Neurotoxicity and the potential molecular mechanisms of mono-2-ethylhexyl phthalic acid (MEHP) in zebrafish

作者全名："Liu, Yiyun; Huo, Wen-Bo; Deng, Jiao-Yun; Tang, Qi-Ping; Wang, Jin-Xia; Liao, Yan-Ling; Gou, Dongzhi; Pei, De-Sheng"

作者地址："[Liu, Yiyun; Huo, Wen-Bo; Deng, Jiao-Yun; Tang, Qi-Ping; Wang, Jin-Xia; Liao, Yan-Ling; Gou, Dongzhi; Pei, De-Sheng] Chongqing Med Univ, Sch Publ Hlth, Chongqing 400016, Peoples R China"

通信作者："Pei, DS (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Chongqing 400016, Peoples R China."

来源：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001084755900001

JCR分区：Q1

影响因子：6.2

年份：2023

卷号：265

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Plasticizer; Mono-2-ethylhexyl phthalic acid; Neurotoxicity; Zebrafish

摘要："Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of plasticizer di-2-ethylhexyl phthalic acid (DEHP), and there is limited information available on the effects of MEHP on neurotoxicity. This study aims to examine the neurotoxicity of MEHP and preliminarily explore its potential molecular mechanisms. We found that MEHP impeded the growth of zebrafish embryos and the neurodevelopmental-related gene expression at envi-ronmentally relevant concentrations. MEHP exposure also induces oxidative stress response and brain cell apoptosis accompanied by a decrease in acetylcholinesterase (AChE) activity in zebrafish larvae. RNA-Seq and bioinformatics analysis showed that MEHP treatment altered the nervous system, neurogenic diseases, and visual perception pathways. The locomotor activity in dark-to-light cycles and phototaxis test confirmed the abnormal neural behavior of zebrafish larvae. Besides, the immune system has produced a large number of differentially expressed genes related to neural regulation. Inflammatory factor IL1 beta and IL-17 signaling pathways highly respond to MEHP, indicating that inflammation caused by immune system imbalance is a potential mechanism of MEHP-induced neurotoxicity. This study expands the understanding of the toxicity and molecular mechanisms of MEHP, providing a new perspective for in-depth neurotoxicity exploration of similar compounds."

基金机构："Scientific Research Foundation of Chongqing Medical University, China [R4014, R4021, R4015]; Chongqing Postdoctoral Science Foundation [2022TQ0394, CSTB2022NSCQ-BHX0641]; Chongqing Special Funding for Post-doctoral Research Projects [2022CQBSHTB1006]; Chongqing Post-doctoral Innovation Mentor Studio [X7928]"

基金资助正文："This work was supported by the Scientific Research Foundation of Chongqing Medical University (R4014, R4021, and R4015), China and Chongqing Postdoctoral Science Foundation (2022TQ0394, CSTB2022NSCQ-BHX0641), Chongqing Special Funding for Post-doctoral Research Projects (2022CQBSHTB1006), and Chongqing Post-doctoral Innovation Mentor Studio (X7928 D.S.P.)."