Spermine alleviates myocardial cell aging by inhibiting mitochondrial oxidative stress damage

Myocardial aging, involving oxidative stress, mitochondrial dysfunction, and cellular senescence, is crucial to DOX - induced heart failure. DOX has dose - dependent cardiotoxicity. Sper a natural polyamine with antioxidant and anti - aging effects, remains unstudied in this context.

This study hypothesizes Sper can alleviate DOX - induced heart failure by curbing myocardial aging and oxidative stress. It aims to assess Sper's protective impacts on cardiac function, pathology, oxidative stress, mitochondrial damage, and aging in a rat model, using captopril as a control.

80 male Sprague Dawley rats were assigned to 8 groups: normal control, 150 mg/kg Sper, DOX, and DOX +10/50/100/150 mg/kg Sper, DOX +30 mg/kg captopril. DOX was given intraperitoneally at 15 mg/kg total dose, while Sper or captopril was administered daily via gavage for six weeks. Cardiac function was evaluated using echocardiography, and histopathological changes, oxidative stress markers, mitochondrial damage, and myocardial aging were assessed via H&E staining, immunofluorescence, Western blot, and electron microscopy.

Sper boosted cardiac function in DOX - treated rats, upping EF and SV, and lessening cardiac tissue damage. It cut oxidative stress by reducing MDA levels and boosting SOD activity. Sper also eased mitochondrial damage by enhancing mitochondrial membrane potential and cutting mitochondrial fission proteins (Drp1 and Fis1). Plus, Sper held back myocardial aging by trimming β - galactosidase activity and downregulating p - P53 and p21 expression. At 150 mg/kg/day, Sper worked much like 30 mg/kg/day captopril.

Sper effectively eased DOX - induced heart failure by targeting oxidative stress and aging, showing potential as an adjunct therapy for DOX - related cardiotoxicity. Future research should explore Sper's molecular mechanisms and clinical efficacy.