Cadmium exposure triggers mitochondrial dysfunction and oxidative stress in chicken (Gallus gallus) kidney via mitochondrial UPR inhibition and Nrf2-mediated antioxidant defense activation.

Cadmium (Cd) is a widespread environmental pollutant that accumulates in living systems and represents a significant global health hazard. Cd poses a toxicity threat to both human and animal health, including that of birds. Further knowledge of Cd toxicology pathways will allow for a better understanding of Cd-induced nephrotoxicity. To evaluate Cd-induced nephrotoxicity through potential oxidative damage, male chickens were treated with 0 mg/kg, 35 mg/kg or 70 mg/kg CdCl2 in diet for 90 days. Markedly, histopathology indicated renal tubular epithelial cell swelling, renal function CREA content abnormalities, biochemical and morphologic indices indicative of Cd-induced kidney injury. Cd toxicity induced the up-regulation of Nrf2 and downstream target genes that relieve oxidative stress. Meanwhile, Cd disrupted the homeostasis of trace elements and promoted oxidative damage. Cd interfered with mitochondrial unfolded protein response (UPRmt)-related factors (SIRT1, SIRT3, PGC-1α, TFAM, Nrf1, and HTRA2) and disrupted the homeostasis of mitochondrial dynamics (OPA1, MFN1, MFN2, Fis1 and MFF), thereby exacerbating mitochondrial structural damage and mitochondrial dysfunction. In conclusion, our study demonstrated that the nephrotoxicity of Cd exposure results in oxidative stress and mitochondrial dysfunction by activating the Nrf2 signaling pathway and inhibiting UPRmt in the kidneys.