A COMPARISON OF THE ANTIHEPATOTOXIC ACTIVITY BETWEEN GLYCYRRHIZIN ANDGLYCYRRHETINIC ACID

A comparison of antihepatotoxic activities between glycyrrhizin (18 be ta-GL) and its genuine aglycone, glycyrrhetinic acid (18 beta-GA), was carried out using in vivo and in vitro assay methods. The oral admini stration of 18 beta-GA at 1, 24, and 48 h before D-galactosamine (GalN ) treatment significantly reduced the increase of serum transaminase a ctivities 24h after GalN treatment, whereas 18 beta-GL did not inhibit the increase of serum transaminase activities. The intraperitoneal ad ministration of 18 beta-GA 1h before GalN treatment restored the incre ase of serum transaminase activities with lower doses than 18 beta-GL. In CCl4-induced cytotoxicity of primary cultured rat hepatocytes, 18 beta-GA protected the CCl4-induced leakage of transaminase at doses of 5 to 50 mu g/ml, whereas 18 beta-GL inhibited slightly the leakage at a dose of 1000 mu g/ml. In the same way, 18 alpha-GA, the alpha-isome r of 18 beta-GA, reduced the CCl4-induced cytotoxicity more strongly t han 18 alpha-GL. Furthermore, the adsorbability of 18 alpha,beta-GA on primary cultured rat hepatocytes was higher than that of 18 alpha,bet a-GL. These results suggest that 18 alpha,beta-GA is a more potent ant ihepatotoxic agent than 18 alpha,beta-GL, and that the potency of the antihepatotoxic compounds parallels their adsorbability in hepatocytes .