levels and lipid peroxidation were increased and the hepatic glutathione content was decreased. These changes were prevented by ACTIValoe N-931 complex. The ACTIValoe N-931 complex attenuated the increase in tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), mRNA expressions in acute hepatotoxicity. In antifibrotic experiments, tissue inhibitor of metalloprotease-1 (TIMP-1) mRNA expression was attenuated by treatment with ACTIValoe N-931 complex. The ACTIValoe N-931 complex decreased the hepatic hydroxyproline content and the transforming growth factor-beta1 levels. Our results suggest that the ACTIValoe N-931 complex has hepatoprotective effects in both acute and chronic liver injuries induced by CCl(4).