Grape Seed and Skin Extract Protects Against Doxorubicin Chemotherapy-Induced Oxidative Stress, Inflammation and Metabolic Enzyme Disturbances in Rat Lung

Doxorubicin (Doxo), a widely used antitumor anthracycline antibiotic, is the angular stone in the treatment of many neoplasic diseases though also displaying toxic side effects. The present study evaluated the ability of grape seed and skin extract (GSSE) to protect against Doxo-induced lung toxicity in rat. Animals were treated with high dosage GSSE (500 mg/kg) for 8 days and administered a single dose of Doxo (20 mg/kg) on the 4th day. At the end of treatment, lungs were collected to evaluate Doxo-induced oxidative stress status, metabolic disturbances, histopathological alterations as well as the putative protection afforded by GSSE. Doxo induced an oxidative stress status as assessed by increased lipoperoxidation and carbonylation. It also increased levels of reactive oxygen species (ROS) and intracellular mediators as calcium, NO and iron but decreased magnesium and antioxidant enzymes activities as catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD). Furthermore, Doxo elevated metabolic enzyme activities as lactate dehydrogenase (LDH), xanthine oxidase (XO) and lipase but depressed creatine kinase (CK) and acetylcholinesterase (AChE) activities. Doxo structurally altered the typical lung histomorphology. Importantly, GSSE efficiently protected the lung from all deleterious effects triggered by Doxo treatment, and should be envisaged as an efficient chemotherapy adjuvant in the treatment of Doxo-induced lung toxicity.