Effect of cholecystectomy on bile acids as well as relevant enzymes and transporters in mice: Implication for pharmacokinetic changes of rifampicin

doi:10.1016/j.ejps.2016.09.006

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	Effect of cholecystectomy on bile acids as well as relevant enzymes and transporters in mice: Implication for pharmacokinetic changes of rifampicin
	Zhang, F; Qin, HY; Zhao, YS; Wei, YH; Xi, LL; Rao, Z; Zhang, JP; Ma, YR; Duan, YT; Wu, XN
刊名	EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
	2017
卷号	96 页码:141-153
关键词	Bile acids Cholecystectomy Enzymes Nuclear reporters Pharmacokinetics Transporters
ISSN号	0928-0987
DOI	10.1016/j.ejps.2016.09.006
文献子类	Article
英文摘要	Background and purpose: Long-termmedical consequences of cholecystectomy are believed to be uncommon. It has been reported that bile acids (BAs) changed after cholecystectomy. As important signaling molecules, the alternations of BAs might favour the regulatory effect on enzymes and transporters involved in BAs physiological homeostasis at the transcriptional level, which could lead to pharmacokinetic changes of drugs. Here, we determined the effect of cholecystectomy on BAs, relevant enzymes and transporters and pharmacokinetic parameters of rifampicin, and explored the potential mechanisms at the transcriptional regulatory level via nuclear receptors. Methods: Parameters of BAs in different specimens, mRNA and protein expression of enzymes, transporters and nuclear receptors that relate to BAs homeostasis in liver and ileum, and the pharmacokinetic character of rifampicin were measured in sham-operated and cholecystectomized mice. Key results: Cholecystectomy associated with considerable decreased BAs pool size that could attribute to increased fecal excretion. Most notably, as the Fxr and Pxr ligands, the alternations of hepatic and ileal individual BAs affected expression of enzymes Cyp3a11 and transporters Ntcp and Bsep in liver and Asbt in ileum significantly following cholecystectomy. Eventually, the rifampicin bioavailability was improved with depressed clearance in mice without gallbladders. Conclusion: As natural ligands for Fxr and Pxr, the alternations of individual BAs lead to the regulation of hepatic and ileal relevant enzymes and transporters after cholecystectomy. Especially, the down-regulation of hepatic Cyp3a11 suggests that undesirable pharmacokinetic alternations of drugs especially Cyp3a11 substrates like rifampicin might occur in phase with cholecystectomy. (C) 2016 Elsevier B.V. All rights reserved.
学科主题	Pharmacology & Pharmacy
出版地	AMSTERDAM
资助项目	国家自然科学基金项目
项目编号	National Natural Science Foundation of China [81373494, 21305057]
语种	英语
WOS记录号	WOS:000390698200018
资助机构	NSFC
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/189094]
专题	药学院_期刊论文
通讯作者	Wu, XN (reprint author), Lanzhou Univ, Hosp 1, Dept Pharm, 1 Donggang West Rd, Lanzhou, Gansu, Peoples R China.
推荐引用方式 GB/T 7714	Zhang, F,Qin, HY,Zhao, YS,et al. Effect of cholecystectomy on bile acids as well as relevant enzymes and transporters in mice: Implication for pharmacokinetic changes of rifampicin[J]. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,2017,96:141-153.
APA	Zhang, F.,Qin, HY.,Zhao, YS.,Wei, YH.,Xi, LL.,...&Wu, XN .(2017).Effect of cholecystectomy on bile acids as well as relevant enzymes and transporters in mice: Implication for pharmacokinetic changes of rifampicin.EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,96,141-153.
MLA	Zhang, F,et al."Effect of cholecystectomy on bile acids as well as relevant enzymes and transporters in mice: Implication for pharmacokinetic changes of rifampicin".EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 96(2017):141-153.