Protective Effect of Carvacrol Against Oxidative Stress and Heart Injury in Cyclophosphamide-Induced Cardiotoxicity in Rat

Abstract

Possible protective effects of carvacrol (Car) against cyclophosphamide (CP)-induced cardiotoxicity was examined in this study. Experimental groups of the rats were randomly divided into 13 groups, each including seven animals: Group 1 (control) treated with saline; groups 2, 3, and 4 treated with 50, 100, or 150 mg/kg of CP, respectively; group 5 treated with 0.5 mL olive oil; groups 6 and 7 treated with 5.0 and 10 mg/kg of Car, respectively; groups 8, 9, or 10 treated with respective CP plus 5.0 mg/kg of Car; and groups 11, 12, or 13 treated with respective CP plus 10 mg/kg of Car. Serum alanine transaminase (ALT), aspartat transaminase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase-MB (CK-MB), total oxidant state (TOS), oxidative stress index (OSI), and levels were high only in the CP groups. There was a dose-dependence on the CP-induced cardiotoxicity. Hemorrhage, inflammatory cell infiltration and the separation of the muscle fibers in the heart tissue supported the biochemical data. With 5.0 and 10 mg/kg Car, there was an important decrease in the CP toxicity and this was related to the oxidative and nitrosative stress in the CP-induced cardiotoxicity. Reduced inflammation and lipid peroxidation in the heart tissue and increase of serum glutathione (GSH) and total antioxidant capacity (TAS) levels were found when carvacrol was applied. Based on these findings, it could be proposed that Car was a strong candidate in preventing the CP-induced cardiotoxicity but further clinical studies should be done in order to verify its application on humans.