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.