Hesperidin protects gentamicin-induced nephrotoxicity via Nrf2/HO-1 signaling and inhibits inflammation mediated by NF-κB in rats

• Protective effect of hesperidin (HDN) on nephrotoxicity was studied.
• Reduced expressions of inflammatory mediators were seen during HDN treatment.
• Inversed relationship in the expression of Nrf2 and NF-κB was caused by HDN.
• Multiple mechanisms of action of HDN in restraining nephrotoxicity are suggested.

The defensive effects of hesperidin (HDN, a bioflavonoid) was investigated on gentamicin (GEN) provoked nephrotoxicity in rats. The expression patterns of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), kidney injury molecule (KIM-1), osteopontin, heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS) and heat shock protein-70 (HSP-70) were assessed to comprehend the mechanism of action of hesperidin. GEN treated rats showed increased expressions of KIM-1, osteopontin, COX-2, Nrf2, NF-κB, TNF-α, iNOS, IL-6 and HSP-70 and decreased expression of HO-1. HDN along with GEN decreased the expressions of all indices excluding HO-1 and Nrf2 and an inverse correlation of expression was seen in between Nrf2 and NF-κB. Scavenging of free radicals, suppression of inflammation, upregulation of HO-1 by Nrf2 mediated antioxidant response element system (ARE) and facilitation of antioxidative system by HDN would be responsible to thwart GEN induced renal damage.