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

• Published in: The Science of the total environment Vol. 689; pp. 1160 - 1171
• Main Authors: Ge, Jing, Zhang, Cong, Sun, Yan-Chun, Zhang, Qi, Lv, Mei-Wei, Guo, Kai, Li, Jin-Long
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2019
• Subjects: Cadmium; Mitochondrial dynamic homeostasis; Mitochondrial unfolded protein response; Nephrotoxicity; Nrf2 antioxidant defense; Cadmium; Nrf2 antioxidant defense; Nephrotoxicity; Mitochondrial unfolded protein response; Mitochondrial dynamic homeostasis
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2019.06.405

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. Cadmium (Cd) is a widespread environmental pollutant that accumulates in living systems and exerts significant global health hazards. Cd enters the kidney through cell membranes and disrupts the metabolic system, ultimately resulting in nephrotoxicity. Our findings provide new evidence that Cd exposure affects the regulation of the UPRmt and the Nrf2-mediated antioxidant response in the kidney. [Display omitted] •Cadmium exposure caused nephrotoxicity.•Cadmium disturbed the homeostasis of trace elements in kidney.•Cadmium induced oxidative stress via affecting Nrf2 mediated antioxidant defense.•Cadmium induced mitochondrial injury via inhibition of mitochondrial UPR.