Hepatic protection by glycyrrhizin and inhibition of iNOS expression in concanavalin A-induced liver injury in mice

In this study, the possible protective effect of glycyrrhizin (GL), an active compound derived from licorice root, was examined on T cell-mediated liver injury in mice. Mice were subjected to liver injury by intravenous injection of concanavalin A (Con A). They had been treated with GL (i.p.) 30 min before the injection. Liver injury was estimated by measuring serum levels of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST), and by examining liver sections with hematoxylin-eosin staining. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein in the liver was determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Serum transaminases and hepatic iNOS levels increased with time after Con A treatment. Expression of iNOS mRNA in the liver was elevated for up to 8 h, and at 8 h, GL (ED50: 10.5 mg/kg) suppressed the increases in AST and ALT in response to Con A. An increase in iNOS mRNA expression and protein was inhibited by treatment with GL. Furthermore, GL inhibited cell infiltration and the degeneration of hepatocytes in the liver of Con A-treated mice. The present study suggests that the prevention by GL of Con A-induced hepatitis is due partly to the modulation of hepatic iNOS induction and of degeneration of hepatocytes.