α-Tocopherol Ameliorates Redox Equilibrium Disorders and Reduces Inflammatory Response Caused by Diclofenac-Induced Nephrotoxicity in Male Wistar Rats.

Background Diclofenac (DCF), a nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, but it can also be nephrotoxic. Vitamin E (α-tocopherol) has been shown to protect against renal toxicity caused by various agents, including NSAIDs. This study aims to evaluate the pathophysiology of renal damage and the nephroprotective effect of vitamin E against DCF-induced renal damage in male Wistar rats. Animal and methods Twenty-four male Wistar rats, divided into six equal groups, were used for the study. Group 1 (control group) was treated with distilled water only, while the other groups received either high or low doses of DCF with or without a fixed dose of vitamin E. Renal function was assessed by measuring serum urea, creatinine, and kidney injury molecule-1 (KIM-1). Oxidative damage and renal antioxidant levels were also assessed. Additionally, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), renal cytokine tumor necrosis factor-α (TNF-α), and histopathological changes were evaluated. Results DCF caused a significant increase in serum urea, creatinine, KIM-1, TNF-α, NF-κB, and malondialdehyde levels compared to the control group. However, in the groups treated with DCF plus vitamin E, a significant reduction (P<0.05) in the levels of pro-inflammatory cytokines and malondialdehyde was observed, along with improvement in renal function indices, superoxide dismutase, catalase, and glutathione peroxidase levels comparable to the control group. The observed renal histopathological changes were consistent with the results of the biochemical parameters between the treated groups and the normal control rats. Conclusion Findings from this investigation suggested that DCF can be nephrotoxic at a certain dose when used for a prolonged duration. Co-administration of vitamin E suppressed the elevated inflammatory cytokines and led to changes in the cell redox-sensitive signaling pathways induced by DCF, with eventual amelioration of the nephrotoxicity.