Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Comp Biochem Physiol C Toxicol Pharmacol. 2020 Jul;233:108771. doi: 10.1016/j.cbpc.2020.108771. Epub 2020 Apr 23.
Thiocarbamates are one of the components of pesticides that target weeds by inhibiting adenosine triphosphate (ATP) synthesis. Orbencarb, one of the isomeric thiocarbamates applied to wheat, maize, and soybean, has been found to have toxic effects on mammals and marine ecosystems. Although the toxicity ranges of orbencarb in different organisms are known, specific studies on the environmental contamination and harmful effects of orbencarb on non-target organisms are scarce. In this study, we observed that orbencarb induced embryotoxicity during zebrafish development as well as apoptosis and reactive oxygen species (ROS) production in the intestine. It was further observed that orbencarb decreased the viability of the embryos and simultaneously affected the heart rate and vessel formation. Orbencarb decreased the mRNA levels of ccnd1, ccne1, cdk2, and cdk6 and induced abnormal development of the eyes, brain, yolk sac, and spinal cord in zebrafish embryos. Orbencarb also hampered vasculogenesis in the zebrafish embryos by inhibiting the mRNA expression of flt1, flt4, kdr, and vegfc. Collectively, these results suggested that orbencarb is embryotoxic and disrupts the normal growth of zebrafish embryos by inducing the generation of ROS and hampering vasculogenesis.
硫代氨基甲酸盐是通过抑制三磷酸腺苷（ATP）合成来靶向杂草的农药成分之一。作为应用于小麦、玉米和大豆的硫代氨基甲酸盐异构体之一的涕灭威砜，已被发现对哺乳动物和海洋生态系统具有毒性作用。尽管已知涕灭威砜在不同生物体中的毒性范围，但对其在非靶标生物中的环境污染和有害影响的具体研究却很少。在这项研究中，我们观察到涕灭威砜在斑马鱼发育过程中诱导胚胎毒性，以及在肠道中诱导细胞凋亡和活性氧（ROS）产生。进一步观察到涕灭威砜降低了胚胎的存活率，同时影响了心率和血管形成。涕灭威砜降低了 ccnd1、ccne1、cdk2 和 cdk6 的 mRNA 水平，并诱导了斑马鱼胚胎的眼睛、大脑、卵黄囊和脊髓的异常发育。涕灭威砜还通过抑制 flt1、flt4、kdr 和 vegfc 的 mRNA 表达，阻碍了斑马鱼胚胎的血管生成。总之，这些结果表明涕灭威砜具有胚胎毒性，通过诱导 ROS 的产生和阻碍血管生成，扰乱了斑马鱼胚胎的正常生长。
