Bratislava Medical Journal, 2025 (SCI-Expanded, Scopus)
Diclofenac (DCL) is a nonsteroidal anti-inflammatory drug (NSAID) widely used for the treatment of pain and inflammation. However, its extensive use has raised concerns due to its nephrotoxic effects, primarily mediated by oxidative stress, inflammation, and programmed cell death pathways. Zingerone (ZNG), a natural phenolic compound derived from ginger, has demonstrated significant antioxidant and anti-inflammatory properties in various experimental models. This study aimed to investigate the potential protective effects of ZNG against DCL-induced nephrotoxicity in rats. Thirty-five male Wistar albino rats were randomly assigned to five groups: control, ZNG alone, DCL alone, DCL + low-dose ZNG (25 mg/kg), and DCL + high-dose ZNG (50 mg/kg). DCL administration induced significant kidney injury, evidenced by elevated serum urea and creatinine, increased oxidative stress markers (MDA, 8-OHdG), suppressed antioxidant defenses (SOD, CAT, GPx, GSH), histopathological damage, and dysregulation of pro-inflammatory, apoptotic, and autophagic genes, alongside reduced anti-apoptotic and survival-related gene expression. Co-treatment with ZNG, particularly at 50 mg/kg, markedly mitigated these biochemical, histological, and molecular alterations. These findings demonstrate that ZNG exerts nephroprotective effects by enhancing antioxidant defenses, reducing inflammation and cell death, and modulating key cellular pathways.