Oxidative stress-mediated apoptosis and autophagy involved in Ni-induced nephrotoxicity in the mice

As an extensively environmental pollution, Nickel (Ni) represents a serious hazard to human health. The present study focused on exploring the mechanism of Ni-mediated nephrotoxicity, such as apoptosis, autophagy and oxidative stress. In the current work, NiCl₂ treatment could induce kidney damage. Meanwhile, NiCl₂ treatment elevated ROS production and MDA content and suppressed the antioxidant activity, which was characterized by reducing T-AOC, CAT, SOD activity and GSH content. For investigating the role of oxidative stress on NiCl₂-mediated nephrotoxicity, N-acetyl cysteine (NAC, effective antioxidant and free radical scavenger) was co-treated with NiCl₂. The results showed that NAC significantly suppressed the NiCl₂-mediated oxidative stress and mitigated NiCl₂-induced the kidney damage. Then, whether oxidative stress-induced autophagy and apoptosis were involved in NiCl₂-induced nephrotoxicity was explored. The findings demonstrated that NAC relieved NiCl₂-induced autophagy and reversed the activation of Akt/AMPK/mTOR pathway. Concurrently, the results indicated that NAC attenuated NiCl₂-induced apoptosis, as evidenced by reduction of apoptotic cells and cleaved-caspase-3/- 8/- 9 together with cleaved-PARP protein levels. To sum up, our findings suggested that NiCl₂-mediated renal injury was associated with oxidative stress-induced apoptosis and autophagy. This study provides new theoretical basis for excess Ni exposure nephrotoxic researches.