Effect of arecoline on the curcumin-modulated hepatic biotransformation system enzymes in lactating mice and translactationally exposed F1 pups.

Abstract

The present study assesses the potential of arecoline alkaloid to translactationally modify the chemopreventive efficacy of curcumin (diferuloyl methane) via neonatal modulation of hepatic biotransformation system enzymes. Curcumin (0.4 g/kg body wt/day) induced a significant increase in the hepatic levels of glutathione-S-transferase (GST), acid-soluble sulfhydryl (SH), cytochrome b5, and cytochrome P-450 in lactating dams and F1 pups at 14 or 21 days. Arecoline (20 mg/kg body wt/day) could not modulate the hepatic GST and SH levels, although significant induction was observed in the levels of cytochrome b5 and cytochrome P-450 in dams and suckling pups. Significant enhancement of hepatic GST, SH, cytochrome b5, and cytochrome P-450 levels was observed in groups treated with curcumin+arecoline. Curcumin-induced levels of GST and SH were depressed whereas cytochrome b5 and cytochrome P-450 were further elevated by curcumin+arecoline treatment. The elevated levels of Phase I enzymes were more significant with exposure to curcumin+arecoline than with arecoline exposure alone. Modulation in competing potential pathways of biotransformation system enzymes in lactating dams may affect the rate and extent of maternal detoxication and thus influence the passage of metabolites of administered xenobiotics to the suckling neonate.