Regulation of drug-metabolizing enzymes by local and systemic liver injuries.
Regulation of drug-metabolizing enzymes by local and systemic liver injuries.
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局部和全身肝损伤对药物代谢酶的调节
DOI：
10.1517/17425255.2016.1139574
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发表时间：
2016
影响因子：
4.3
通讯作者：
Xie W
中科院分区：
文献类型：
--
作者：
Guo Y;Hu B;Xie Y;Billiar TR;Sperry JL;Huang M;Xie W
摘要前言：药物代谢和处置是维持外源药物/药物和内生药物化学和功能动态平衡的关键。肝脏富含药物代谢酶和转运蛋白，在药物代谢和处置中起着至关重要的作用。越来越多的证据表明，许多肝脏和全身疾病可以通过调节肝脏中Dme和转运蛋白的表达和/或活性来影响药物的代谢和处置。涉及的领域：这篇综述集中在局部和全身性肝损伤对DMES的调节方面的最新进展。肝缺血再灌注(I/R)和脓毒症分别被用作局部和全身损伤的例子。还讨论了DMES的表达和活性在动物对局部和全身性肝损伤敏感性方面的相互作用。专家观点：局部和全身性肝损伤对肝脏中DMES的表达和活性有重大影响。由于疾病与药物的相互作用，了解疾病对DMES的影响具有重要的临床意义。未来的研究是必要的，以了解肝损伤调节DMES的机制。为了确定在动物身上的结果是否可以在人类患者身上复制，也迫切需要进行人体研究。
ABSTRACT Introduction: Drug metabolism and disposition are critical in maintaining the chemical and functional homeostasis of xenobiotics/drugs and endobiotics. The liver plays an essential role in drug metabolism and disposition due to its abundant expression of drug-metabolizing enzymes (DMEs) and transporters. There is growing evidence to suggest that many hepatic and systemic diseases can affect drug metabolism and disposition by regulating the expression and/or activity of DMEs and transporters in the liver. Areas covered: This review focuses on the recent progress on the regulation of DMEs by local and systemic liver injuries. Liver ischemia and reperfusion (I/R) and sepsis are used as examples of local and systemic injury, respectively. The reciprocal effect of the expression and activity of DMEs on animals’ sensitivity to local and systemic liver injuries is also discussed. Expert opinion: Local and systemic liver injuries have a major effect on the expression and activity of DMEs in the liver. Understanding the disease effect on DMEs is clinically important due to the concern of disease-drug interactions. Future studies are necessary to understand the mechanism by which liver injury regulates DMEs. Human studies are also urgently needed in order to determine whether the results in animals can be replicated in human patients.