Abstract

N–NITROSODIETHYLAMINE INDUCED HEPATOCARCINOGENESIS IN RATS: POSSIBLE CHEMOPREVENTION MECHANISM BY MORINDA CITRIFOLIA (ROOT)

*Ranju Pal, Thirumoorthy N., Govind Mohan

ABSTRACT

In the present investigation the effects of morinda citrifolia root extract (MCRExt) on hepatic marker enzymes [AST, ALT, ALP], total bilirubin, total protein, lipid peroxides and antioxidants [reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-Stransferase (GST), superoxide dismutase (SOD), catalase (CAT), vitamin-E and C] during N-nitrosodiethylamine (NDEA) – induced hepatocarcinogenesis in wistar albino male rats were studied. Rats were divided into five groups of six animals. The animals in the groups 1 and 3 were normal control and MCRExt control, respectively. Groups 2, 4 and 5 were administered with 0.01% NDEA in drinking water for 15 weeks to induce hepatocellular carcinoma (HCC). Starting 1 week prior to NDEA administration group 4 animals were treated with MCRExt in diet for 16 weeks, 5 weeks after NDEA administration group 5 animals were treated with MCRExt and continued till the end of the experimental period (16 weeks). After the experimental period the body weight, relative liver weight, number of nodules, size of nodules were assessed. In group 2 hepatocellular carcinoma induced animals there was an increase in the number of nodules, relative liver weight. The levels of lipid peroxides were elevated with subsequent decrease in the body weight, total protein, GSH, SOD, CAT, GPx, GST, Vitamin E & C. In contrast, MCRExt +NDEA treated groups 4 and 5 animals showed a significant decrease in the number of nodules with concomitant decrease in the lipid peroxidation status. The levels of GSH, total protein and the activities of antioxidant in liver were improved when compared with hepatocellular carcinoma induced group 2 animals. A significant increase in the activities of serum AST, ALT, ALP and total bilirubin was observed in NDEA treated rats when compared with control animals. MCRExt +NDEA treated groups 4 and 5 animals showed significant decrease in the activities of these enzymes when compared with NDEA treated animals. The pretreatment effect of MCRExt was higher compared to post-treatment. These findings suggest that MCRExt suppresses NDEA induced hepatocarcinogenesis by modulating the antioxidant defense status of the animals.

Keywords: Antioxidants; N-nitrosodiethylamine; Hepatocellular carcinoma; morinda citrfolia; Flavonoids; Lipid peroxidation; hepatic marker enzymes.