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

Abstract

α-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), 18β-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.

Abbreviations

ANIT:α-naphthyl isothiocyanate

GL:glycyrrhizin

GA:18β-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

γ-GT:γ-glutamyl transpeptidase

Key words

Hibiscus sabdariffa - Malvaceae - antihypertensive - standardized herbal medicinal product - complementary and alternative medicine

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