Epigallocatechin gallate alleviates mono-2-ethylhexyl phthalate-induced male germ cell pyroptosis by inhibiting the ROS/mTOR/NLRP3 pathway

作者全名："Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Shen, Lianju; Long, Chunlan; Wu, Shengde; Wei, Guanghui"

作者地址："[Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Shen, Lianju; Long, Chunlan] Chongqing Med Univ, Pediat Res Inst, Childrens Hosp, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Shen, Lianju; Long, Chunlan; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders,Childrens, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing Key Lab Pediat,Minist Educ,Key Lab Child, Chongqing 400014, Peoples R China"

通信作者："Long, CL; Wei, GH (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders,Childrens, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing Key Lab Pediat,Minist Educ,Key Lab Child, Chongqing 400014, Peoples R China."

来源：TOXICOLOGY IN VITRO

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001035733200001

JCR分区：Q3

影响因子：2.6

年份：2023

卷号：91

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：EGCG; MEHP; mTOR; Pyroptosis; Germ cell

摘要："Mono-2-ethylhexyl phthalate (MEHP) exposure is known to induce severe testicular injury via reactive oxygen species (ROS). However, few effective treatments are available for the precise treatment of MEHP-induced germ cell damage. Epigallocatechin gallate (EGCG), one of the major polyphenols in green tea, has potential antioxidant activity and can alleviate many diseases induced by oxidative stress. This study explored whether EGCG protects germ cells from MEHP-induced oxidative stress damage. Cells were treated with 400 & mu;M MEHP and 60 & mu;M EGCG for 24 h. EGCG reduced MEHP-induced ROS overgeneration in the spermatogonial cell line GC-1 and spermatocyte cell line GC-2. Western blotting and immunofluorescence showed that the MEHP+EGCG group exhibited lower nuclear factor (erythroid-derived 2)-like 2 (NRF2), heme oxygenase (decycling) 1 (HO-1), and superoxide dismutase (SOD) expression than the MEHP group. Moreover, activation of the mammalian target of rapamycin (mTOR) pathway was decreased. The expression of key factors of pyroptosis was downregulated, and interleukin-10 (IL-10) expression was reduced. Additionally, apoptosis was inhibited by EGCG. The findings indicate that EGCG protects against MEHP-induced germ cell pyroptosis by scavenging ROS, suppressing the mTOR pathway, and inhibiting pyroptosis. EGCG may thus be a potential treatment for MEHP-related spermatogenic dysfunction."

基金机构："National Natural Science Foundation of China [81771566, 82071632]; Postgraduate Research Innovation Project of Chongqing Medical University [CYB22210]; Ministry of Education Key Laboratory of Child Development and Disorders [YBRP-202114]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (grant numbers 81771566, 82071632) , the Postgraduate Research Innovation Project of Chongqing Medical University (grant number CYB22210) , and the Youth Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders (No. YBRP-202114) ."