Animals ; Decompression Sickness ; Gamma Rays/adverse effects* ; Lung/radiation effects* ; Lung Injury ; Male ; Rats ; Rats, Sprague-Dawley

There is still a need for better protection against or mitigation of the effects of ionizing radiation following conventional radiotherapy or accidental exposure. The objective of our current study was to investigate the possible roles of matrix metalloproteinase inhibitor, ilomastat, in the protection of mice from total body radiation (TBI), and the underlying protective mechanisms. Ilomastat treatment increased the survival of mice after TBI. Ilomastat pretreatment promoted recovery of hematological and immunological cells in mice after 6 Gy γ-ray TBI. Our findings suggest the potential of ilomastat to protect against or mitigate the effects of radiation.
Acute Radiation Syndrome ; blood ; immunology ; prevention & control ; Animals ; Blood Cells ; drug effects ; radiation effects ; Dose-Response Relationship, Drug ; Gamma Rays ; adverse effects ; Hydroxamic Acids ; therapeutic use ; Indoles ; therapeutic use ; Matrix Metalloproteinase Inhibitors ; therapeutic use ; Mice ; Radiation Injuries, Experimental ; blood ; immunology ; prevention & control ; Radiation-Protective Agents ; therapeutic use ; Spleen ; drug effects ; immunology ; radiation effects ; Survival Analysis ; Whole-Body Irradiation

OBJECTIVETo study the blood enriching effects of Paeoniae Radix Rubra and Paeoniae Radix Alba, paeoniflorin and albiflorin on mouse model of blood deficiency caused by γ-ray radiation.

METHODBuild mouse model of blood deficiency induced by γ-ray radiation. Paeoniae Radix Rubra and Paeoniae Radix Alba were given during modeling. The amount of WBC was detected af- ter the treatment. Based on the result of WBC and paeoniflorin content, albiflorin content in Paeoniae Radix Rubra and Paeoniae Radix Alba, the same model and the same method were used to comparatively study the effect of blood enriching of paeoniflorin and albiflorin.

RESULTOn the 7th day, the amount of WBC in model mice treated with 2 g x kg(-1) Paeoniae Radix Alba and 2 g x kg(-1) Paeoniae Radix Rubra significantly increased compared with that of model group (P < 0.05). In another experiment with the same model, the amount of WBC in model mice treated with 120 mg x kg(-1) paeoflorin and 120 mg x kg(-1) albiflorin significantly increased (P < 0.05) compared with that of model group on the 7th day. On the 10th day, the amount of WBC in rats treated with 120 mg x kg(-1) paeoflorin increased significantly (P < 0.05) compared with that of model group. Compared with the same dose of paeoniflorin, the amount of WBC in mice treated with albiflorin had no significant difference.

CONCLUSIONAll Paeoniae Radix Alba, Paeoniae Radix Rubra, paeoniflorin and al- biflorin can raise the amount of WBC and have the effect of enriching blood induced by radiation, while paeoniflorin and albiflorin have a similar result in this model. The result indicated that both paeoniflorin and albiflorin are effective constituents in Paeoniae Radix Alba, and paeoniflorin work as the common effective constituent in both Paeoniae Radix Rubra and Paeoniae Radix Alba.

Animals ; Bridged-Ring Compounds ; pharmacology ; Gamma Rays ; adverse effects ; Glucosides ; pharmacology ; Leukocyte Count ; Leukocytes ; cytology ; drug effects ; radiation effects ; Male ; Mice ; Monoterpenes ; pharmacology ; Rats

This study presents the intercomparison of the outdoor environmental gamma dose rates measured using a NaI (Tl) based survey meter along with thermoluminescent dosimeters (TLDs) and estimation of excess lifetime cancer risk (ELCR), for the inhabitants of Poonch division of the Azad Kashmir, Pakistan. CaF2: Dy (TLD-200) card dosimeters were installed at height of 1 m from ground at fifteen different locations covering the entire Poonch division comprising of three districts. During three distinct two month time periods within the six month study period, all the installed dosimeters were exposed to outdoor environmental gamma radiations, retrieved and read out at Radiation Dosimetry Laboratory, Health Physics Division, PINSTECH laboratory, Islamabad. The ambient outdoor gamma dose rate measurements were also taken with NaI (Tl) based portable radiometric instrument at 1 m above the ground. To estimate the annual gamma doses, NaI (Tl) based survey data were used for one complete year following the deployment of the dosimeters. The mean annual gamma dose rates measured by TLDs and survey meter were found as 1.47±0.10 and 0.862±0.003 mGy/y respectively. Taking into account a 29% outdoor occupancy factor, the annual average effective dose rate for individuals was estimated as 0.298±0.04 and 0.175±0.03 mSv/y by TLDs and survey meter, respectively. For outdoor exposure, the ELCR was calculated from the TLD and survey meter measurements. The environmental outdoor average annual effective dose obtained in present study are less than the estimated world average terrestrial and cosmic gamma ray dose rate of 0.9 mSv/y reported in UNSCEAR 2000. The possible origins of gamma doses in the area and incompatibilities of results obtained from the two different measurement techniques are also discussed.
Gamma Rays ; adverse effects ; Humans ; Neoplasms ; etiology ; Pakistan ; Radiation Monitoring ; instrumentation

