Destruction of redox and mitochondrial dynamics co-contributes to programmed cell death in chicken kidney under arsenite or/and copper (II) exposure

Background Sub-chronic arsenic (arsenite) exposure-induced oxidative toxicity leads to adverse effects in various organ systems, especially the kidney. Copper sulphate (Cu2+), known for its extensive uses in agriculture, has also been reported to have pro-oxidation properties. Both of these two potential toxic elements can bio-accumulate through food chain, thus endangering human health. However, their interaction study in the kidney is scanty. Aim: To investigate the synergism effects of Cu2+ in arseniasis-elicited oxidative stress and cascaded renal injury in chickens. Results: Arsenite intoxication decreased renal antioxidant system along with ATPases. Arsenite exposure also significantly elicited disequilibrium of mitochondrial homeostasis, accompanying by elevated apoptotic and autophagic cell death. The disturbed morphological and ultrastructural changes further corroborated arsenite nephrotoxicity. These anomalies aligned with the findings in Cu2+ groups, which co-administrated with arsenic further deteriorated these pathological changes. This synergism was achieved partially via the inactivation of phosphoinositide-3-kinase/protein kinase b/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway through the activation of P53. Conclusions: Copper excess and arsenic exposure can function independently or cooperatively to affect oxidative stress, mitochondrial dynamics and programmed cell death. These results highlighted the need to take precautions against copper and arsenic co-exposure when considering their impact in susceptible animals/populations.