Singh A, Singh S P, Bamezai R
Human Genetics Laboratory, Jawaharlal Nehru University, New Delhi, India.
Nutr Cancer. 1996;25(1):101-10. doi: 10.1080/01635589609514431.
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.
本研究评估了槟榔碱通过对肝脏生物转化系统酶的新生期调节，对姜黄素（二阿魏酰甲烷）的化学预防功效进行翻译后修饰的潜力。姜黄素（0.4 g/kg体重/天）可使哺乳期母鼠和14或21日龄的F1代幼鼠肝脏中的谷胱甘肽-S-转移酶（GST）、酸溶性巯基（SH）、细胞色素b5和细胞色素P-450水平显著升高。槟榔碱（20 mg/kg体重/天）虽然使母鼠和哺乳幼鼠的细胞色素b5和细胞色素P-450水平显著升高，但不能调节肝脏GST和SH水平。在姜黄素+槟榔碱处理组中，肝脏GST、SH、细胞色素b5和细胞色素P-450水平显著增强。姜黄素诱导的GST和SH水平降低，而姜黄素+槟榔碱处理使细胞色素b5和细胞色素P-450水平进一步升高。与单独暴露于槟榔碱相比，暴露于姜黄素+槟榔碱时，I相酶水平的升高更为显著。哺乳期母鼠生物转化系统酶竞争潜在途径的调节可能会影响母体解毒的速率和程度，从而影响所给予的外源化合物代谢产物向哺乳新生幼鼠的传递。