The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.
Animals ; Antigens, CD147/*metabolism ; Brain/blood supply/metabolism/pathology/*radiation effects ; Brain Injuries/metabolism/pathology ; Caspase 3/metabolism ; Gamma Rays/*adverse effects ; Immunohistochemistry ; Male ; Microscopy, Electron, Transmission ; Parietal Lobe/metabolism/pathology/radiation effects ; Radiation Injuries, Experimental/metabolism ; Radiosurgery/adverse effects ; Rats ; Rats, Wistar ; Time Factors ; Vascular Endothelial Growth Factor A/*metabolism

OBJECTIVETo study the protective effects of puerarin on 60Co-y-induced acute injury of sertoli cells of testis in mice and the mechanisms for its radiation protection.

METHODSForty male Wistar mice were randomly divided into four groups, i. e., the normal group, the model group, the low dose puerarin group, and the high dose puerarin group, respectively, 10 in each. The lower abdomen and scrotal area of mice were irradiated with a single dose of 8 Gy 60Co-gamma ray for 517 s in the model and two puerarin groups. Twenty-four h after modeling, different concentrations of puerarin (at the daily dose of 230 and 450 mg/kg respectively) were given to mice in the low and high dose groups by gastrogavage, once daily for two successive weeks. Equal volume of physiological saline was given to mice in the normal group and the model group, once daily for two successive weeks. The morphology of the testicular tissues was observed. The levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and inhibin beta were determined by ELISA. The relative expressions of Inhibin beta mRNA in the testicular tissues were determined by Real-time quantitative PCR.

RESULTSSertoli cells and spermatogenic cells were injured at different degrees in the model group. They were improved in the low and high dose puerarin groups, more obviously in the high dose puerarin group. Compared with the normal group, the level of serum FSH in the model group was significantly improved, while the serum level of Inhibin beta and the expression of Inhibin beta mRNA obviously decreased, showing statistical difference (P<0.05). Compared with the model group, the levels of serum FSH, Inhibin beta, and the expression of Inhibin beta mRNA were significantly improved in the low and high dose puerarin groups (P<0.05), more obviously in the high dose puerarin group (P<0.01, P<0.05).

CONCLUSIONChinese medicine monomer of puerarin had certain protective effects on 60Co-gamma-induced acute injury of Sertoli cells in mice.

Animals ; Follicle Stimulating Hormone ; blood ; Gamma Rays ; adverse effects ; Inhibins ; metabolism ; Isoflavones ; pharmacology ; Male ; Rats ; Rats, Wistar ; Sertoli Cells ; drug effects ; metabolism ; radiation effects ; Testis ; cytology ; drug effects ; radiation effects

OBJECTIVETo explore the effects of Huqi Extractum (HQE) on the viability and apoptosis in mouse thymic lymphocytes against 60Co radiation.

METHODSThymic lymphocytes were isolated from 4 -8 weeks healthy male Kunming mice and primarily cultured. Then they were divided into the control group, the irradiation group, the low dose HQE group, the medium dose HQE group, and the high dose HQE group. Equal volume of serum free RPMI-1640 culture solution was added in the control group and the irradiation group, while equal volume of HQE solution (at the daily dose of 25, 50, and 100 mg/mL) was respectively added in the low, medium, and high dose HQE groups. Except the control group, those in the rest groups were exposed radiation at a single dose of 5 Gy gamma-ray. Changes of the thymic lymphocytes' viability were measured by MTT colorimetric assay at 12, 24, 36, and 48 h after radiation. The early apoptosis rate was detected using flow cytometry (FCM) after 10-h radiation. The apoptosis was detected using agarose gel electrophoresis to observe the DNA injury after 24-h radiation.

