Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced pulmonary fibrosis (RIPF), is a side effect of radiotherapy for lung cancer and esophageal cancer. Pulmonary macrophages, as a kind of natural immune cells maintaining lung homeostasis, play a key role in the whole pathological process of RILI. In the early stage of RILI, classically activated M1 macrophages secrete proinflammatory cytokines to induce inflammation and produce massive reactive oxygen species (ROS) through ROS-induced cascade to further impair lung tissue. In the later stage of RILI, alternatively activated M2 macrophages secrete profibrotic cytokines to promote the development of RIPF. The roles of macrophage in the pathogenesis of RILI and the related potential clinical applications are summarized in this review.
Humans ; Lung/radiation effects* ; Lung Injury/physiopathology* ; Macrophages/metabolism* ; Radiation Injuries ; Radiation Pneumonitis/etiology* ; Radiotherapy/adverse effects*

OBJECTIVETo study the effect of radiation injury on nitric oxide (NO) concentration in mouse peripheral blood and liver.

METHODSNIH mice were subjected to gamma-ray exposure at 9.0 Gy and transferred immediately in room temperature condition. NO concentrations in the liver and peripheral blood were examined before and at different time points after the exposure.

RESULTSCompared to that before exposure, NO concentration in the peripheral blood and liver significantly increased after gamma-ray exposure. NO concentration in the peripheral blood began to increase 3 h after the exposure, but that in the liver increased till 6 h after the exposure.

CONCLUSIONRadiation can cause the increase of NO concentration in the peripheral blood and liver, but different tissues may exhibit different response intensities to radiation.

Animals ; Gamma Rays ; Liver ; metabolism ; radiation effects ; Male ; Mice ; Nitric Oxide ; blood ; metabolism ; Radiation Injuries, Experimental ; blood ; metabolism ; Time Factors

Wound combined with total body irradiation (TBI) injury results in impairment of tissue repair and delayed processes of healing, so it has been considered as an important and representative model of impaired wound healing, but the mechanism is not fully clarified. Fibroblasts in wound are the most important cells participating in tissue repair, whereas its radiosensitivity is not high. To understand whether TBI injury has direct damaging effects on fibroblasts in wound, fibroblasts in wound combined with TBI injury and in wound of simple incision injury were isolated and cultured, and parameters associated with tissue repair were determined. The results showed that the abilities of proliferation, attachment and adhesion of fibroblasts isolated from wounds combined with TBI injury significantly decreased as compared with those of simple incision injury, nevertheless, apoptotic ratio of fibroblasts isolated from wounds combined with TBI injury increased significantly. These data suggest that TBI injury may cause direct damaging effects on fibroblasts in wounds, which might be one of the dominant reasons for impairment of wound healing when it is combined with TBI injury.
Animals ; Disease Models, Animal ; Fibroblasts ; metabolism ; physiology ; radiation effects ; Radiation Injuries, Experimental ; metabolism ; Rats ; Rats, Wistar ; Skin ; injuries ; Whole-Body Irradiation ; Wound Healing ; physiology

The expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)2 in the irradiated brain was examined to test how a single high dose radiation, similar to that used for intraoperative radiation therapy given to the normal cerebrum, can affect the vascular endothelium. After a burr hole trephination in the rat skull, the cerebral hemisphere was exposed to a single 10 Gy dose of gamma rays, and the radiation effect was assessed at 1, 2, 4, 6, and 8 weeks after irradiation. His-tological changes, such as reactive gliosis, inflammation, vascular proliferation and necrosis, were correlated with the duration after irradiation. Significant VEGF and FGF2 expression in the 2- and 8-week were detected by enzyme-linked immunosorbent assay quantification in the radiation group. Immunohistochemical study for VEGF was done and the number of positive cells gradually increased over time, compared with the sham operation group. In conclusion, the radiation injuries consisted of radiation necrosis associated with the expression of VEGF and FGF2. These findings indicate that VEGF and FGF2 may play a role in the radiation injuries after intraoperative single high-dose irradiation.
Animals ; Brain/metabolism/pathology/radiation effects ; Brain Injuries/etiology/*metabolism/*pathology ; Fibroblast Growth Factor 2/*metabolism ; Necrosis ; Radiation Injuries/*pathology ; Radiosurgery/*adverse effects ; Rats ; Rats, Sprague-Dawley ; Up-Regulation/radiation effects ; Vascular Endothelial Growth Factor A/*metabolism

