آیا سایمتدین می تواند به عنوان یک داروی محافظ رادیویی و رادیوپروتکتور مطرح باشد؟ مکانیزم عمل پیشنهادی

An . in vivo micronucleus assay using mouse bone marrow for identifying radioprotective effect of cimetidine is described. The influence of cimetidine, an antagonist to histamine H2 receptor, on the kinetics of low and high LET radiations such as gamma rays and neutron induced micronuclei as well as the clastogenic effects of chemicals such as benzene, ara C and mitomycin C was tested in Swiss albino male mice. Cimetidine was administered at 15 mgjkg i.p 2 hours prior to irradiation to mice exposed to various doses of gamma rays and neutrons and single dose of drugs. Femoral marrow cells were analysed on slides stained with May-Giemsa. Frequency of micronucleated polychromatic erythrocytes (PCEs) and normochro­matic erythrocytes (NCEs) were determined at various time intervals after irradiation. Results obtained indicate that in all cases cimetidine reduced clastogenic effects of both low and high LET radiation by a dose reduction factor (DRF) of 1.5-2. The dose of cimetidine used in these experiments is not toxic for cells. The way in which cimetidine reduces clastogenic effects of radiation might be via radical scavaging mechanism. In order to verify this mechanism of action of cimetidine, protective effects of chemical agents such as benzene, sytosine arabinoside and' mitomycin C was also studied. These drugs produce biological effects via free radical formation. Results indicate that cimetidine show an anticlastogenic effect against these drugs. Radical scavanging mechanism of cimetidine is associated by amplification of glutathion system, DNA repair and cytochrome P450 inhibition.