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 exposure in lactating dams and translactational exposure in neonates, to modulate the efficacy of clocimum oil as a blocking agent in chemopreventive pathway. Clocimum oil (25 or 50 microl/dam/day) induced a significant increase in the hepatic levels of phase II glutathione S-transferase (GST) and acid-soluble sulfhydryl in lactating dams and suckling neonates while the elevated 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 did 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 depressed 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, via enhanced phase I oxidative catalysis and less efficient GST/GSH conjugational detoxication, may suggest the antagonistic influence of arecoline on chemopreventive efficacy of clocimum oil.
Singh
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A
Human Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Singh
S P
SP
Bamezai
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R
D000818:Animals; D000831:Animals, Newborn; D001115:Arecoline / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D015786:Cytochromes b5 / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis; D007774:Lactation; D008054:Lipid Peroxides / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D031339:Ocimum; D010938:Plant Oils / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000032:analysis
D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D010938:Plant Oils; D013438:Sulfhydryl Compounds; D001115:Arecoline; D008315:Malondialdehyde; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; C051168:basil oil