Protective Effect of Atorvastatin against Cardiotoxicity and Hematotoxicity Induced by Cyclophosphamide in Rat

Abstract

Background and purpose: Cyclophosphamide (CP) is used as an anti-cancer and immunosuppressive agent and it is accompanied with severe cardiotoxicity and anemia. Atorvastatin (ATV) is a widely used medication in hypercholesterolemia that has antioxidant and anti-inflammatory properties at low dose. The aim of this study was to investigate the protective effect of ATV on cyclophosphamide-induced cardiotoxicity and hematotoxicity in rats. Materials and methods: Thirty two rats were randomly divided into four groups as following: control group that received normal saline; CP group that received CP intraperitonealy single dose (150 mg/kg); the ATV group that were treated through gavage (10 mg/kg) for 10 days; and ATV + CP that received ATV five days before and five days after CP treatment. The animals were killed three days after the last treatment. Results: Administration of CP caused heart damage through increased activity of cardiac marker enzymes, such as CK-MB and LDH. Histological evaluation of heart tissue showed interstitial edema, necrosis, hemorrhage, congestion, and vacuole around the nucleus. The number of red and white blood cells, platelets, hemoglobin and hematocrit significantly decreased in the group that received CP. ATV significantly reduced the amount of oxidative stress enzymatic activity and heart tissue damage and preserved blood cell counts induced by CP. Conclusion: These findings prove the protective role of ATV on CP-induced cardiotoxicity and hematotoxicity in mice.

Keywords

• cyclophosphamide
• cardiotoxicity
• hematoxicity
• atorvastatin
• antioxidant