没食子儿茶素没食子酸酯通过抑制 ROS/mTOR/NLRP3 通路缓解邻苯二甲酸二（2-乙基己基）酯诱导的雄性生殖细胞细胞焦亡。

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

机构信息

Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.

Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.

出版信息

Toxicol In Vitro. 2023 Sep;91:105626. doi: 10.1016/j.tiv.2023.105626. Epub 2023 Jun 5.

DOI:10.1016/j.tiv.2023.105626

PMID:37286014

Abstract

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 μM MEHP and 60 μM 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.

摘要

单-2-乙基己基邻苯二甲酸酯（MEHP）暴露已知通过活性氧物种（ROS）诱导严重的睾丸损伤。然而，对于 MEHP 诱导的生殖细胞损伤的精确治疗，可用的有效治疗方法很少。表没食子儿茶素没食子酸酯（EGCG）是绿茶中主要的多酚之一，具有潜在的抗氧化活性，可以缓解许多由氧化应激引起的疾病。本研究探讨了 EGCG 是否能保护生殖细胞免受 MEHP 诱导的氧化应激损伤。用 400 μM MEHP 和 60 μM EGCG 处理细胞 24 小时。EGCG 减少了精原细胞系 GC-1 和精母细胞系 GC-2 中 MEHP 诱导的 ROS 过度生成。Western blot 和免疫荧光显示，MEHP+EGCG 组的核因子（红细胞衍生 2）样 2（NRF2）、血红素加氧酶（脱环）1（HO-1）和超氧化物歧化酶（SOD）表达低于 MEHP 组。此外，雷帕霉素（mTOR）途径的激活降低。细胞焦亡的关键因子表达下调，白细胞介素 10（IL-10）表达减少。此外，EGCG 抑制细胞凋亡。这些发现表明，EGCG 通过清除 ROS、抑制 mTOR 途径和抑制细胞焦亡来防止 MEHP 诱导的生殖细胞细胞焦亡。因此，EGCG 可能是治疗 MEHP 相关生精功能障碍的一种潜在方法。