Southeast University, Nanjing 211189, China; College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China; Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
Environ Toxicol Pharmacol. 2022 Oct;95:103973. doi: 10.1016/j.etap.2022.103973. Epub 2022 Sep 9.
Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.
赭曲霉毒素 A（OTA）是一种主要引起肾毒性的真菌毒素。OTA 对肾小球或肾小管的单一肾毒性已有充分的文献记载，但两者之间的比较毒性仍不清楚。本研究采用浓度梯度 OTA 处理 C57BL/6 小鼠和两种肾细胞，以探讨其分化肾毒性。结果表明，OTA 在体内和体外均诱导肾毒性，表现为小鼠肾功能恶化和肾细胞活力下降。此外，两种肾细胞的小鼠肾脏病理切片和 IC 结果表明，OTA 诱导的肾小管毒性高于肾小球。此外，OTA 暴露诱导自噬信号的分化表达。结果表明，自噬参与了 OTA 诱导的肾小球和肾小管的差异肾毒性。总之，我们证明了 OTA 诱导肾小球和肾小管的分化肾毒性，这与自噬的差异调节有关。
