Objective The aim of the present study was to investigate the effects of Grape seed extract (GSE) and exercise training on Doxorubicin (Doxo)-induced cardio, hepato and myo toxicities in healthy rats. Methods Thirty male Wistar rats were randomly divided into five groups and daily treated by intraperitoneal route during two months either with ethanol 10% (Control); Doxo (1.5 mg/kg); Doxo + exercise (1.5 mg/kg + swimming exercise for 30 min twice a week); Doxo + GSE (1.5 mg/kg + GSE 2.5 g/kg); Doxo + GSE + exercise (1.5 mg/kg + GSE 2.5 g/kg + swimming exercise for 30 min twice a week). At the end of the treatment, tissues were collected and processed for the determination of oxidative stress (OS), intracellular mediators, energy fuelling biomarkers, carbohydrate metabolism parameters and muscle histopathology. Results Doxo provoked OS characterised by an increased lipoperoxidation (LPO) and protein carbonylation and decreased antioxidant enzyme activities. Doxo also affected intracellular mediators, disturbed carbohydrate metabolism and energy fuelling in skeletal muscle as assessed by down-regulated Electron Transport Chain (ETC) complex activities leading in fine to altered skeletal muscle structure and function. Conclusion Almost all Doxo-induced disturbances were partially corrected with GSE and exercise on their own and more efficiently with the combined treatment (GSE + exercise).

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