Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China.
Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003, Hradec Kralove, Czech Republic.
Food Chem Toxicol. 2022 Jul;165:113061. doi: 10.1016/j.fct.2022.113061. Epub 2022 Apr 27.
The mycotoxin zearalenone (ZEA) in food and feed seriously harms human and animal health. How to reduce its toxicity is an important direction of current research on food safety. This study aim to assess the effects of procyanidins (PC) on cell apoptosis caused by ZEA and to clarify the role of Nrf2 in the process. Swine testicle (ST) cells were treated with ZEA (57.5 μmol/L) and/or PC (10 mg/L) for 24 h. Cell viability was detected by CCK-8 assay. Cell apoptosis and the level of ROS were detected by flow cytometry. The expression levels of mRNA and protein was detected by qRT-PCR and western blotting. Our results showed that ZEA reduced the antioxidant capacity of the ST cells, induced the cell apoptosis and inhibited the gene and protein expression of Nrf2 and its downstream genes (ho-1,nqo1), while PC improved the cell antioxidant capacity, reduced the degree of ZEA-induced cell apoptosis and promoted the gene and protein expression of Nrf2 and its downstream genes. However, when the Nrf2 small molecule inhibitor ML385 was added, the ability of PC to inhibit ZEA-induced cell apoptosis and promote the expression of Nrf2 and its downstream genes were decreased. Our results demonstrated that ZEA induced oxidative stress and apoptosis of ST cells, which were alleviated by PC intervention via activating Nrf2 signaling pathway. This finding of this study provided a molecular basis for the clinical application of PC to prevent ZEN-caused reproductive toxicity.
真菌毒素玉米赤霉烯酮（ZEA）在食品和饲料中严重危害人类和动物健康。如何降低其毒性是食品安全研究的重要方向。本研究旨在评估原花青素（PC）对 ZEA 诱导的细胞凋亡的影响，并阐明 Nrf2 在该过程中的作用。用 ZEA（57.5μmol/L）和/或 PC（10mg/L）处理猪睾丸（ST）细胞 24h。通过 CCK-8 测定法检测细胞活力。通过流式细胞术检测细胞凋亡和 ROS 水平。通过 qRT-PCR 和 Western blot 检测 mRNA 和蛋白的表达水平。结果表明，ZEA 降低了 ST 细胞的抗氧化能力，诱导细胞凋亡，并抑制 Nrf2 及其下游基因（ho-1、nqo1）的基因和蛋白表达，而 PC 则提高了细胞抗氧化能力，降低了 ZEA 诱导细胞凋亡的程度，并促进了 Nrf2 及其下游基因的基因和蛋白表达。然而，当添加 Nrf2 小分子抑制剂 ML385 时，PC 抑制 ZEA 诱导的细胞凋亡和促进 Nrf2 及其下游基因表达的能力降低。结果表明，ZEA 诱导 ST 细胞氧化应激和凋亡，PC 通过激活 Nrf2 信号通路干预可减轻这种作用。本研究的发现为 PC 预防 ZEN 引起的生殖毒性的临床应用提供了分子基础。