In the present study, the detrimental effect of beta-emission on pig skin was evaluated. Skin injury was modeled in mini-pigs by exposing the animals to 50 and 100 Gy of beta-emission delivered by 166Ho patches. Clinicopathological and immunohistochemical changes in exposed skin were monitored for 18 weeks after beta-irradiation. Radiation induced desquamation at 2~4 weeks and gradual repair of this damage was evident 6 weeks after irradiation. Changes in basal cell density and skin depth corresponded to clinically relevant changes. Skin thickness began to decrease 1 week after irradiation, and the skin was thinnest 4 weeks after irradiation. Skin thickness increased transiently during recovery from irradiation-induced skin injury, which was evident 6~8 weeks after irradiation. Epidermal expression of nuclear factor-kappa B (NF-kappaB) differed significantly between the untreated and irradiated areas. One week after irradiation, cyclooxygenase-2 (COX-2) expression was mostly limited to the basal cell layer and scattered among these cells. High levels of COX-2 expression were detected throughout the full depth of the skin 4 weeks after irradiation. These findings suggest that NF-kappaB and COX-2 play roles in epidermal cell regeneration following beta-irradiation of mini-pig skin.
Animals ; Cyclooxygenase 2/genetics/*metabolism ; *Holmium ; Male ; NF-kappa B/genetics/*metabolism ; Radiation Injuries, Experimental/metabolism/*veterinary ; Skin/metabolism/*radiation effects ; Swine ; Swine, Miniature

BACKGROUNDIn head and neck neoplasm survivors treated with brain irradiation, metabolic alterations would occur in the radiation-induced injury area. The mechanism of these metabolic alterations has not been fully understood, while the alternations could be sensitively detected by proton (1H) nuclear magnetic resonance spectroscopy (MRS). In this study, we investigated the metabolic characteristics of radiation-induced brain injury through a long-term follow-up after radiation treatment using MRS in vivo.

METHODSA total of 12 adult Sprague-Dawley rats received a single dose of 30 Gy radiation treatment to semi-brain (field size: 1.0 cm × 2.0 cm; anterior limit: binocular posterior inner canthus connection; posterior limit: external acoustic meatus connection; internal limit: sagittal suture). Conventional magnetic resonance imaging and single-voxel 1H-MRS were performed at different time points (in month 0 before irradiation as well as in the 1st, 3rd, 5th, 7th, and 9th months after irradiation) to investigate the alternations in irradiation field. N-acetylaspartate/choline (NAA/Cho), NAA/creatinine (Cr), and Cho/Cr ratios were measured in the bilateral hippocampus and quantitatively analyzed with a repeated-measures mixed-effects model and multiple comparison test.

RESULTSSignificant changes in the ratios of NAA/Cho (F = 57.37, P_{g < 0.001), NAA/Cr (F = 54.49, Pg < 0.001), and Cho/Cr (F = 9.78, Pg = 0.005) between the hippocampus region of the irradiated semi-brain and the contralateral semi-brain were observed. There were significant differences in NAA/Cho (F = 9.17, Pt < 0.001) and NAA/Cr (F = 13.04, Pt < 0.001) ratios over time. The tendency of NAA/Cr to change with time showed no significant difference between the irradiated and contralateral sides. Nevertheless, there were significant differences in the Cho/Cr ratio between these two sides.}

CONCLUSIONSMRS can sensitively detect metabolic alternations. Significant changes of metabolites ratio in the first few months after radiation treatment reflect the metabolic disturbance in the acute and early-delayed stages of radiation-induced brain injuries.

Animals ; Aspartic Acid ; analogs & derivatives ; metabolism ; Brain ; radiation effects ; Choline ; metabolism ; Male ; Proton Magnetic Resonance Spectroscopy ; methods ; Radiation Injuries ; diagnosis ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the effect of Liangxuehuoxue Recipe (LXHXF), a compound traditional Chinese medicinal preparation, on the expressions of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in the lung tissue of rats exposed to X-ray radiation.

