线粒体
体外
细胞毒性
体内
肾
生物
细胞凋亡
药理学
化学
生物化学
内分泌学
生物技术
作者
Yongkang Zhang,Qiaolin Xu,Qian Sun,Ren Kong,Hao Líu,Xun’e Yi,Zhengqi Liang,Robert J. Letcher,Chunsheng Liu
标识
DOI:10.1016/j.jhazmat.2023.130791
摘要
Recently, we found that Ustiloxin A (UA, a mycotoxin) was widely detected in paddy environment and rice samples from several countries, and was also detected in human urine samples from China. However, the current knowledge about the health risks of UA are limited. In this research, the cytotoxicity of UA in mice renal tubular epithelial cells (mRTECs) was evaluated, and the results indicated that UA arrested cell cycle in G2/M phase via altering cellular morphology and microtubule, and inhibited the proliferation and division of mRTECs. Furthermore, UA could inhibit mitochondrial respiration via binding to the CoQ-binding site in dihydro-orotate dehydrogenase (DHODH) protein, and resulted in mitochondrial damage. These adverse effects of UA on mitochondria might be responsible for the cytotoxicity observed in vitro. In vivo, UA at concentrations that were comparable to the realistic concentrations of human exposure induced renal insufficiency in mice, and this might be associated with the renal mitochondrial damage in mice. However, exposure to UA at those realistic concentrations did not promote the progression from renal insufficiency to renal fibrosis and chronic kidney disease was not observed in mice.
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