Environmentally relevant levels of Cd and Mo coexposure induces ferroptosis and excess ferritinophagy through AMPK/mTOR axis in duck myocardium.

ABSTRACT

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.