Galangin attenuates doxorubicin‐induced cardiotoxicity via activating nuclear factor erythroid 2‐related factor 2/heme oxygenase 1 signaling pathway to suppress oxidative stress and inflammation

Abstract

AbstractDoxorubicin (DOX) has aroused contradiction between its potent anti‐tumor capacity and severe cardiotoxicity. Galangin (Gal) possesses antioxidant, anti‐inflammatory, and antiapoptotic activities. We aimed to explore the role and underlying mechanisms of Gal on DOX‐induced cardiotoxicity. Mice were intraperitoneally injected with DOX (3 mg/kg, every 2 days for 2 weeks) to generate cardiotoxicity model and Gal (15 mg/kg, 2 weeks) was co‐administered via gavage daily. Nuclear factor erythroid 2‐related factor 2 (Nrf2) specific inhibitor, ML385, was employed to explore the underlying mechanisms. Compared to DOX‐insulted mice, Gal effectively improved cardiac dysfunction and ameliorated myocardial damage. DOX‐induced increase of reactive oxygen species, malondialdehyde, and NADPH oxidase activity and downregulation of superoxide dismutase (SOD) activity were blunted by Gal. Gal also markedly blocked increase of IL‐1β, IL‐6, and TNF‐α in DOX‐insulted heart. Mechanistically, Gal reversed DOX‐induced downregulation of Nrf2, HO‐1, and promoted nuclear translocation of Nrf2. ML385 markedly blunted the cardioprotective effects of Gal, as well as inhibitive effects on oxidative stress and inflammation. Gal ameliorates DOX‐induced cardiotoxicity by suppressing oxidative stress and inflammation via activating Nrf2/HO‐1 signaling pathway. Gal may serve as a promising cardioprotective agent for DOX‐induced cardiotoxicity.