Functional assessment of CYP3A4 and CYP2C19 genetic polymorphisms on the metabolism of clothianidin in vitro

doi:10.1016/j.cbi.2024.111154

科研成果详情

题名	Functional assessment of CYP3A4 and CYP2C19 genetic polymorphisms on the metabolism of clothianidin in vitro
作者	Hu, Yingying1; Ye, Zhize 2; Wu, Hualu1; Chen, Xiaohai 1; Xia, Hailun1; Cai, Jian-ping 3; Hu, Guo-xin4; Xu, Ren-ai1
发表日期	2024-08-25
发表期刊	CHEMICO-BIOLOGICAL INTERACTIONS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Clothianidin Variants Metabolism
其他关键词	ALLELIC VARIANTS ; RAPID METABOLIZER ; IDENTIFICATION ; GENOTYPE ; EXPOSURE ; ENZYMES ; RISK
摘要	Clothianidin, classified as a second-generation neonicotinoid, has achieved extensive application due to its high efficacy against insect pests. This broad-spectrum usage has resulted in its frequent detection in environmental surveys. CYP2C19 and CYP3A4 are crucial for converting clothianidin to desmethyl-clothianidin (dm-clothianidin). The expression of these CYP450s can be significantly influenced by genetic polymorphisms. The objective of our research was to examine the catalytic effects of 27 CYP3A4 variants and 31 CYP2C19 variants on the metabolism of clothianidin within recombinant insect microsomes. These variants were assessed through a wellestablished incubation procedure. In addition, the concentration of its metabolite dm-clothianidin was quantified by employing an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Lastly, the kinetic parameters of these CYP3A4 and CYP2C19 variants were calculated by applying Michaelis-Menten kinetic analysis to fit the data. The observed changes in enzyme activity were related to the metabolic transformation of clothianidin to dm-clothianidin. In the CYP2C19 metabolic pathway, one variant (CYP2C19.23) showed no notable change in intrinsic clearance (CLint), four variants (CYP2C19.29, .30, .31 and L16F) demonstrated a marked increase in CLint(110.86-183.46 %), and the remaining 25 variants exhibited a considerable decrease in CLint(26.38-89.79 %), with a maximum decrease of 73.62 % (CYP2C19.6). In the CYP3A4 metabolic pathway, 26 variants demonstrated significantly reduced CLint(10.54-52.52 %), with a maximum decrease of 89.46 % (CYP3A4.20). Our results suggested that most variants of CYP3A4 and CYP2C19 significantly altered the enzymatic activities associated with clothianidin metabolism to various degrees. This study provides new insights into assessing the metabolic behavior of pesticides and delivers crucial data that can guide clinical detoxification strategies.
出版者	ELSEVIER IRELAND LTD
ISSN	0009-2797
EISSN	1872-7786
卷号	399
DOI	10.1016/j.cbi.2024.111154
页数	10
WOS类目	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:001275234400001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39025286
SCOPUSEID	2-s2.0-85198991440
通讯作者地址	[Xu, Ren-ai]Wenzhou Med Univ, Affiliated Hosp 1, Nanbaixiang St, Wenzhou 325000, Zhejiang, Peoples R China. ; [Cai, Jian-ping]Chinese Acad Med Sci, Inst Geriatr Med, Key Lab Geriatr,Beijing Inst Geriatr, Beijing Hosp,Natl Ctr Gerontol,Natl Hlth Commiss, Beijing, Peoples R China. ; [Hu, Guo-xin]Wenzhou Med Univ, Inst Mol Toxicol & Pharmacol, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China.
Scopus学科分类	Toxicology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/216751
专题	附属第一医院药学院（分析测试中心）_分子药理研究与教学中心
通讯作者	Cai, Jian-ping; Hu, Guo-xin; Xu, Ren-ai
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Nanbaixiang St, Wenzhou 325000, Zhejiang, Peoples R China; 2.Shaoxing Peoples Hosp, Shaoxing, Zhejiang, Peoples R China; 3.Chinese Acad Med Sci, Inst Geriatr Med, Key Lab Geriatr,Beijing Inst Geriatr, Beijing Hosp,Natl Ctr Gerontol,Natl Hlth Commiss, Beijing, Peoples R China; 4.Wenzhou Med Univ, Inst Mol Toxicol & Pharmacol, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China
第一作者单位	附属第一医院
通讯作者单位	附属第一医院; 分子药理研究与教学中心
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Hu, Yingying,Ye, Zhize,Wu, Hualu,et al. Functional assessment of CYP3A4 and CYP2C19 genetic polymorphisms on the metabolism of clothianidin in vitro[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2024,399.
APA	Hu, Yingying., Ye, Zhize., Wu, Hualu., Chen, Xiaohai., Xia, Hailun., ... & Xu, Ren-ai. (2024). Functional assessment of CYP3A4 and CYP2C19 genetic polymorphisms on the metabolism of clothianidin in vitro. CHEMICO-BIOLOGICAL INTERACTIONS, 399.
MLA	Hu, Yingying,et al."Functional assessment of CYP3A4 and CYP2C19 genetic polymorphisms on the metabolism of clothianidin in vitro".CHEMICO-BIOLOGICAL INTERACTIONS 399(2024).