Astaxanthin attenuates doxorubicin-induced liver injury via suppression of ferroptosis in rats

• The needs of hepatotoxicity-reduction strategy of doxorubicin (DOX) is urgent. • The effect of astaxanthin on DOX-induced hepatotoxicity is unclear. • Astaxanthin can prevent adverse effect of DOX exposure in rat liver and HepG2 cells. • Astaxanthin may prevent DOX-induced hepatotoxicity by inhibiting ferroptosis. Hepatotoxicity is an significant side effect of doxorubicin (DOX), while astaxanthin (ASX) has the anti-liver injury biological functions. In this study, we utilized in vivo and in vitro methods to investigate the protective effect of ASX against DOX-induced hepatotoxicity and elucidate its potential mechanism. Our researchers measured liver injury indicators and the expression of ferroptosis-related protein (transferrin receptor 1 (TFRC), ferroportin 1 (FPN1), ferritin light chain (FTL), ferritin heavy chain-1 (FTH1), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11)) in rats and HepG2 cells. We found that ASX could effectively reduce ferroptosis level and relieve a range of DOX-caused manifestations of liver injury, including inflammation and oxidative damage. ASX may play the same role as ferroptosis inhibitor, Fer-1 and DFP, in this process. The findings demonstrated that the intervention with ASX ameliorated the DOX-induced liver injury by mitigating the DOX-induced ferroptosis through inhibiting iron accumulation.