...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of applied toxicology >Effects of choline-deprivation on paracetamol- or phenobarbital-induced rat liver metabolic response.
【24h】

Effects of choline-deprivation on paracetamol- or phenobarbital-induced rat liver metabolic response.

机译：胆碱剥夺对对乙酰氨基酚或苯巴比妥诱导的大鼠肝脏代谢反应的影响。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Choline is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions in both humans and rodents. Various pathophysiological states have been linked to choline deprivation (CD). The aim of the present study was to determine the effect of CD upon biochemical, histological and metabolic alterations induced by drugs that affect hepatic functional integrity and various drug metabolizing systems via distinct mechanisms. For this purpose, paracetamol (ACET) or phenobarbital (PB) were administered to male Wistar rats that were fed with standard rodent chow (normally fed, NF) or underwent dietary CD. The administration of ACET increased the serum aspartate aminotransferase levels in NF rats, while CD restricted this increase. On the other hand, ACET suppressed alkaline phosphatase levels only in CD rats. Moreover, CD prevented the PB-induced increase of the mitotic activity of hepatocytes. The administration of ACET down-regulated CYP1A2 and CYP2B1 expression in CD rats, while up-regulating them in NF rats. The administration of PB suppressed CYP1A2 apoprotein levels in CD rats, whereas the drug had no effect on NF rats. The PB-induced up-regulation of CYP2B, CYP2E1 and CYP1A1 isozymes was markedly higher in CD than in NF rats. In addition, PB increased glutathione-S-transferase activity only in CD rats. Hepatic glutathione content (GSH) was suppressed by ACET in NF rats, whereas the drug increased GSH in CD rats. Our data suggest that CD has a significant impact on the hepatic metabolic functions, and in particular on those related to drug metabolism. Thus, CD may modify drug effectiveness and toxicity, as well as drug-drug interactions, particularly those related to ACET and PB. Copyright (c) 2008 John Wiley & Sons, Ltd.
机译：胆碱是一种必需营养素，似乎与人类和啮齿动物的各种代谢反应和功能有关。各种病理生理状态与胆碱剥夺（CD）有关。本研究的目的是确定CD对药物的生化，组织学和代谢改变的影响，这些药物通过不同的机制影响肝功能完整性和各种药物代谢系统。为此，对雄性Wistar大鼠饲喂扑热息痛（ACET）或苯巴比妥（PB），以标准啮齿动物饲料（正常喂养，NF）或饮食饮食CD喂养雄性Wistar大鼠。 ACET的使用增加了NF大鼠的血清天冬氨酸转氨酶水平，而CD限制了这种增加。另一方面，ACET仅在CD大鼠中抑制碱性磷酸酶水平。而且，CD阻止了PB诱导的肝细胞有丝分裂活性的增加。 ACET的给药在CD大鼠中下调CYP1A2和CYP2B1的表达，而在NF大鼠中上调它们的表达。 PB的给药抑制了CD大鼠的CYP1A2载脂蛋白水平，而该药物对NF大鼠没有影响。 PB诱导的CYP2B，CYP2E1和CYP1A1同工酶的上调在CD中明显高于NF大鼠。另外，PB仅在CD大鼠中增加谷胱甘肽-S-转移酶活性。 ACET可抑制NF大鼠肝谷胱甘肽含量（GSH），而CD大鼠可增加GSH。我们的数据表明CD对肝代谢功能，特别是与药物代谢相关的功能有重大影响。因此，CD可能会改变药物的有效性和毒性，以及药物与药物之间的相互作用，特别是与ACET和PB有关的相互作用。版权所有（c）2008 John Wiley＆Sons，Ltd.

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号