Punicalagin prevents cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammatory response, and apoptosis in rats

Abstract

Nephrotoxicity is a major complication that limits the therapeutic application of cisplatin (CIS). Oxidative stress and inflammation are implicated in CIS-induced acute kidney injury (AKI) and apoptotic cell death. Punicalagin (PUN), a polyphenol in pomegranate, possesses promising anti-inflammatory and antioxidant activities, and its beneficial effect against CIS-induced AKI has not been fully elucidated. This investigation evaluated the protective effect of PUN against CIS-induced renal oxidative stress, inflammation and cell death. Rats received PUN (25 and 50 mg/kg) for 10 days and a single injection of CIS at day 7. The results showed increased serum urea and creatinine and several histopathological alterations in the kidney of CIS-intoxicated rats. Renal malondialdehyde (MDA) and nitric oxide (NO) were increased, and reduced glutathione, superoxide dismutase and catalase were declined in rats treated with CIS. PUN effectively ameliorated kidney function and attenuated tissue injury induced by CIS, decreased MDA and NO, and enhanced antioxidant defenses. Additionally, PUN downregulated NF-κB p65, iNOS, TNF-α, IL-6 and IL-1β in the kidney of rats that received CIS. Bax and caspase-3 were increased, and Bcl-2 was decreased in the kidney of CIS-intoxicated rats, an effect that was reversed by PUN. PUN upregulated Nrf2 expression in the kidney of CIS-intoxicated rats. In conclusion, PUN prevents CIS-induced AKI in rats by attenuating oxidative stress, inflammatory response and apoptosis, and upregulating Nrf2 and antioxidants.

Keywords: Chemotherapy; Cisplatin; Inflammation; Nephrotoxicity; Oxidative stress; Punicalagin.