Direct and translactational effect of arecoline alkaloid on the clocimum oil-modulated hepatic drug metabolizing enzymes in mice

The present study assesses the potential of arecoline alkaloid, by direct e xposure in lactating dams and translactational exposure in neonates, to mod ulate the efficacy of clocimum oil as a blocking agent in chemopreventive p athway. Clocimum oil (25 or 50 mu l/dam/day) induced a significant increase in the hepatic levels of phase II glutathione S-transferase (GST) and acid -soluble sulfhydryl in lactating darns and suckling neonates while the elev ated Levels of hepatic phase I cytochrome b5 (Cyt. b5) and cytochrome P-450 (P450) were observed only in the dams. Arecoline (0.6 mg/dam/day) alone di d not modulate the hepatic GST and sulfhydryl levels in either dams or pups , although significant induction was observed in the hepatic levels of Cyt. b5, P450 and malondialdehyde (MDA) in lactating dams and suckling neonates . Clocimum oil-modulated hepatic levels of phase II components were depress ed whereas phase I enzymes and lipid peroxides levels were further elevated by clocimum oil-plus-arecoline treatment. The direct or translactationally augmented levels of bioactivated species of the administered compounds, vi a enhanced phase I oxidative catalysis and less efficient GST/GSH conjugati onal detoxication, may suggest the antagonistic influence of arecoline on c hemopreventive efficacy of clocimum oil. (C) 2000 Elsevier Science Ltd. All rights reserved.