Possible prenatal impact of sertraline on human placental glutathione S-transferase-π

Author:

Dalmizrak O12,Kulaksiz-Erkmen G1,Ozer N12

Affiliation:

1. Department of Biochemistry, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey

2. Department of Biochemistry, Faculty of Medicine, Near East University, Nicosia, Mersin 10, Turkey

Abstract

Sertraline (SER), a tricyclic antidepressant, is considered to belong to the group of selective amine reuptake inhibitors. Its ability to cross the blood–brain barrier and transplacental transport has been reported previously. It is widely distributed in the brain and is bound to human glutathione S-transferase-π (GST-π). If SER is taken during pregnancy, it gets accumulated in the embryo and fetus, and some studies have suggested it may cause congenital malformations, thus the study of the interaction of GST-π with antidepressants is crucial. In this study, the interaction of human placental GST-π with SER in the presence of the natural ligand, reduced glutathione (GSH) and a xenobiotic ligand, 1-chloro-2,4-dinitrobenzene (CDNB) was investigated. The Vm values obtained at variable [CDNB] and variable [GSH] were 61.3 ± 2.3 and 46.4 ± 1.7 U/mg protein, respectively. The kcat and kcat/ Km values for GSH and CDNB were 3.63 × 106 s−1, 2.59 × 1010 M−1 s−1 and 4.79 × 106 s−1, 1.29 × 1010 M−1 s−1, respectively. The half maximal inhibitory concentration value for SER was 4.60 mM. At constant [CDNB] and variable [GSH] the inhibition type was linear mixed-type, with Ks, α, and Ki values of 0.14 ± 0.02, 2.90 ± 1.64, and 2.18 ± 0.80 mM, respectively. On the other hand, at fixed [GSH] and at variable [CDNB], the inhibition type was competitive, with Ki value of 0.96 ± 0.10 mM. Thus, these findings weaken the importance of the protective role of GST against toxic electrophiles in vivo in adults, but due to its immature enterohepatic system SER may accumulate in the fetus and cause congenital malformations.

Publisher

SAGE Publications

Subject

Health, Toxicology and Mutagenesis,Toxicology,General Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3