The Effects of 10 Triterpenoid Compounds on Experimental Liver Injury in Mice

Abstract

The Effects of 10 Triterpenoid Compounds on Experimental Liver Injury in Mice. Liu, J., Liu, Y., Mao, Q., and Klaassen, C. D. (1994). Fundam. Appl. Toxicol. 22, 34-40.The purpose of this study was to compare the hepatoprotective effects of 10 oleanane-type triterpenoid compounds on three known hepatotoxicants in mice. These compounds include oleanolic acid, ursolic acid, uvaol, α-hederin (α-H), hederagenin, glycyrrhizin, 18α-glycyrrhetinic acid (α-GA), 18β-glycyrrhetinic acid (β-GA), 19α-hydroxyl asiatic acid 28-O-β-d-glucoside (HAG), and 19α-hydroxyl asiatic acid (HA). They were administrated sc for 3 days at 200 μmol/kg, except for α-H, which was given at 100 μmol/kg for 2 days. Acute liver injury was produced in male CF-1 mice by CCl4 (15 μl/kg, ip), acetaminophen (500 mg/kg, ip), and cadmium chloride (3.7 mg/kg, iv). Liver damage was assessed by serum activities of alanine aminotransferase and sorbitol dehydrogenase, as well as by histopathological examination. α-Hederin, ursolic acid, and oleanolic acid markedly decreased the toxicity produced by all three hepatotoxicants. Uvaol significantly decreased CCl4- and Cd-induced hepatotoxicity, but had no effect on acetaminophen toxicity. Glycyrrhizin, α-GA, and β-GA decreased acetaminophen-induced liver injury, whereas hederagenin, HAG, and HA did not protect against any of the hepatotoxicants. In addition, α-hederin, ursolic acid, oleanolic acid, and uvaol increased hepatic metallothionein levels by 87-, 48-, 28-, and 10-fold, respectively, as determined by the Cd/hemoglobin assay. In conclusion, among the 10 triterpenoid compounds examined, α-hederin, ursolic acid, and oleanolic acid appear to be the most effective in protecting against CCl4-, acetaminophen-, and Cd-induced liver injury.