The Protective Effects of Methionine on Nickel-Induced Oxidative Stress via NF-κB Pathway in the Kidneys of Mice

Nickel (Ni) is a human carcinogen that causes oxidative damage to many organs, and methionine has been studied to protect mammals from similar toxic effects by other heavy metals possibly through sulfur metabolism. This study aimed to investigate the protective effects of methionine on Ni-induced injuries to the kidneys. In this study, the mice were randomly divided into BC (normal diet), MD (methionine deficiency diet), MN (methionine plus nickel diet), and MDN (methionine deficiency plus nickel diet) treatment groups. Their renal function, histological changes, cell cycle, apoptosis, oxidative damage, and NF-κB inflammatory cytokines were detected after 21 days by HE, immunohistochemistry, TUNEL staining, and biochemical and ELISA methods. The results showed that serum Cr, BUN, and the NAG content increased in MDN (P < 0.01), MN (P < 0.05), and MD (P < 0.05) group mice compared to BC group mice. Glomerulus atrophy and renal tubular atrophy were observed in the MDN, MN, and MD groups but less severe in MN group mice. The PCNA protein content was the highest in BC group mice followed by MD, MN, and MDN. The activities of antioxidant enzymes (SOD, CAT, GSH, GSH-Px, and GSH-ST) were lower significantly in MD, MN, and MDN group mice, and the oxidant products content (MDA, LPO, and ROS) in the BC group were higher than those in other groups with a similar trend. The contents of NF-κB, TNF-α, IFN-γ, IL-1a, and IL-6 in the BC group were found to increase significantly in MD, MN, and MDN groups. In conclusion, Ni-induced kidney injury was indicated by renal tissue and cell damage, increased kidney metabolism products release in the serum, and renal oxidative stress while methionine addition helped alleviate the injury. In addition, the NF-κB signal pathway was involved in the renal inflammatory reaction induced by Ni where methionine helped mitigate it.