Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045, Jiangxi, PR China.
School of Information Technology,Jiangxi University of Finance and Economics, No. 665 Yuping West Street, Economic and Technological Development District, Nanchang, 330032, Jiangxi, PR China.
Environ Pollut. 2021 Mar 1;272:116403. doi: 10.1016/j.envpol.2020.116403. Epub 2020 Dec 30.
Cadmium (Cd) and excess molybdenum (Mo) are harmful to animals, but the combined nephrotoxic mechanism of Cd and Mo in duck remains poorly elucidated. To assess joint effects of Cd and Mo on pyroptosis via ROS/PTEN/PI3K/AKT axis in duck renal tubular epithelial cells, cells were cultured with 3CdSO·8HO (4.0 μM), (NH)MoO·4HO (500.0 μM), MCC950 (10.0 μM), BHA (100.0 μM) and combination of Cd and Mo or Cd, Mo and MCC950 or Cd, Mo and BHA for 12 h, and the joint cytotoxicity was explored. The results manifested that toxicity of non-equitoxic binary mixtures of Mo and Cd exhibited synergic interaction. Mo or/and Cd elevated ROS level, PTEN mRNA and protein levels, and decreased PI3K, AKT and p-AKT expression levels. Simultaneously, Mo or/and Cd upregulated ASC, NLRP3, NEK7, Caspase-1, GSDMA, GSDME, IL-18 and IL-1β mRNA levels and Caspase-1 p20, NLRP3, ASC, GSDMD protein levels, increased the percentage of pyroptotic cells, LDH, NO, IL-18 and IL-1β releases as well as relative conductivity. Moreover, NLRP3 inhibitor MCC950 and ROS scavenger BHA could ameliorate the above changed factors induced by Mo and Cd co-exposure. Collectively, our results reveal that combination of Mo and Cd synergistically cause oxidative stress and trigger pyroptosis via ROS/PTEN/PI3K/AKT axis in duck tubular epithelial cells.
镉 (Cd) 和过量钼 (Mo) 对动物有害，但 Cd 和 Mo 联合对鸭肾脏的肾毒性机制仍不清楚。为了评估 ROS/PTEN/PI3K/AKT 轴在鸭肾小管上皮细胞中 Cd 和 Mo 对细胞焦亡的联合作用，用 3CdSO·8HO（4.0μM）、(NH)MoO·4HO（500.0μM）、MCC950（10.0μM）、BHA（100.0μM）和 Cd 和 Mo 的混合物或 Cd、Mo 和 MCC950 的混合物或 Cd、Mo 和 BHA 处理细胞 12 小时，探讨了联合细胞毒性。结果表明，Mo 和 Cd 的非等毒性二元混合物的毒性表现出协同作用。Mo 或/和 Cd 增加了 ROS 水平、PTEN mRNA 和蛋白水平，降低了 PI3K、AKT 和 p-AKT 表达水平。同时，Mo 或/和 Cd 上调了 ASC、NLRP3、NEK7、Caspase-1、GSDMA、GSDME、IL-18 和 IL-1β mRNA 水平和 Caspase-1 p20、NLRP3、ASC、GSDMD 蛋白水平，增加了细胞焦亡、LDH、NO、IL-18 和 IL-1β 释放以及相对电导率的百分比。此外，NLRP3 抑制剂 MCC950 和 ROS 清除剂 BHA 可以改善 Mo 和 Cd 共暴露引起的上述变化。综上所述，我们的研究结果表明，Mo 和 Cd 的联合作用通过 ROS/PTEN/PI3K/AKT 轴协同引起鸭肾小管上皮细胞氧化应激，并引发细胞焦亡。
