Altered enzyme profile is possibly related to hepatocarcinogenesis by clofibrate

Sequential analysis of a few biochemical markers was carried out in rat liver exposed to the hypolipidemic drug, clofibrate. A transformation marker, gamma-glutamyltranspeptidase (GGT), proliferation markers, polyamines, differentiation markers, arginase and ornithine transaminase (OTA), were chosen for the study. GGT activity was significantly reduced with an increase in glutathione concentration. Polyamine synthesis was markedly elevated 5 h following clofibrate administration. However, chronic exposure evoked only a moderate increase in polyamine profile. Hepatic arginase activity decreased significantly during the course of drug treatment. Progressive decrease in OTA, accompanied by hyperornithinemia, suggested decreased catabolism of ornithine. It is felt that these effects of clofibrate on enzyme systems unrelated to its lipid lowering action have far-reaching implications in hepatocarcinogenesis.