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
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
ISSN0009-2797
EISSN1872-7786
卷号399
DOI10.1016/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 ID39025286
SCOPUSEID2-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).

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