Paeonol alleviates epirubicin-induced renal injury in mice by regulating Nrf2 and NF-κB pathways

Abstract

Renal injury is a dose-dependent side effect of epirubicin that limits its clinical application in the field of tumor chemotherapy. Paeonol is an active ingredient with a variety of biological activities, including the prevention of multiple antineoplastic-induced toxicities. In the present study, we assessed the renoprotective effect of paeonol on epirubicin-induced nephrotoxicity and investigated the underlying mechanism. Renal function, kidney histology, oxidative stress, nitrative stress, inflammation, apoptotic proteins and the effects on signaling pathways were investigated. Paeonol lowered the levels of biomarkers of renal injury, relieved histopathological alterations, alleviated oxidative stress and nitrative stress, and ameliorated inflammation. Moreover, paeonol inhibited epirubicin-induced apoptosis by suppressing the activation of caspase-9 and caspase-3, the Bax/Bcl-2 imbalance and cytochrome c release. Further studies suggest that paeonol up-regulates the Nrf2/HO-1 pathway by increasing the expression of Nrf2 and HO-1 and down-regulates the NF-κB pathway by reducing IκBα degradation and blocking the p-NF-κB nuclear translocation. In conclusion, paeonol alleviates epirubicin-induced renal injury in mice by regulating the Nrf2 and NF-κB signaling pathways.