Effect of Emblica officinalis Extract on Hepatocarcinogenesis and Carcinogen Metabolism

Abstract

Emblica officinalis (E.O) extract was found to dose dependently lower the incidence of liver tumors induced by N-nitrosodiethylamine (NDEA). Control group rats (NDEA alone) had 100% tumor incidence, whereas in animals treated with E.O at a dose of 250mg/kg body weight, the incidence was 0%. The liver weight of the control group was 7.99±1.51g/100g body weight, and that of the E.O-treated group showed a dose-dependent decrease (4.90-3.50g/100g body weight). NDEA treatment also increased serum and liver γ-glutamyl transpeptidase (γ-GTP) activity to 135.5±27.9U/liter and 2.90±0.08nmol/min/mg protein, respectively; and E.O treatment reduced these levels in a dose-dependent manner (99.8-44.8U/liter and 2.25-0.38nmol/min/mg protein). The level of liver aniline hydroxylase, a P-450 enzyme, was increased by the NDEA treatment, and this increase was reduced by the administration of the E.O extract. Liver glutathione-S-transferase (GST) activity, which was increased to 1, 414±137nmol/min/mg protein by NDEA treatment, was found to be reduced in a dose-dependent manner by E.O in vivo. E.O extract was also found to inhibit aminopyrene-N-demethylase activity in vitro, with 301μg/ml as the concentration needed for 50% inhibition. The extract was also found to inhibit DNA adduct formation induced by benzo(a)pyrene [B(a)P] and aflatoxin B1 (AFB1). The concentration of E.O extract required for 50% inhibition of microsome-catalyzed B(a)P adduct formation was 280μg/ml; and that for AFB1 adduct formation, 120μg/ml. The results of the present study indicate that E.O extract can interfere with the metabolism of NDEA and inhibit liver tumor development by this carcinogen, suggesting its use in the prevention of hepatocarcinogenesis.