ABSTRACT
Cyclophosphamide [CYP] is widely used as an antineoplastic and an immunosuppressive drug. However, it has been found to cause DNA damage in normal tissues as well. Captopril [CAP], an angiotensin converting enzyme inhibitor, was reported to have a potential protective effect on the genotoxic effect of CYP possibly through its antioxidant effect. The aim of the present work is to experimentally detect the genotoxic effect of cyclophosphamide using in vivo micronuclei assay in albino mice bone marrow polychromatic erythrocytes and to test the protective effect of captopril on reducing the genotoxicity of CYP. In the present study thirty adult male albino mice were equally divided into six groups. Group I [control group] animals received single physiological saline, group II mice received single injection of captopril [CAP] [50mg/kg], group III animals received single injection of 25mg/kg cyclophosphamide [CYP] dissolved in physiological saline, group IV mice received single injection of 50 mg/kg CYP dissolved in physiological saline, and groups V and VI were the same as group III and IV but CYP injection was preceded by CAP [50mg/kg] injection. The number of micronucleated polychromatic erythrocytes [MNPCEs] was determined in 1000 polychromatic cells from bone marrow smears obtained after sacrificing the animals 24 hrs from exposure to CYP or the control substance. Statistical comparison of the different groups showed that the difference between group I and II was not statistically significant [P=0.106], indicating that CAP does not induce genotoxicity. Whereas, comparing Groups III, IV to group I showed that the difference was statistically significant [P=0.013, 0.00021] It was observed that CYP increased the number of MNPCEs in a dose dependent way. Comparison of groups V and Vito groups III and IV respectively showed a significantly lower number of MNPCEs confirming a protective effect of CAP when administered prior to CYP. The results of the present study confirm a protective role of CAP and support the possibility of administration of captopril prior to cyclophosphamide to ameliorate its genotoxic effect and the possibility to develop secondary cancers