{"title":"Silibinin attenuates 3-nitropropionic acid-induced ovarian toxicity by alleviating oxidative stress and granulosa cell apoptosis.","authors":"Yedan Gai, Wenhao Wu, Haoyu Wang, Yuqing Li, Changbo Li, Yingyu Wang, Yaolu Zhao, Jianmin Hu, Xinhong Luan","doi":"10.1016/j.reprotox.2025.109027","DOIUrl":null,"url":null,"abstract":"<p><p>3-Nitropropionic acid (3-NP), a mycotoxin present in various plants and fungi, poses significant reproductive health risks to animals and humans through food chains contamination. This study aimed to explore the protective effects and mechanisms of silibinin, a bioactive flavonoid derived from the herbal plant Silybum marianum, against 3-NP-induced reproductive toxicity. Our findings demonstrated that silibinin treatment significantly alleviated 3-NP-induced ovarian follicular atresia and preserved ovarian histoarchitecture. Furthermore, it attenuated oxidative stress induced by 3-NP. Molecular analyses through qPCR and Western blot revealed that silibinin upregulated Bax and Caspase-3 expressions while downregulating Bcl-2 expression in the ovaries compared to the 3-NP group. Immunohistochemistry analysis of CASPASE-3 demonstrated that silibinin significantly inhibited 3-NP-induced apoptosis, predominantly in granulosa cells. Additionally, Western blot analyses showed that silibinin suppressed 3-NP-induced activation of JNK and ERK phosphorylation, downregulated KEAP1 expression, and upregulated NRF2 nuclear translocation in the ovary. Overall, our results indicate that silibinin effectively alleviated 3-NP-induced ovarian oxidative damage by modulating the JNK/ERK signaling pathways and activating the KEAP1/NRF2 signaling pathway. These findings suggest that silibinin may have potential therapeutic application for mitigating 3-NP-induced reproductive toxicity in animal husbandry and the veterinary industry.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109027"},"PeriodicalIF":2.8000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.reprotox.2025.109027","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
3-Nitropropionic acid (3-NP), a mycotoxin present in various plants and fungi, poses significant reproductive health risks to animals and humans through food chains contamination. This study aimed to explore the protective effects and mechanisms of silibinin, a bioactive flavonoid derived from the herbal plant Silybum marianum, against 3-NP-induced reproductive toxicity. Our findings demonstrated that silibinin treatment significantly alleviated 3-NP-induced ovarian follicular atresia and preserved ovarian histoarchitecture. Furthermore, it attenuated oxidative stress induced by 3-NP. Molecular analyses through qPCR and Western blot revealed that silibinin upregulated Bax and Caspase-3 expressions while downregulating Bcl-2 expression in the ovaries compared to the 3-NP group. Immunohistochemistry analysis of CASPASE-3 demonstrated that silibinin significantly inhibited 3-NP-induced apoptosis, predominantly in granulosa cells. Additionally, Western blot analyses showed that silibinin suppressed 3-NP-induced activation of JNK and ERK phosphorylation, downregulated KEAP1 expression, and upregulated NRF2 nuclear translocation in the ovary. Overall, our results indicate that silibinin effectively alleviated 3-NP-induced ovarian oxidative damage by modulating the JNK/ERK signaling pathways and activating the KEAP1/NRF2 signaling pathway. These findings suggest that silibinin may have potential therapeutic application for mitigating 3-NP-induced reproductive toxicity in animal husbandry and the veterinary industry.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.