Zhang Yongkang, Xu Qiaolin, Sun Qian, Kong Ren, Liu Hao, Yi Xun'e, Liang Zhengqi, Letcher Robert J, Liu Chunsheng
College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
School of Environmental Studies, China University of Geosciences, Wuhan 430074, China.
J Hazard Mater. 2023 Apr 15;448:130791. doi: 10.1016/j.jhazmat.2023.130791. Epub 2023 Jan 13.
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.
最近，我们发现疣孢菌素A（UA，一种霉菌毒素）在来自几个国家的水稻种植环境和大米样本中被广泛检测到，在中国的人类尿液样本中也有发现。然而，目前关于UA健康风险的认识有限。在本研究中，评估了UA对小鼠肾小管上皮细胞（mRTECs）的细胞毒性，结果表明UA通过改变细胞形态和微管使细胞周期停滞在G2/M期，并抑制mRTECs的增殖和分裂。此外，UA可通过与二氢乳清酸脱氢酶（DHODH）蛋白中的辅酶Q结合位点结合来抑制线粒体呼吸，导致线粒体损伤。UA对线粒体的这些不利影响可能是体外观察到的细胞毒性的原因。在体内，与人类实际接触浓度相当的UA浓度会导致小鼠肾功能不全，这可能与小鼠肾线粒体损伤有关。然而，在那些实际浓度下接触UA并没有促进肾功能不全向肾纤维化的进展，并且在小鼠中未观察到慢性肾病。
