Radioprotective effects of cimetidine on rats irradiated by long-term, low-dose-rate neutrons and ^(60)Coγ-rays

Background: Cimetidine, an antagonist of histamine type II receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combined with γ-rays. This study was carried out to evaluate the protective effects of cimetidine on rats exposed to long-term, low-dose-rate neutron and γ-ray combined irradiation(n-γ LDR).Methods: Fifty male Sprague-Dawley(SD) rats were randomly divided into 5 groups: the normal control group, radiation model group, 20mg/(kg·d) cimetidine group, 80mg/(kg·d) cimetidine group and 160mg/(kg·d) cimetidine group(10 rats per group). Except for the normal control group, 40 rats were simultaneously exposed to fission neutrons(^(252)Cf, 0.085 m Gy/h) for 22 h every day and γ-rays(^(60)Co, 0.097Gy/h) for 1.03 h once every three days, and the cimetidine groups were administered intragastrically with cimetidine at doses of 20, 80 and 160mg/kg each day. Peripheral blood WBC of the rats was counted the day following exposure to γ-rays. The rats were anesthetized and sacrificed on the day following exposure to ^(252)Cf for 28 days. The spleen, thymus, testicle, liver and intestinal tract indexes were evaluated. The DNA content of bone marrow cells and concanavalin A(Con A)-induced lymphocyte proliferation were measured. The frequency of micronuclei in polychromatic erythrocytes(f MNPCEs), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione peroxidase(GSH-Px) in the serum and liver tissues were detected.Results: The peripheral blood WBC in the cimetidine groups was increased significantly on the 8th day and the 26 th day compared with those in the radiation model group. The spleen, thymus and testicle indexes of the cimetidine groups were higher than those of the radiation model group. The DNA content of bone marrow cells and lymphocyte proliferation in the cimetidine groups were increased significantly, and fMNPCE was reduced 1.41-1.77 fold in cimetidine treated groups. The activities of SOD and GSH-Px in the cimetidine groups were increased significantly, and the content of MDA in the cimetidine groups was decreased significantly.Conclusions: The results suggested that cimetidine alleviated damage induced by long-term, low-dose-rate neutron and γ combined irradiation via antioxidation and immunomodulation. Cimetidine might be useful as a potent radioprotector for radiotherapy patients as well as for occupational exposure workers.

Background： Cimetidine, an antagonist of histamine type Ⅱ receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combined with γ-rays. This study was carried out to evaluate the protective effects of cimetidine on rats exposed to long-term, low-dose-rate neutron and γ-ray combined irradiation （n-γ LDR）. Methods： Fifty male Sprague-Dawley （SD） rats were randomly divided into 5 groups： the normal control group, radiation model group, 20mg/（kg-d） cimetidine group, 80mg/（kg.d） cimetidine group and 160mg/（kg.d） cimetidine group （10 rats per group）. Except for the normal control group, 40 rats were simultaneously exposed to fission neutrons （2S2Cf, 0.085mGy/h） for 22h every day and y-rays （60Co, 0.097Gy/h） for 1.03h once every three days, and the cimetidine groups were administered intragastrically with cimetidine at doses of 20, 80 and 160mg/kg each day. Peripheral blood WBC of the rats was counted the day following exposure to y-rays. The rats were anesthetized and sacrificed on the day following exposure to 252Cf for 28 days. The spleen, thymus, testicle, liver and intestinal tract indexes were evaluated. The DNA content of bone marrow cells and concanavalin A （ConA）-induced lymphocyte proliferation were measured. The frequency of micronuclei in polychromatic erythrocytes （fMNPCEs）, superoxide dismutase （SOD）, malondialdehyde （MDA）, and glutathione peroxidase （GSH-Px） in the serum and liver tissues were detected. Results： The peripheral blood WBC in the cimetidine groups was increased significantly on the 8th day and the 26th day compared with those in the radiation model group. The spleen, thymus and testicle indexes of the cimetidine groups were higher than those of the radiation model group. The DNA content of bone marrow cells and lymphocyte proliferation in the cimetidine groups were increased significantly, and fMNPCE was reduced 1.41-1.77 fold in cimetidine treated groups. The activities of SOD and GSH-Px in the cimetidine groups were increased significantly, and the content of MDA in the cimetidine groups was decreased significantly. Conclusions： The results suggested that cimetidine alleviated damage induced by long-term, low-dose-rate neutron and y combined irradiation via antioxidation and immunomodulation. Cimetidine might be useful as a potent radioprotector for radiotherapy patients as well as for occupational exposure workers.