文献类型：期刊文献

英文题名：Curcumin Enhances the Systemic Exposure of Isoniazid in Rats: Role of NAT2 in the Liver and Intestine

作者：Wang, Xiao-hua[1];Jin, Yong-wen[1];Rao, Zhi[1];Zhang, Guo-qiang[1];Zang, Kai-hong[2];Qin, Hong-yan[1]

第一作者：Wang, Xiao-hua

通信作者：Qin, HY[1]

机构：[1]Lanzhou Univ, Hosp 1, Dept Pharm, Lanzhou 730000, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Coll Pharm, Lanzhou, Peoples R China

第一机构：Lanzhou Univ, Hosp 1, Dept Pharm, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 1, Dept Pharm, Lanzhou 730000, Peoples R China.

年份：2020

卷号：16

期号：1

起止页码：10

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000507632400002)】；

基金：This study was supported by the Natural Science Foundation of Gansu Province (grant number 1606RJZA117), Foundation of Gansu Province Administration of Traditional Chinese Medicine (grant number GZK-2018-46).

语种：英文

外文关键词：Curcumin; isoniazid; N-acetyltransferase 2; pharmacokinetics; drug-drug interaction

摘要：Background and Objective: N-acetyltransferase 2 (NAT2) is the main enzyme that responsible for isoniazid (INH) metabolism, the expression and function of NAT2 play important roles in the pathogenesis of INH-induced hepatotoxicity. Concerning the potential inhibitory effect of curcumin on NAT2, it is of great importance to know the effect of curcumin on INH metabolism and evaluate enzyme-mediated drug-drug interaction. Materials and Methods: Male Wistar rats were orally administered with INH (60 mg kg(-1)) alone or in combination with curcumin (100 mg kg(-1)). The serum concentration and tissue distribution of INH and its metabolite acetylisoniazid (AcINH) were determined using HPLC-MS/MS, the protein expression and function of NAT2 in the liver and small intestine were evaluated further and molecular docking technique was also applied to explore the interaction between curcumin and NAT2. Results: Curcumin pretreatment significantly elevated the serum concentration and tissue distribution of INH accompanied with marked reduction of AcINH, the parameter AUC(0-t), t(1/2) and C-max in curcumin pretreated rats were all significantly increased, while CL/F was markedly reduced. NAT2 activity in the liver and small intestine were significantly inhibited by curcumin pretreatment. Molecular docking study showed that curcumin could locate at the hydrophobic pocket and form a strong binding to NAT2. Conclusion: Results from this study indicate that curcumin could inhibit NAT2 activity and further affect the pharmacokinetics of INH. This study may provide a cue for reducing INH-induced hepatotoxicity and improving INH potency by curcumin co-administration.