Effect of cimetidine and famotidine on survival of lethally gamma irradiated mice

There has been a major progress in the area of radioprotective agents since the early 1980s in terms of biological and mechanistic evaluation of the large number of naturally occurring or synthesized compounds. This information led to the development of a new generation of derivative compounds. The development of radio protective agents has been the subject of intense research in view of their potential utility in radiation environments like accidental exposure, tumor radiotherapy, space exploration, and even in a nuclear battlefield (1). The sensitivity of whole-body irradiated animals to ionizingradiation in terms of bone marrow death has also been shown to fluctuate due to physiological conditions and the administration of various kinds of drugs. All organ systems are potentially vulnerable to radiation-induced injury, but the hemopoietic and lymphoid systems are especially sensitive. Whole body exposure to doses of 200-1000 cGy is sufficient to produce a severe peripheral blood pancytopenia which results from depletion of the highly sensitive hemopoetic stem and progenitor cells. This leads to infection, hemorrhage, anemia and ultimately death within 30 days (2). Survival in this hemopoetic system dose range can be increased by agents that simulate the function and recovery of the hemopoetic system. The search for chemical agents which protect against tissue damage caused by exposure to ionizing radiation has led to the identification of thiol (sulfhydryl) compounds with marked activity in experimental models (3). Background: Currently available radioprotectors are poorly tolerated in man and the general use of aminothiols is compromised by their side effects. This study was carried out to test and compare the radioprotective potential of cimetidine and famotidine against lethally gamma irradiated NMRI mice. Materials and Methods: Adult male NMRI mice in groups of 10 were exposed to various doses of gamma rays at a dose rate of 93.3 cGy generated from a Co60 source. Mortality was examined daily for 30 days after irradiation. Various doses of gamma rays were used to calculate LD50/30. Different doses of cimetidine and famotidine were used in combination with 8 Gy gamma rays to find out the optimum protecting concentration of either drug. Finally the optimum protecting concentration of either drug was used in combination with various doses of gamma rays. Each experiment was repeated for three times. Results: Results show that mean LD50/30 for radiation alone was found to be 723.7 cGy. When using different doses of cimetidine in combination with 801 cGy gamma rays, the dose of 15 mg/kg cimetidine produced optimum protection, while optimum dose of famotidine was found to be 10 mg/kg. However, LD50/30 obtained with optimum dose of either cimetidine or famotidine led to a DRF of 1.11 and 1.05 respectively. Conclusion: Cimetidine compared to famotidine was found to be more protective against mortality induced by radiation in mice. This effect of cimetidine might be due to its immunomodulatory role and thus protecting bone marrow and lymphoid tissue injuries following whole body gamma irradiation. Iran. J. Radiat. Res., 2008; 5 (4):