College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Laboratory Animal Centre, Qiqihar Medical University, Qiqihar, 161006, PR China.
Chemosphere. 2018 Dec;212:974-982. doi: 10.1016/j.chemosphere.2018.08.138. Epub 2018 Aug 30.
Atrazine (ATR) is a most used herbicide which is believed as a pivotal determinant of environmental nephrosis, but potential mechanism is still largely unclear. This study intends to reveal a novel mechanism of ATR-induced nephrotoxicity. Quail were treated with 0, 50, 250 and 500 mg ATR/kg/d by oral gavage for 45 days. Kidney coefficient was decreased, biochemical and morphologic indices reflecting the kidney injury were significantly increased in ATR-exposed quail. ATR exposure upregulated the expression of proapoptotic factors (Bax, Caspase 3 and FasL) and downregulated antiapoptotic factor (Bcl-2). Notably, cristae of mitochondria decreased, mitochondrial malformation and mitochondrial vacuolar degeneration were observed in ATR-exposed quail. ATR induced the disorder of mitochondrial function related factors expressions and promoted oxidative damage. Furthermore, ATR induced toxicities in the expression of Nrf2 and Nrf2-target genes. In conclusion, ATR altered the microstructure and function of quail kidney. ATR induced renal damage via causing mitochondrial dysfunction, influencing mitochondrial function related genes expression, modulating Nrf2 signaling pathway. This study suggested ATR induced the nephrotoxicity via disturbing the transcription of mitochondrial function related factors and Nrf2 signaling pathway.
莠去津（ATR）是一种应用最广泛的除草剂，被认为是环境性肾病的关键决定因素，但潜在的机制仍很大程度上不清楚。本研究旨在揭示 ATR 诱导肾毒性的新机制。鹌鹑通过口服灌胃用 0、50、250 和 500mgATR/kg/d 处理 45 天。ATR 暴露组鹌鹑的肾脏系数降低，反映肾脏损伤的生化和形态学指标显著增加。ATR 暴露上调了促凋亡因子（Bax、Caspase 3 和 FasL）的表达，下调了抗凋亡因子（Bcl-2）的表达。值得注意的是，在 ATR 暴露的鹌鹑中观察到线粒体嵴减少、线粒体畸形和线粒体空泡变性。ATR 诱导与线粒体功能相关的因子表达紊乱，促进氧化损伤。此外，ATR 诱导 Nrf2 和 Nrf2 靶基因的毒性表达。总之，ATR 改变了鹌鹑肾脏的微观结构和功能。ATR 通过引起线粒体功能障碍、影响线粒体功能相关基因表达、调节 Nrf2 信号通路导致肾损伤。本研究表明，ATR 通过干扰线粒体功能相关因子和 Nrf2 信号通路的转录导致肾毒性。
