Biochemical, Histological, and Ultrastructural Studies of the Protective Role of Vitamin E on Cyclophosphamide-Induced Cardiotoxicity in Male Rats

Background: Cyclophosphamide (CP) (Cytoxan or Endoxan) is an efficient anti-tumor agent, widely used for the treatment of various neoplastic diseases. The study aimed to investigate the protective role of vitamin E (vit E) in improving cardiotoxicity in rats induced by CP. Materials and methods: Forty male Wistar rats were divided randomly into four experimental groups (each consisting of ten rats); the control group was treated with saline. The other three groups were treated with vit E, CP, and the combination of vit E and CP. Serum lipid profiles, enzyme cardiac biomarkers, and cardiac tissue antioxidants were evaluated, as well as histological and ultrastructure investigations. Results: CP-treated rats showed a significant increase in serum levels of cardiac markers (troponin, CK, LDH, AST, and ALT), lipid profiles, a reduction in the antioxidant enzyme activities (CAT, SOD, and GPx), and an elevation in the level of lipid peroxidation (LPO). The increase in the levels of troponin, LDH, AST, ALP, and triglycerides is a predominant indicator of cardiac damage due to the toxic effect of CP. The biochemical changes parallel cardiac injuries such as myocardial infarction, myocarditis, and heart failure. Vitamin E played a pivotal role, as it attenuated most of these changes because of its ability to scavenge free radicals and reduce LPO. In addition, vit E was found to improve the histopathological alterations caused by CP where no evidence of damage was observed in the cardiac architecture, and the cardiac fibers had regained their normal structure with minimal hemorrhage. Conclusions: As a result of its antioxidant activity and its stabilizing impact on the cardiomyocyte membranes, vit E is recommended as a potential candidate in decreasing the damaging effects of CP.