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 (R) N-931 complex, a mixture of Aloe vera and Silybum marianum, against acute and chronic carbon tetrachloride (CCl4)-induced liver injuries were investigated. Acute hepatotoxicity was induced by intraperitoneal injection Of CCl4 (50 mu l/kg), and ACTIValoe (R) 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 CCl4. Hepatotoxicity was assessed 24 h after CCl4 treatment. Liver fibrosis was induced by intraperitoneal injection Of CCl4 for 8 weeks (0.5 ml/kg, twice per week), and mice were treated with ACTIValoe (R) 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 (R) N-931 complex. The ACTIValoe (R) N-931 complex attenuated the increase in tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (WOS), 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 (R) N-931 complex. The ACTIValoe (R) N-931 complex decreased the hepatic hydroxyproline content and the transforming growth factor-beta 1 levels. Our results suggest that the ACTIValoe (R) N-931 complex has hepatoprotective effects in both acute and chronic liver injuries induced by CCl4.