Grape Seed and Skin Extract Protects Against Experimentally Cisplatin Chemotherapy-Induced Oxidative Stress and Metabolic Troubles in Rat Muscle

Cisplatin is a widely used antineoplastic agent that also displays toxic side effects. The present study evaluates grape seed and skin extract (GSSE) as a putative protective agent against cisplatin-induced muscle toxicity in rats. Animals were pretreated with a high dosage of GSSE (2.5 g/kg) for 8 days and administered a single dose of cisplatin (5 mg/kg) on the 4th day. Analyses were performed in blood and skeletal muscle. Lipoperoxidation, protein carbonylation, antioxidant enzyme activities (catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD)), reactive oxygen species (ROS; H2O2 and O-2(-)), intracellular mediators (ionizable calcium, free iron, nitric oxide, and magnesium), and metabolic enzymes activities (acetylcholinesterase, creatine kinase, lactate dehydrogenase, lipase, and xanthine oxidase) from muscle tissue were evaluated. Plasma biomarkers and lipidemia were also determined. Cisplatin increased muscle lipid and protein oxidation, ROS, and intracellular mediators such as calcium, nitric oxide, and iron, but decreased magnesium and antioxidant enzyme activities (CAT, SOD, and POD). Furthermore, cisplatin elevated metabolic enzyme activities such as lactate dehydrogenase, xanthine oxidase, and lipase, but depressed creatine kinase and acetylcholinesterase activities. Cisplatin structurally altered the typical muscle histomorphology. In plasma, cisplatin induced a disturbance in electrolyte levels and an increase in creatinine, urea, and uric acid. Cisplatin also increased the plasma lipid profile, metabolic enzyme activities, transaminases, and bilirubin, but decreased albumin. All these disturbances were corrected by GSSE. GSSE efficiently protected muscle from all deleterious effects induced by cisplatin treatment, and should be envisaged as an efficient adjuvant chemotherapy in the treatment of cisplatin-induced muscle toxicity.