Thiophanate-methyl induces severe hepatotoxicity in zebrafish
Thiophanate-methyl induces severe hepatotoxicity in zebrafish
复制标题
甲基托布津会对斑马鱼产生严重的肝毒性。
DOI：
10.1016/j.chemosphere.2020.125941
复制
发表时间：
2020-06-01
期刊：
影响因子：
8.8
通讯作者：
Lu, Huiqiang
中科院分区：
文献类型：
--
作者：
Jia, Kun;Cheng, Bo;Lu, Huiqiang
甲基硫菌灵（TM）在全球广泛使用，是农药残留的典型例子，在土壤甚至蔬菜水果中都能检测到。然而，TM致肝毒性的分子机制尚未完全明晰。在本研究中，我们利用斑马鱼全面评估TM的肝毒性，并探究其诱导肝毒性的分子机制。斑马鱼幼鱼在受精后72至144小时暴露于6.25、12.5和25毫克/升的TM中，而成鱼则在2、4和6毫克/升的TM中暴露28天。我们发现，12.5和25毫克/升的TM会特异性地在斑马鱼幼鱼和成鱼中诱发严重肝毒性，但对其他器官无毒性。此外，它可能通过凋亡途径和氧化应激激活半胱天冬酶 - 3，从而引发斑马鱼的肝毒性。随后，这导致斑马鱼肝脏代谢失衡。总之，我们的研究结果揭示了TM可能通过介导半胱天冬酶 - 3的激活和氧化应激，在斑马鱼中诱导严重肝毒性这一事实。（C）2020爱思唯尔有限公司。保留所有权利。
Thiophanate-methyl (TM) is widely used all over the world and is a typical example of pesticide residues, which can be detected in the soil, and even in vegetables and fruits. However, the molecular mechanisms underlying the hepatotoxicity of TM are not well understood. In this study, we utilized zebrafish to comprehensively evaluate the hepatotoxicity of TM and explore how the molecular mechanisms of hepatotoxicity are induced. The zebrafish larvae were exposed in 6.25, 12.5 and 25 mg/L TM from 72 to 144 hpf, while the adults were exposed in 2, 4 and 6 mg/L TM for 28 days. Here, we found that 12.5 and 25 mg/L TM induces specifically serious hepatotoxicity but not the toxicity of other organs in zebrafish larvae and adults. Moreover, it might triggered hepatotoxicity by activating the caspase-3 through apoptotic pathways and oxidative stress in zebrafish. Subsequently, this resulted in a metabolic imbalance in the zebrafish's liver. In conclusion, our results disclosed the fact that TM may induce severe hepatotoxicity by mediating activation of caspase-3 and oxidative stress in zebrafish. (C) 2020 Elsevier Ltd. All rights reserved.