Radioprotective Effects of Cimetidine in Mouse Bone Marrow Cells Exposed to γ-rays as Assayed by the Micronucleus Test

Mozdarani, Hossein; Gharbali, Akbar

doi:10.1080/09553009314551291

Cited by 28 publications

(8 citation statements)

References 15 publications

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“…The majority of MN present in cells following high-dose radiation exposure are extra-nuclear DNA fragments arising from acentric chromosome fragments originating from unrepaired or misrepaired DSBs [ 58 ]. Previous studies examining the dose–response relationship for γ and X-ray exposures and mouse bone marrow MN-PCE support a linear or linear-quadratic function for exposures to low to moderate doses of ionizing radiation (e.g., 0.1 to 0.5 Gy) [ 54 , 56 , 59 , 60 , 61 , 62 , 63 ]. More damaging radiations (>1 Gy) have been shown to prolong the erythroblast cell cycle and delay the temporal appearance of radiation-induced MN-PCE in the bone marrow [ 53 , 54 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Dose and Radioadaptive Response Analysis of Micronucleus Induction in Mouse Bone Marrow

Bannister

Mantha

Devantier

et al. 2016

IJMS

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Enhanced cellular DNA repair efficiency and suppression of genomic instability have been proposed as mechanisms underlying radio-adaptive responses following low-dose radiation exposures. We previously showed that low-dose γ irradiation does not generate radio-adaptation by lowering radiation-induced cytogenetic damage in mouse spleen. Since radiation may exert tissue-specific effects, we extended these results here by examining the effects of γ radiation on cytogenetic damage and proliferative index in bone marrow erythrocytes of C57BL/6 and BALB/c mice. In C57BL/6 mice, the induction of micronuclei in polychromatic erythrocytes (MN-PCE) was observed at radiation doses of 100 mGy and greater, and suppression of erythroblast maturation occurred at doses of >500 mGy. A linear dose–response relationship for MN-PCE frequencies in C57BL/6 mice was established for radiation doses between 100 mGy and 1 Gy, with departure from linearity at doses of >1 Gy. BALB/c mice exhibited increased MN-PCE frequencies above baseline following a 20 mGy radiation exposure but did not exhibit radio-sensitivity relative to C57BL/6 mice following 2 Gy exposure. Radio-adaptation of bone marrow erythrocytes was not observed in either strain of mice exposed to low-dose priming γ irradiation (single doses of 20 mGy or 100 mGy or multiple 20 mGy doses) administered at various times prior to acute 2 Gy irradiation, confirming the lack of radio-adaptive response for induction of cytogenetic damage or suppression or erythrocyte proliferation/maturation in bone marrow of these mouse strains.

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Section: Discussionmentioning

confidence: 99%

Dose and Radioadaptive Response Analysis of Micronucleus Induction in Mouse Bone Marrow

Bannister

Mantha

Devantier

et al. 2016

IJMS

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“…Cimetidine was shown to be effective against the clastogenic effects of γ-rays [ 6 , 7 ] and X-rays [ 8 ] in vitro. It was also demonstrated to be protective against γ-rays and neutrons in vivo [ 7 , 9 – 12 ]. Cimetidine was shown to inhibit the activity of suppressor T cells [ 13 ] and was used in radioprotection to help the recovery of the lymphohematopoietic system effectively [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…This supports the hypothesis that cimetidine may afford efficient protection against ionizing radiation or diseases that are characterized by in vivo free radical-mediated oxidative stress mechanisms [ 15 ]. It was shown that cimetidine, ranitidine, and famotidine produced a DRF of 1.5 to 2 against γ-ray-induced micronuclei in mouse bone marrow erythrocytes [ 9 , 16 ]. Cimetidine, compared with famotidine, was found to be more protective against mortality induced by radiation in mice [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Radioprotective effects of cimetidine on rats irradiated by long-term, low-dose-rate neutrons and 60Co γ-rays

Jiang¹,

Wang²,

Shen³

et al. 2017

Military Med Res

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BackgroundCimetidine, 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).MethodsFifty 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 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.ResultsThe 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.ConclusionsThe 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.

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“…A similar decrease in MnPCE induced by -irradiation has been described by other antioxidants such as amifostine, glutathione and cimetidine. 19,20 Treatment of mice with captopril at dose of 10 mg/kg before exposure to 2 Gy radiation reduced the frequency of MnPCE almost 2.18 fold. Among radioprotective agents, amifostine has been evaluated as a powerful radioprotector, but this drug is effective only at high doses which are close to the toxic level (i.e.…”

Section: Discussionmentioning

confidence: 99%

Captopril protects mice bone marrow cells against genotoxicity induced by gamma irradiation

Hosseinimehr

Mahmoudzadeh²,

Akhlagpour

2006

Cell Biochemistry & Function

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The radioprotective effects of captopril were investigated by using the micronucleus test for anticlastogenic and cell proliferation activity. A single intraperitoneal administration of captopril at doses of 10, 25 and 50 mg/kg 1 h prior to gamma irradiation (2 Gy) reduced the frequencies of micronuleated polychromatic erythrocytes (MnPCEs). All three doses of captopril significantly reduced the frequencies of MnPCEs and increased polychromatic erythrocytes (PCE)/PCE+NCE (normochromatic erythrocyte) ratio in mice bone marrow compared to the non-drug-treated irradiated control (p < 0.001). The optimum dose for protection in mouse was 10 mg/kg to protect mice bone marrow 2.18-fold against the clastogenic effects of gamma-irradiation with respect to the non-drug-treated irradiated control. There was a drug dose-response effect of captopril in increasing the PCE/PCE+NCE ratio in bone marrow cells. The maximum protective effect of captopril was at a dose of 25 mg/kg for increasing the PCE/PCE + NCE ratio. Captopril exhibited concentration-dependent antioxidant activity, scavenging > 96% of the 1,1-diphenyl-2-picryl hydrazyl free radicals when used at a concentration of 0.2 mM. In this study captopril reduced lipid peroxidation induced by hydrogen peroxide in mice liver. It appears that captopril, due to its free radical scavenging properties, protects mice bone marrow cells from radiation-induced DNA damage and genotoxicity.

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Radioprotective Effects of Cimetidine in Mouse Bone Marrow Cells Exposed to γ-rays as Assayed by the Micronucleus Test

Cited by 28 publications

References 15 publications

Dose and Radioadaptive Response Analysis of Micronucleus Induction in Mouse Bone Marrow

Dose and Radioadaptive Response Analysis of Micronucleus Induction in Mouse Bone Marrow

Radioprotective effects of cimetidine on rats irradiated by long-term, low-dose-rate neutrons and 60Co γ-rays

Captopril protects mice bone marrow cells against genotoxicity induced by gamma irradiation

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