College of Veterinary Medicine, Sichuan Province Key Laboratory of Animal Disease and Human Health, Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
College of Life Since and Technology, Southwest Minzu University, Chengdu, Sichuan 610041, China.
Oxid Med Cell Longev. 2019 Feb 28;2019:5769752. doi: 10.1155/2019/5769752. eCollection 2019.
Deoxynivalenol (DON) is a common contaminant of grain worldwide and is often detected in the human diet and animal feed. Selenium is an essential trace element in animals. It has many biological functions. The role of selenium in the body is mainly orchestrated by selenoprotein. Glutathione peroxidase (GPx) also exists widely in the body and has attracted much attention due to its high antioxidant capacity. In order to explore the effect of the GPx1 gene on toxicity of DON, in this study, we overexpressed or knockdown GPx1 in porcine splenic lymphocytes, then added different concentrations of DON (0.1025, 0.205, 0.41, and 0.82 g/mL) and sodium selenite (2 mol/L) to the culture system. Using various techniques, we detected antioxidant function, free radical content, cell apoptosis, and methylation-related gene expression to explore the effect of GPx1 expression on DON-induced cell damage. We also explored whether selenium can antagonize the toxicity of DON in these two cell models and revealed the protective effect of sodium selenite on DON-induced cell damage in GPx1-overexpressing or knockdown splenic lymphocytes. Finally, our findings revealed the following: (1) GPx1 can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes. (2) NaSeO (2 mol/L) can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes, and this effect is more significant in GPx1-overexpressing cells than in GPx1-knockdown cells. (3) DON can cause oxidative damage, apoptosis, and methylation injury in GPx1-overexpressing or knockdown pig splenic lymphocytes in a concentration-dependent manner. (4) NaSeO (2 mol/L) can antagonize the toxic effect of DON on GPx1-overexpressing or knockdown pig splenic lymphocytes. Our findings may have important implications for food/feed safety, human health, and environmental protection.
脱氧雪腐镰刀菌烯醇（DON）是一种常见的谷物污染物，在人类饮食和动物饲料中经常被检测到。硒是动物必需的微量元素。它具有许多生物学功能。硒在体内的作用主要由硒蛋白协调。谷胱甘肽过氧化物酶（GPx）也广泛存在于体内，由于其具有高抗氧化能力而备受关注。为了探讨 GPx1 基因对 DON 毒性的影响，本研究在猪脾淋巴细胞中过表达或敲低 GPx1，然后向培养体系中加入不同浓度的 DON（0.1025、0.205、0.41 和 0.82μg/ml）和亚硒酸钠（2μmol/L）。采用多种技术检测抗氧化功能、自由基含量、细胞凋亡和甲基化相关基因表达，探讨 GPx1 表达对 DON 诱导的细胞损伤的影响。还探讨了硒是否可以拮抗这两种细胞模型中 DON 的毒性，并揭示了亚硒酸钠对 GPx1 过表达或敲低脾淋巴细胞中 DON 诱导的细胞损伤的保护作用。最终发现：（1）GPx1 可以调节猪脾淋巴细胞的抗氧化能力、凋亡率和 DNA 甲基化相关基因的表达。（2）NaSeO（2μmol/L）可以调节猪脾淋巴细胞的抗氧化能力、凋亡率和 DNA 甲基化相关基因的表达，这种作用在 GPx1 过表达细胞中比在 GPx1 敲低细胞中更为明显。（3）DON 可以浓度依赖的方式引起 GPx1 过表达或敲低猪脾淋巴细胞的氧化损伤、凋亡和甲基化损伤。（4）NaSeO（2μmol/L）可以拮抗 DON 对 GPx1 过表达或敲低猪脾淋巴细胞的毒性作用。本研究结果可能对食品安全/饲料安全、人类健康和环境保护具有重要意义。
