Astaxanthin mitigates cardiac toxicity induced via doxorubicin by alleviating mitochondrial fission and autophagy in rats.

Doxorubicin (DOX)-induced cardiotoxicity is the most prevalent adverse reaction of DOX during chemotherapy and significantly impacts its clinical application. At present, clinical interventions for mitigating DOX-induced cardiotoxicity remain sub-optimal. Mitochondria are the primary target organ of DOX-induced cardiotoxicity, which can result in cardiac mitochondrial dynamic imbalance and impaired mitochondrial autophagy. Astaxanthin (ASTA) is an antioxidant that exerts cardioprotective effects in various cardiac diseases. Meanwhile, it can also ameliorate mitochondrial dynamic dysregulation and suppress the abnormal activation of autophagy. Therefore, ASTA was administered to a rat model of DOX-induced cardiotoxicity, and its cardioprotective effects were observed. Additionally, the mechanisms underlying its cardioprotective effects were investigated by detecting proteins related to mitochondrial dynamics and mitophagy. The results revealed that ASTA up-regulated the expression of mitochondrial fusion protein 2(Mfn2) and Optic Atrophy 1(OPA1), reduced the expression level of dynamin-related protein 1 (Drp1) and Fission 1 Protein(Fis-1), and regulated PTEN-Induced Putative Kinase 1(PINK1)/ Parkin RBR E3 Ubiquitin Protein Ligase (Parkin)-mediated mitochondrial autophagy to alleviate mitochondrial damage in the rat model. Consequently, we hypothesize that ASTA alleviates DOX-induced cardiotoxicity by regulating mitochondrial dynamic imbalance and mitophagy, thereby attenuating mitochondrial damage and exerting cardioprotective effects. Overall, these findings indicate that ASTA holds promise as a prospective drug for ameliorating DOX-induced cardiotoxicity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-17253-1.