Cardiac PTN-SIRT1 axis alleviates oxidative stress and promotes mitochondrial energy reprogramming to mitigate doxorubicin-induced cardiotoxicity through AMPK/PGC1α signaling

• DOX-induced cardiotoxicity is associated with downregulation of PTN in cardiomyocytes, leading to mitochondrial dysfunction and oxidative stress. • Overexpression of PTN alleviates DIC by reducing oxidative stress, apoptosis, and restoring mitochondrial energy production in vitro and in vivo. • PTN directly binds to SIRT1, activating AMPK phosphorylation at Thr172 and the downstream AMPK-PGC1α pathway, which reprograms mitochondrial energy metabolism. • The PTN-SIRT1 axis represents a novel therapeutic target for preventing chemotherapy-related cardiac injury.