Cadmium (Cd) and excess molybdenum (Mo) are multiorgan toxic, but the detrimental impacts of Cd and/or Mo on poultry have not been fully clarified. Thence, a 16‐week sub‐chronic toxic experiment was executed with ducks to assess the toxicity of Cd and/or Mo. Our data substantiated that Cd and Mo coexposure evidently reduced GSH‐Px, GSH, T‐SOD, and CAT activities and elevated H2O2 and MDA concentrations in myocardium. What is more, the study suggested that Cd and Mo united exposure synergistically elevated Fe2+ content in myocardium and activated AMPK/mTOR axis, then induced ferroptosis by obviously upregulating ACSL4, PTGS2, and TFRC expression levels and downregulating SLC7A11, GPX4, FPN1, FTL1, and FTH1 expression levels. Additionally, Cd and Mo coexposure further caused excessive ferritinophagy by observably increasing autophagosomes, the colocalization of endogenous FTH1 and LC3, ATG5, ATG7, LC3II/LC3I, NCOA4, and FTH1 expression levels. In brief, this study for the first time substantiated that Cd and Mo united exposure synergistically induced ferroptosis and excess ferritinophagy by AMPK/mTOR axis, finally augmenting myocardium injure in ducks, which will offer an additional view on united toxicity between two heavy metals on poultry.

中文翻译：

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环境相关水平的 Cd 和 Mo 共暴露通过 AMPK/mTOR 轴在鸭心肌中诱导铁死亡和过量铁蛋白自噬

镉 (Cd) 和过量的钼 (Mo) 具有多器官毒性，但 Cd 和/或 Mo 对家禽的有害影响尚未完全阐明。因此，用鸭子进行了为期 16 周的亚慢性毒性实验，以评估 Cd 和/或 Mo 的毒性。我们的数据证实，Cd 和 Mo 共暴露明显降低了 GSH-Px、GSH、T-SOD 和 CAT 活性，并且升高的H2氧2和心肌中的 MDA 浓度。更重要的是，研究表明镉和钼联合暴露可协同升高铁2+心肌中含量并激活 AMPK/mTOR 轴，然后通过明显上调 ACSL4、PTGS2 和 TFRC 表达水平并下调 SLC7A11、GPX4、FPN1、FTL1 和 FTH1 表达水平诱导铁死亡。此外，Cd 和 Mo 共暴露通过显着增加自噬体、内源性 FTH1 和 LC3、ATG5、ATG7、LC3II/LC3I、NCOA4 和 FTH1 表达水平的共定位进一步导致过度铁蛋白吞噬。总之，本研究首次证实Cd和Mo联合暴露可协同诱导AMPK/mTOR轴铁死亡和过量铁蛋白自噬，最终加重鸭的心肌损伤，这将为两种重金属对家禽的联合毒性提供新的认识。 。