Potent radioprotective effect of therapeutic doses of ranitidine and famotidine against gamma - rays induced micronuclei in vivo

ABSTRACT

Previous investigations have revealed, cimetidine, a histamine H2-receptor antagonist, show radioprotective effects against gamma- and neutron-induced micronuclei in bone marrow erythrocytes. In this study, the anticlastogenic effects of famotidine and ranitidine, which act similar to cimetidine as histamine H2-receptor antagonists, was investigated. Materials and Balb/c male mice were injected i.p. with various doses of famotidine and ranitidine two hours before 2 Gy gamma irradiation. Frequency of micronuclei was determined in bone marrow erythrocytes following each treatment. The results indicated that gamma irradiation alone can cause a high frequency of micronuclei formation and decrease cell proliferation ratio. Pre-irradiation injection of famotidine and ranitidine, of various doses, effectively reduced the number of micronucleated polychromatic erythrocytes [MnPCEs], yet has no effect on cell proliferation ratio [PCEs/PCEs+NCEs]. In fact, these two drugs reduce the clastogenic effects of gamma rays, while they are ineffective against the cytotoxic properties of gamma rays. The dose reduction factor [DRF] calculated, shows a DRF=2 for famotidine and a DRF=1.8 for ranitidine which is indicative of a high radioprotective property of these drugs. The mechanism in which these drugs reduce clastogenic effect of gamma radiation is not fully understood. It might be due to their antioxidant and free radical-scavenging properties