Protective Effect of Glycyrrhizin, Glycyrrhetic Acid and Matrine on Acute Cholestasis Induced by alpha-Naphthyl Isothiocyanate in Rats.

摘要

alpha-Naphthyl isothiocyanate (ANIT) is a known hepatotoxicant that causes acute cholestatic hepatitis characterized by the infiltration of neutrophils around bile ducts and necrotic hepatocytes. The effects of glycyrrhizin (GL), 18beta-glycyrrhetinic acid (GA), matrine (MT), oxymatrine (OMT), salvianolic acid B (SAB), silymarin (SI) and dexamethasone (DEX) on ANIT-induced acute cholestasis in rats were investigated. Serological and histological data demonstrated that the administration of GL, GA or MT all protected against hepatocyte injury and cholestasis induced by ANIT. Furthermore, the bile flow and the accumulative bile excretion of ketoprofen glucuronide (KPG), that were significantly suppressed by ANIT, were preserved in rats administered GL, GA or MT. DEX protected against acute cholestasis but did not protect against hepatocyte necrosis and elevated serum alanine aminotransferase levels following ANIT administration. Rats administrated OMT, SAB or SI were not resistant to ANIT toxicity. In summary, the protective effect of DEX is directed toward cholangiocytes rather than hepatocytes whereas the natural products, GA, GL and MT, exhibit significantly better protective effects against ANIT-induced liver damage including the protection of hepatocytes as well as cholangiocytes. ANIT:alpha-naphthyl isothiocyanate GL:glycyrrhizin GA:18beta-glycyrrhetinic acid MT:matrine OMT:oxymatrine SAB:salvianolic acid B SI:silymarin DEX:dexamethasone KPG:ketoprofen glucuronide RP-HPLC:reversed-phase high-performance liquid chromatography ALT:alanine aminotransferase Tbil:total bilirubin ALP:alkaline phosphatase gamma-GT:gamma-glutamyl transpeptidase.