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

Doxorubicin (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.

Galangin; Nrf2/HO-1 signaling pathway; cardiomyocyte apoptosis; doxorubicin-induced cardiotoxicity; inflammation; oxidative stress.