Astaxanthin alleviates dibutyl phthalate-induced cardiotoxicity in zebrafish larvae by regulating mitophagy

Dibutyl phthalate (DBP), an environmental endocrine disruptor, has been shown to pose potential risks for inducing cardiotoxicity, although its precise mechanism remains incompletely understood, and effective preventive strategies are lacking. Astaxanthin (AST), known for its potent antioxidant properties and potential cardiovascular protective effects, has garnered widespread attention. This study demonstrates that environmental concentrations of DBP cause cardiac dysfunction in zebrafish and reduce viability while increasing apoptosis in human cardiomyocytes (AC16), accompanied by elevated cardiac injury markers. Mechanistically, DBP induces mitochondrial oxidative stress (including increased ROS production, impaired antioxidant systems, and mitochondrial membrane potential and function disruption), leading to activation of the PINK1/Parkin pathway and excessive mitophagy. Intervention with AST alleviates oxidative stress, enhances mitochondrial function, and normalizes the overactivated mitophagy. Both in animal and cell models, AST exhibits significant cardioprotective effects. This study is the first to reveal that AST mitigates DBP-induced cardiotoxicity by regulating mitochondrial autophagy homeostasis, providing new insights into the molecular mechanisms of environmental pollutants-induced cardiovascular injury and potential therapeutic strategies.