P2Y12-AMPKα2 signaling contributes to cardiomyocyte senescence in doxorubicin-induced heart failure

Doxorubicin (DOX)-induced cardiotoxicity is closely associated with oxidative stress, DNA damage, and senescence-related cardiac injury. This study evaluated the protective effects of Floralozone against DOX-induced cardiac injury and explored the associated molecular changes. Floralozone alleviated DOX-induced cardiac dysfunction, myocardial structural damage, oxidative stress, DNA damage responses, and senescence-related changes in vivo and in vitro. These protective effects were accompanied by modulation of the P2Y12-AMPKα2-ASK1-MEK3-related stress signaling axis. These findings suggest that Floralozone may protect against DOX-induced cardiac injury by suppressing oxidative stress, attenuating DNA damage responses, and reducing senescence-related signaling.