Zingerone mitigates inflammation, apoptosis and oxidative injuries associated with renal impairment in adriamycin-intoxicated mice

Abstract

Adriamycin (ADM), known as doxorubicin, is one of the abundantly consumed and extremely efficient chemotherapeutic agents with subsequent health side effects as nephrotoxicity. Zingerone (ZG) is a phenolic compound present in ginger and possesses many therapeutic effects. The purpose of this study is to test the potential modulatory roles of ZG against ADM mediated nephrotoxicity. Thirty-two male Swiss albino mice were randomly assigned into four groups as follow: Control group (CNT); ZG group, which received an oral dose of 25 mg/kg b.w/day of ZG; ADM group, which are injected with single dose of ADM (25 mg/kg b.w, IV); and ZG/ADM group, this group received dual treatments with the same respective administration routes and doses. After 21 days, serum and kidneys were collected for further examinations. Co-administration of ZG along with ADM significantly lowered serum levels of urea, creatinine, kidney injury molecule-1 and lactate dehydrogenase activity, unlike ADM group. ZG significantly reduced kidney levels of malondialdehyde, nitric oxide and 8-hydroxy-2-deoxyguanosine. Moreover, it retained nuclear factor erythroid 2-related factor 2 mRNA expressions, and glutathione level, as well as catalase and superoxide dismutase activities compared to ADM. Furthermore, ZG permitted the reduction of renal levels for pro-inflammatory cytokines (comprising tumor necrosis factor-α, interleukin-1β, interleukin-6 and nuclear factor kappa B) as well as myeloperoxidase activity, and hence ZG suppresses inflammation induced by ADM. Collectively, our findings indicated that ZG exhibits potential nephroprotective effect toward ADM-mediated nephrotoxicity.