Modulatory influence of noscapine on the ethanol-altered hepatic biotransformation system enzymes, glutathione content and lipid peroxidation in vivo in rats
Modulatory influence of noscapine on the ethanol-altered hepatic biotransformation system enzymes, glutathione content and lipid peroxidation in vivo in rats
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DOI：
10.1007/bf03190592
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发表时间：
2004-07-01
影响因子：
1.9
通讯作者：
Chandra, R
中科院分区：
文献类型：
--
作者：
Aneja, R;Katyal, A;Chandra, R
研究了鸦片生物碱诺斯卡平对乙醇诱导的肝脏药物代谢酶系统、谷胱甘肽含量和微粒体脂质过氧化的调节潜力。雄性Wistar大鼠口服诺斯平，剂量水平为200 mg/kg bw，并与50%乙醇（v/v）联合，连续5天。Noscapine给药与肝微粒体细胞色素P-450含量降低91%相关。noscapine给药后，nadph -细胞色素c还原酶活性下降约36%。诺斯卡平降低细胞色素P-450水平，同时血红素加氧酶活性和血清胆红素水平升高。我们的结果表明，诺斯高平和乙醇的联合剂量拮抗乙醇诱导的细胞色素P-450水平升高。用丙二醛（MDA）测定，诺斯卡平喂养大鼠与对照组相比，谷胱甘肽（GSH）含量降低，脂质过氧化作用增强。此外，诺斯卡平和乙醇共暴露产生了更明显的脂质过氧化升高和谷胱甘肽水平也显著下降。根据我们的研究结果，我们推测诺斯卡平和乙醇联合使用时脂质过氧化的显著增强是由于谷胱甘肽的消耗达到一定的临界水平。抑制谷胱甘肽- s -转移酶（GST）以及降低细胞色素P-450表明，诺斯卡平和乙醇的生物转化在急性共暴露后显着改变。
The modulatory potential of noscapine, an opium alkaloid was assessed on the ethanol-induced changes in hepatic drug metabolizing enzyme systems, glutathione content and microsomal lipid peroxidation. Noscapine was administered orally to male Wistar rats at a dose level of 200 mg/kg bw alone as well as in combination with 50% ethanol (v/v) for 5 days. Noscapine administration was associated with a similar to91% decrease in hepatic microsomal cytochrome P-450 content. A decline of similar to36% was observed in the NADPH-cytochrome c reductase activity on noscapine administration. The lowering of cytochrome P-450 levels on noscapine administration was accompanied by a concomitant increase in heme oxygenase activity as well as serum bilirubin levels. Our results indicate that the combination dosage of noscapine and ethanol antagonised the ethanol-induced elevation of cytochrome P-450 levels. Noscapine fed rats had decreased glutathione (GSH) content and enhanced lipid peroxidation compared to control rats as indexed by MDA method. Further, noscapine and ethanol coexposure produced a more pronounced elevation in lipid peroxidation and the glutathione levels also decreased significantly. We speculate on the basis of our results that the significant enhancement of lipid peroxidation on combination dosage of noscapine and ethanol is a consequence of depletion of glutathione to certain critical levels. The inhibition of glutathione-S-transferase (GST) as well as lowering of cytochrome P-450 suggests that the biotransformation of noscapine and ethanol is significantly altered following acute coexposures.