Embryotoxicity Caused by DON-Induced Oxidative Stress Mediated by Nrf2/HO-1 Pathway
AbstractDeoxynivalenol (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. View Full-Text
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Yu, M.; Chen, L.; Peng, Z.; Wang, D.; Song, Y.; Wang, H.; Yao, P.; Yan, H.; Nüssler, A.K.; Liu, L.; Yang, W. Embryotoxicity Caused by DON-Induced Oxidative Stress Mediated by Nrf2/HO-1 Pathway. Toxins 2017, 9, 188.
Yu M, Chen L, Peng Z, Wang D, Song Y, Wang H, Yao P, Yan H, Nüssler AK, Liu L, Yang W. Embryotoxicity Caused by DON-Induced Oxidative Stress Mediated by Nrf2/HO-1 Pathway. Toxins. 2017; 9(6):188.Chicago/Turabian Style
Yu, Miao; Chen, Liangkai; Peng, Zhao; Wang, Di; Song, Yadong; Wang, Hanyin; Yao, Ping; Yan, Hong; Nüssler, Andreas K.; Liu, Liegang; Yang, Wei. 2017. "Embryotoxicity Caused by DON-Induced Oxidative Stress Mediated by Nrf2/HO-1 Pathway." Toxins 9, no. 6: 188.
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