METHODSSeventy-two Wistar rats were randomized into exposure group (group A, without treatment) and small-, middle- and high-dose LXHXF groups (groups B, C, and D treated with LXHXF at the daily doses of 9, 18, and 36 g/kg, respectively). After X-ray exposure of the right lung at 3 Gy twice a week for 5 consecutive weeks, the rats were sacrificed at the end of the 5th, 12th and 26th weeks, and the lung tissues were taken for immunohistochemistry of the expressions of TNF-α and TGF-β.

RESULTSIn group A, the expression of TNF-α reached the peak level at 5 weeks and TGF-β expression was the highest at 12 and 26 weeks. LXHXF, especially at the middle and high doses, obviously inhibited the expression of TNF-α at 5 weeks; the treatments also resulted in significantly lowered expressions of TGF-β at all the time points of observation as compared with those in group A (P<0.01). The high- and middle-dose groups exhibited no significant difference in the expression levels of TNF-α and TGF-β in the experiment (P>0.05).

CONCLUSIONTreatment with LXHXF can effectively inhibit TNF-α expression in the lung tissue in the early stage following radiation exposure, causing even more obvious inhibitory effect on TGF-β in the later stages. A higher dose of LXHXF produces more significant inhibitory effects on TNF-α and TGF-β expressions.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Lung ; metabolism ; radiation effects ; Male ; Radiation Injuries ; metabolism ; prevention & control ; Radiation-Protective Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation-injured group and Ligustrazine group. After irradiation by 6.0 Gy 60Co gamma-ray, each mouse was orally given 0.1 ml Ligustrazine twice a day for 13 days in Ligustrazine group, and each mouse in radiation injured group was orally given equal amount of saline. On the 3rd, 7th, 14th day after irradiation, bone marrow mono-nuclear cells (BMMNC) were counted, and the expression levels of bPGF and bFGFR in bone marrow were evaluated by immunohistochemistry and flow cytometry analysis respectively. On the 3rd, 7th, 14th day after irradiation, expression of bFGF in bone marrow were significantly lower than in normal group (P<0.05 or P<0.01). Expressions of bFGF and bFGFR were much higher in Ligustrazine treated group than that in the control group (P<0.05 or P<0.01). Ligustrazine potentiate the expression of bFGF and bFGFR in bone marrow MNC to recover the bone marrow hematopoiesis inductive microenvironment, which is one of the mechanisms by which Ligustrazine rebuild the bone marrow hematopoiesis after acute radioactive injury.
Bone Marrow Cells/metabolism ; Fibroblast Growth Factor 2/*biosynthesis ; Hematopoiesis/drug effects ; Pyrazines/*pharmacology ; Radiation Injuries, Experimental/*metabolism ; Radiation-Protective Agents/pharmacology ; Receptors, Fibroblast Growth Factor/*biosynthesis

OBJECTIVETo investigate the role of lung fibroblast activation in radiation-induced lung injury.

METHODSThirty-five male Wistar rats were exposed to a single-dose 30 Gy irradiation of the right hemithorax or sham right lung irradiation. At 1, 7, 14, 28, 56 or 84 days after the irradiation, the rats were sacrificed for examination of alpha-smooth muscle actin (alpha-SMA) expression in the bilateral lung tissues using immunohistochemistry.

RESULTSalpha-SMA expression in fibroblast increased significantly in the out-field and in-field lung tissues within 24 h after irradiation after the irradiation (P<0.001).

CONCLUSIONActivation of the lung fibroblasts occurred within 24 h after irradiation and found in ont-field and in-field lung tissues, suggesting that radiation-induced lung injury may not have an obvious latency.

Actins ; genetics ; metabolism ; Animals ; Fibroblasts ; metabolism ; pathology ; Lung ; cytology ; pathology ; Male ; Radiation Injuries ; pathology ; Rats ; Rats, Wistar

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with ⁶⁰Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit⁺ HSC, and p16 and p38 mRNA expression of c-kit⁺ HSC were detected. RESULTS: Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit⁺ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit⁺ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01). CONCLUSION The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.
Humans ; Mice ; Animals ; Thrombopoietin/metabolism* ; Hematopoietic Stem Cells ; Blood Platelets ; Recombinant Proteins/therapeutic use* ; Radiation Injuries ; RNA, Messenger/metabolism*