Oxidative stress and mitochondrial dysfunction involved in ammonia-induced nephrocyte necroptosis in chickens

Ammonia (NH₃), an environmental pollutant, poses a serious threat to human and avian health. Although previous studies have showed that NH₃ caused kidney injury, the molecular mechanisms of nephrotoxicity induced by NH₃ remain unclear. To explore the mechanisms of NH₃ nephrotoxicity, a total of 36 broiler chicks at one day of age were exposed to NH₃. After 42 days of exposure, blood samples were collected to determine creatinine and uric acid; and kidney samples were weighted and then collected to detect ultrastructural changes, oxidative stress parameters, ATPases, necroptosis- and mitochondrial dynamics-related genes. The results showed that chickens exposed to NH₃ showed lower relative kidney weight and an increase concentration in serum creatinine and uric acid. NH₃ exposure caused nephrocyte necrosis and increased the expression of necroptosis-related genes (TNF-α, RIPK1, RIPK3, MLKL, and JNK). Besides, the activities of antioxidant systems (SOD, CAT, GSH-Px, and T-AOC) were reduced, whereas the concentrations of H₂O₂ and MDA were elevated. Lower activities of ATPases were obtained in NH₃ treatment groups. Furthermore, the mitochondrial fission-related genes drp1 and mff were activated, and mitochondrial fusion-related genes opa1, mfn1 and mfn2 were suppressed after NH₃ exposure. Based on the above results, we conclude that NH₃ caused-oxidative stress and mitochondrial dysfunction mediated nephrocyte necroptosis in chickens. This study may provide new insight into NH₃ nephrotoxicity.