Yu Miao, Chen Liangkai, Peng Zhao, Wang Di, Song Yadong, Wang Hanying, Yao Ping, Yan Hong, Nüssler Andreas K, Liu Liegang, Yang Wei
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
Toxins (Basel). 2017 Jun 9;9(6):188. doi: 10.3390/toxins9060188.
Deoxynivalenol (DON) belongs to the type B group of trichothecenes family, which is composed of sesquiterpenoid metabolites produced by Fusarium and other fungi in grain. DON may cause various toxicities, such as cytotoxicity, immunotoxicity, genotoxicity as well as teratogenicity and carcinogenicity. In the present study, we focus on a hypothesis that DON alters the expressions of Nrf2/HO-1 pathway by inducing embryotoxicity in C57BL/6 mouse (5.0, 2.5, 1.0, and 0 mg/kg/day) and BeWo cell lines (0 and 50 nM; 3 h, 12 h and 24 h). Our results indicate that DON treatment in mice during pregnancy leads to ROS accumulation in the placenta, which results in embryotoxicity. At the same time Nrf2/HO-1 pathway is up-regulated by ROS to protect placenta cells from oxidative damage. In DON-treated BeWo cells, the level of ROS has time-effect and dose-effect relationships with HO-1 expression. Moderate increase in HO-1 protects the cell from oxidative damage, while excessive increase in HO-1 aggravates the oxidative damage, which is called in some studies the "threshold effect". Therefore, oxidative stress may be the critical molecular mechanism for DON-induced embryotoxicity. Besides, Nrf2/HO-1 pathway accompanied by the "threshold effect" also plays an important role against DON-induced oxidative damage in this process.
脱氧雪腐镰刀菌烯醇（DON）属于单端孢霉烯族毒素B组，该组由镰刀菌和谷物中其他真菌产生的倍半萜类代谢产物组成。DON可能会引发多种毒性，如细胞毒性、免疫毒性、遗传毒性以及致畸性和致癌性。在本研究中，我们聚焦于一个假说，即DON通过诱导C57BL/6小鼠（5.0、2.5、1.0和0毫克/千克/天）和BeWo细胞系（0和50纳摩尔；3小时、12小时和24小时）产生胚胎毒性，从而改变Nrf2/HO-1信号通路的表达。我们的研究结果表明，孕期小鼠接受DON处理会导致胎盘中活性氧（ROS）积累，进而引发胚胎毒性。与此同时，ROS会上调Nrf2/HO-1信号通路，以保护胎盘细胞免受氧化损伤。在经DON处理的BeWo细胞中，ROS水平与HO-1表达存在时间效应和剂量效应关系。适度增加HO-1可保护细胞免受氧化损伤，而过度增加HO-1则会加剧氧化损伤，在一些研究中这被称为“阈值效应”。因此，氧化应激可能是DON诱导胚胎毒性的关键分子机制。此外，伴有“阈值效应”的Nrf2/HO-1信号通路在这一过程中对DON诱导的氧化损伤也起着重要作用。
