title: Radioprotective effects of cimetidine on rats irradiated by long-term, low-dose-rate neutrons and60Co γ-rays.
abstract: 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).
  
  
  
  Fifty male Sprague-Dawley (SD) rats were randomly divided into 5 groups: the normal control group, radiation model group, 20 mg/(kg · d) cimetidine group, 80 mg/(kg · d) cimetidine group and 160 mg/(kg · d) cimetidine group (10 rats per group). Except for the normal control group, 40 rats were simultaneously exposed to fission neutrons (252Cf, 0.085 mGy/h) for 22 h every day and γ-rays (60Co, 0.097 Gy/h) for 1.03 h once every three days, and the cimetidine groups were administered intragastrically with cimetidine at doses of 20, 80 and 160 mg/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 to252Cf 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.
  
  
  
  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.
  
  
  
  The results suggested that cimetidine alleviated damage induced by long-term, low-dose-rate neutron and γ combined irradiationviaantioxidation and immunomodulation. Cimetidine might be useful as a potent radioprotector for radiotherapy patients as well as for occupational exposure workers.
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Ding-Wen
authors.initials: DW
authors.lastname: Jiang
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Wang
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Xian-Rong
authors.initials: XR
authors.lastname: Shen
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Qian
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Deng-Yong
authors.initials: DY
authors.lastname: Hou
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Liu
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ren
authors.affiliation: The PLA Key Laboratory of Biological Effect and Medical Protection on Naval Vessel Special Environment, Naval Medical Research Institute, Xiangyin Road 880, Shanghai, 200433 China.
authors.forename: Ke-Xian
authors.initials: KX
authors.lastname: Li
mesh_terms: D000818:Animals; D002927:Cimetidine / Q000494:pharmacology / Q000627:therapeutic use*; D005720:Gamma Rays / Q000009:adverse effects*; D005979:Glutathione Peroxidase / Q000032:analysis / Q000097:blood; D007422:Intestines / Q000187:drug effects; D007958:Leukocyte Count / Q000706:statistics & numerical data; D008099:Liver / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000097:blood; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects; D013482:Superoxide Dismutase / Q000032:analysis / Q000097:blood; D013737:Testis / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects
chemical_list: D011837:Radiation-Protective Agents; D008315:Malondialdehyde; D002927:Cimetidine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Antioxidation; Cimetidine; Immunomodulation; Micronuclei; Radioprotection