Propolis ameliorates cisplatin-induced nephrotoxicity via activation of Nrf2/HO-1 signaling pathway in rats

Cisplatin is among the most widely used chemotherapeutic drugs for the treatment of solid tumors; nonetheless, nephrotoxicity persists as a significant dose-limiting adverse effect. The current study focuses on the protective effect of propolis against cisplatin-induced kidney damage in experimental rats. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin at a dose of 5 mg/kg, ip, followed by propolis oral administration. The chemical profile of the propolis extract was characterized using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Biochemical parameters of renal function (urea and creatinine), oxidative stress markers (MDA, SOD, CAT and GSH), proinflammatory markers (IL-6, TNF-α and IL-1ꞵ) and RT-PCR were performed along with histopathological and immunohistochemical investigations. LC-MS analysis revealed that the propolis contained several bioactive phenolic acids and flavonoids, with pyrocatechol, iso-ferulic acid, gallic acid, apigenin, kaempferol, quercetin, which may contribute to the antioxidant and nephroprotective effects of propolis. The results demonstrated that cisplatin markedly increased serum levels of urea and creatinine and elevated lipid peroxidation and inflammation, accompanied by notable damage in renal structure. Conversely, propolis treatment significantly ameliorated these adverse effects by restoring antioxidant status, reducing oxidative stress and improving histological structure. Furthermore, administration of propolis significantly suppressed inflammation by reducing proinflammatory cytokines levels and the expression of caspase-3. In addition, immunohistochemical results revealed that propolis treatment markedly increased Nrf2/HO-1 expression in kidney tissue. In conclusion, these findings suggested that propolis exerts nephroprotective effects against cisplatin-induced nephrotoxicity via its anti-inflammatory and antioxidant activities.