Punicalagin Opposes Gentamicin Nephrotoxicity in Rats: Role of Nrf2 and NF-κB Pathways

Background: Oxidative stress, inflammation, and apoptosis are implicated in gentamicin (GEN)-induced nephrotoxicity. Punicalagin (PNG) possesses antioxidant, anti-inflammatory, and antiapoptotic effects. Objective: The aim of the present research was to investigate the possible defensive effect of PNG against nephrotoxicity caused by GEN in male Sprague-Dawley rats. Materials and Methods: GEN (80 mg/kg/day, i.p.) was administered for 8 days. Treatment with PNG (25 mg/kg/day, p.o.) for 10 days, began 2 days before GEN insult. Results: PNG significantly decreased serum creatinine, and malondialdehyde, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, nuclear factor-κB p65 (NF- κB p65), and cleaved caspase-3 activity in the kidneys of GEN-challenged rats. PNG also significantly increased renal catalase, reduced glutathione, and nuclear factor erythroid 2-related factor 2 (Nrf2) in rats received GEN. Additionally, PNG markedly attenuated the histopathological kidney tissue injury caused by GEN. Conclusion: PNG guarded against GEN-induced kidney damage in rats through its antioxidant, anti-inflammatory, and antiapoptotic effects, and by modulating the balance between Nrf2 and NF-κB pathways.