RESULTSThe viability level decreased more obviously in the irradiation group than in the control group at 24 -48 h after radiation (P < 0.01, P < 0.05). The average viability level was obviously higher in the low, medium, and high dose HQE groups than in the irradiation group (P < 0.05) in a dose dependent manner. The early apoptosis rate was obviously lower in the low, medium, and high dose HQE groups than in the irradiation group, with statistical difference shown in the high dose HQE group (P < 0.01). Typical DNA ladder fragments were found in the electrophoresis in all groups except the control group. But the DNA injury was comparatively milder in the low, medium, and high dose HQE groups, with more obvious effects shown in the high dose HQE group.

CONCLUSIONHQE showed protection for the viability of early thymic lymphocytes exposed to the 60CO radiation, and could lower the early apoptosis level.

Animals ; Apoptosis ; drug effects ; radiation effects ; Cell Survival ; drug effects ; radiation effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Gamma Rays ; adverse effects ; Male ; Mice ; Mice, Inbred Strains ; Thymocytes ; drug effects ; radiation effects

This study was aimed to investigate the effect of recombinant human granulocyte colony-stimulating factor(G-CSF) on murine thymocyte emigration and cell cycle alteration after a sublethal dose of gamma-irradiation. Female BALB/c mice were given 6.0 Gy &gamma;-ray total body irradiation and then randomly divided into G-CSF and control groups. Mice in the G-CSF group were injected recombinant human G-CSF 100 µg/(kg·d) subcutaneously once daily for 14 consecutive days and mice in the control group were given the same volume of phosphate buffered solution. Thymocyte cycle alteration and the proportion of apoptosis cells were detected by flow cytometry within 72 hours after irradiation. Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTREC) of the thymic cells at 30 and 60 day after the irradiation. The results showed that at 6 hour after irradiation G-CSF could significantly increase the thymic cells in G(0)/G(1) phase, G-CSF vs control: (82.0 ± 5.0)% vs (75.9 ± 2.8)% (p < 0.05), and decrease the thymic cells in S phase, G-CSF vs control: (10.2 ± 4.8)% vs (15.7 ± 2.3)% (p < 0.05), but G-CSF seemed have no evident effects on the percentage of thymic cells in G(2)/M phase. G-CSF could also protect thymocytes from apoptosis at 6 hour and 12 hour after irradiation the percentages of apoptosis cells in G-CSF group were (11.5 ± 2.4)% and (15.5 ± 3.3)%, respectively, which were significantly lower than that of the control group (16.5 ± 2.2)% and (22.6 ± 0.7)%, respectively (p < 0.05). The sjTREC copy amount was conspicuously higher in G-CSF group than that in the control at 30 day after irradiation (p < 0.01), but the preponderance disappeared 60 days later. It is concluded that G-CSF has a positive effect on the thymic cell cycle alteration to protect thymocytes from apoptosis and enhance the recent thymocyte emigration, which may contribute to the central immune reconstitution after irradiation.
Animals ; Cell Cycle ; drug effects ; radiation effects ; Female ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; pharmacology ; Thymocytes ; drug effects ; radiation effects

This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and &gamma;-ray. 13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were divided into 3 groups: irradiation control group (no any treatment, n = 4), supportive care group (n = 5) and rhG-CSF plus supportive care group (n = 4, abbreviated as rhG-CSF group) in which the beagles were subcutaneously injected with 200 µg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type. The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%. Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia, enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort administered clinical support. The number of colony-forming cells (CFU-GM, CFU-E, and BFU-E) in peripheral blood of rhG-CSF treated canines increased 2-to 5-fold relative to those of the supportive care group on day 3. All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone. It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy mixed neutron and gamma ray.
Animals ; Dogs ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; pharmacology ; Hematopoietic System ; drug effects ; radiation effects ; Neutron Diffraction ; Recombinant Proteins ; administration & dosage ; pharmacology ; Survival Rate

This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.
Acute Radiation Syndrome/drug therapy/*immunology/psychology ; Amifostine/*pharmacology/therapeutic use ; Animals ; Apoptosis/immunology ; Gamma Rays/*adverse effects ; Hippocampus/immunology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Memory/*radiation effects ; Mice ; Mice, Inbred ICR ; Neurogenesis/immunology ; Radiation-Protective Agents/*pharmacology/therapeutic use