Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, 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.
Sci Total Environ. 2021 Mar 10;759:143570. doi: 10.1016/j.scitotenv.2020.143570. Epub 2020 Nov 11.
Cadmium (Cd) and excessive molybdenum (Mo) are detrimental to animals, but the combined nephrotoxic impacts of Cd and Mo on duck are still unclear. To evaluate the combined impacts of Cd and Mo on autophagy via Cytochrome P450s (CYP450s)/reactive oxygen species (ROS) pathway, duck renal tubular epithelial cells were treated with 3CdSO·8HO (4.0 μM Cd), (NH)MoO·4HO (500.0 μM Mo), butylated hydroxy anisole (BHA) (100.0 μM) and combination of Cd and Mo or Cd, Mo and BHA for 12 h, and combined cytotoxicity was investigated. The results indicated that Mo or/and Cd induced CYP1A1, CYP1B1, CYP2C9, CYP3A8 and CYP4B1 mRNA levels, decreased superoxide dismutase (SOD), catalase (CAT) activities and glutathione peroxidase (GSH-Px) content, and increased malondialdehyde (MDA) and hydrogen peroxide (HO) contents. Besides, Mo or/and Cd elevated the number of autophagosome and microtubule-associated protein light chain 3 (LC3) puncta, upregulated mRNA levels of Beclin-1, LC3A, LC3B, Atg5 and adenosine 5'-monophosphate (AMP)-activated protein kinase α1 (AMPKα-1), inhibited Dynein, p62 and mammalian target of rapamycin (mTOR) mRNA levels, increased Beclin-1 and LC3II/LC3I protein levels. Moreover, the changes of these factors in Mo and Cd co-treated groups were more apparent. Additionally, BHA could efficiently alleviate the changes of above these indicators co-induced by Mo and Cd. Overall, these results manifest Cd and Mo co-exposure may synergistically trigger autophagy via CYP450s/ROS pathway in duck renal tubular epithelial cells.
镉（Cd）和过量的钼（Mo）对动物有害，但 Cd 和 Mo 联合对鸭的肾毒性影响尚不清楚。为了评估细胞色素 P450s（CYP450s）/活性氧（ROS）途径通过自噬对 Cd 和 Mo 的联合影响，用 3CdSO·8HO（4.0μM Cd）、（NH）MoO·4HO（500.0μM Mo）、丁基化羟基茴香醚（BHA）（100.0μM）和 Cd 和 Mo 或 Cd、Mo 和 BHA 联合处理鸭肾小管上皮细胞 12 小时，研究了联合细胞毒性。结果表明，Mo 或/和 Cd 诱导 CYP1A1、CYP1B1、CYP2C9、CYP3A8 和 CYP4B1mRNA 水平，降低超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性和谷胱甘肽过氧化物酶（GSH-Px）含量，增加丙二醛（MDA）和过氧化氢（HO）含量。此外，Mo 或/和 Cd 增加自噬体和微管相关蛋白轻链 3（LC3）斑点的数量，上调 Beclin-1、LC3A、LC3B、Atg5 和腺苷 5'-单磷酸（AMP）激活的蛋白激酶α1（AMPKα-1）mRNA 水平，抑制动力蛋白、p62 和雷帕霉素靶蛋白（mTOR）mRNA 水平，增加 Beclin-1 和 LC3II/LC3I 蛋白水平。此外，Mo 和 Cd 共同处理组中这些因素的变化更为明显。此外，BHA 可有效缓解 Mo 和 Cd 共同诱导的上述指标的变化。综上所述，这些结果表明 Cd 和 Mo 共同暴露可能通过 CYP450s/ROS 途径协同触发鸭肾小管上皮细胞自噬。
