LAUSR

Acute alcoholism commonly targets the myocardium, triggering acute alcoholic cardiomyopathy (ACM). Strong evidence suggested that mitochondrial dysfunction‐induced myocardial oxidative stress is involved in the subcellular pathogenesis of acute ACM. We investigated whether astaxanthin (AST), an antioxidant lutein carotenoid, prevents acute ACM and explored the underlying mechanisms. C57BL/6J mice were used to model ethanol‐induced ACM and were treated with AST (100 mg/kg/day) alongside the autophagy inhibitor, 3‐methyladenine (10 mg/kg/day). Cardiac function, heart pathology, cardiac hypertrophy, cardiomyocyte apoptosis, oxidative stress and mitochondrial function were evaluated, respectively in response to ethanol and/or AST. The in vivo study showed that ethanol‐induced cardiac dysfunction, morphological injury, cardiomyocyte apoptosis and oxidative stress were mitigated by AST. AST's anti‐apoptotic effects against ethanol were confirmed in vitro. Ethanol‐induced cardiac apoptosis is closely associated with mitochondrial dysfunction which was attenuated by AST characterised by inhibiting fission and promoting fusion, as well as maintaining stable mitochondrial membrane potential, increased ATP production, enhanced biogenesis and restored mitophagy. Autophagy inhibition suppressed AST‐induced myocardial protection, indicating that myocardial mitophagy mediates AST effects. The present study demonstrates that AST induces cardiac protection against acute ACM by improving cardiac function, reducing pathological changes, and inhibiting oxidative stress, inflammation and apoptosis through preserved myocardial mitophagy‐mediated mitochondrial homeostasis.