Purine versus non-purine xanthine oxidase inhibitors against cyclophosphamide-induced cardiac and bone marrow toxicity in rats

Abstract

Background and aim:

Cancer is a fatal and serious disease. Cyclophosphamide (CYC) is a commonly used anticancer drug. Cardiotoxicity and myelotoxicity are life-threatening side effects of CYC treatment. We aimed to evaluate the effect of the xanthine oxidase (XO) inhibitors, allopurinol (ALL) and febuxostat (FEB), on CYC-induced cardio- and hematopoietic toxicity in rats.

Methods:

ALL (100 mg/kg/day) or FEB (10 mg/kg/day) were administered orally to rats in the presence and absence of CYC (200 mg/kg kg i.p. single dose) treatment. Serum creatine kinase-MB creatine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH) activities were estimated. Complete blood counting (CBC), cardiac and bone marrow XO activity, malondialdehyde level, and superoxide dismutase activity were determined. Cardiac and bone marrow histopathological changes were also evaluated.

Results:

ALL and FEB significantly decreased CK-MB and LDH induced by CYC. Disturbed levels of XO, oxidative stress parameters, and CBC were also corrected by both XO inhibitors tested, with amelioration of cardiac histopathological changes caused by CYC. Treatment with FEB, but not ALL, prior to CYC challenges normalized bone marrow histopathological changes.

Conclusion:

These results suggest that both XO inhibitors tested; ALL and FEB can ameliorate CYC-induced cardiotoxicity. However, only FEB can protect against CYC-induced myelotoxicity, whereas ALL, to the contrary, might aggravate it.