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活性氧自由基/JAK2/STAT3 信号通路在邻苯二甲酸二丁酯诱导的睾酮合成抑制中的作用及番茄红素的拮抗作用。

Role of ROS/JAK2/STAT3 signaling pathway in di-n-butyl phthalate-induced testosterone synthesis inhibition and antagonism of lycopene.

机构信息

Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.

College of Food Science, Northeast Agricultural University, Harbin, 150030, China.

出版信息

Food Chem Toxicol. 2023 May;175:113741. doi: 10.1016/j.fct.2023.113741. Epub 2023 Mar 21.

DOI:10.1016/j.fct.2023.113741
PMID:36958386
Abstract

Di-n-butyl phthalate (DBP) causes adverse effects on male reproduction, especially testosterone synthesis inhibition. However, the specific mechanism of DBP-induced testosterone synthesis inhibition and its effective intervention measures of prevention and treatment are scarce presently. Lycopene (LYC) plays beneficial roles in male infertility because of its antioxidant activity. Nevertheless, it is unclear whether LYC could prevent DBP-induced male reproductive toxicity. By in vitro and in vivo investigations, this study demonstrated that DBP activated ROS/JAK2/STAT3 signaling pathway, promoted mitophagy and apoptosis, which in turn inhibited testosterone synthesis. Additionally, another major finding was that LYC supplement could reverse the above change, presenting as the restraint of ROS/JAK2/STAT3 signaling pathway, reduction of mitophagy and apoptosis, and improvement of testosterone synthesis. Our study facilitates deeper understandings of the mechanism in DBP-induced testosterone synthesis inhibition, and identifies LYC as the effective prevention and control strategies for DBP poisoning.

摘要

邻苯二甲酸二正丁酯(DBP)对男性生殖功能具有不良影响,尤其是对睾丸酮合成的抑制作用。然而,目前关于 DBP 诱导的睾丸酮合成抑制的具体作用机制及其有效的防治干预措施还很缺乏。番茄红素(LYC)由于其抗氧化活性,对男性不育症具有有益作用。然而,目前尚不清楚 LYC 是否可以预防 DBP 引起的男性生殖毒性。通过体外和体内研究,本研究表明 DBP 激活了 ROS/JAK2/STAT3 信号通路,促进了细胞自噬和细胞凋亡,从而抑制了睾丸酮的合成。此外,另一个主要发现是,LYC 补充可以逆转上述变化,表现为 ROS/JAK2/STAT3 信号通路的抑制、细胞自噬和细胞凋亡的减少以及睾丸酮合成的改善。本研究有助于深入了解 DBP 诱导的睾丸酮合成抑制的作用机制,并确定 LYC 是 DBP 中毒的有效防治策略。

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