scholarly journals Development of hematopoietic syndrome mice model for localized radiation exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. H. Yashavarddhan ◽  
Ajay Kumar Sharma ◽  
Pankaj Chaudhary ◽  
Sania Bajaj ◽  
Sukhvir Singh ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Whole Body ◽  
Stem Cell Markers ◽  
Nuclear Accidents ◽  
Mice Model ◽  
Gm Csf ◽  
Cd 34 ◽  
Tnf Α ◽  
Radiation Induced ◽  
Partial Body

AbstractCurrent models to study the hematopoietic syndrome largely rely on the uniform whole-body exposures. However, in the radio-nuclear accidents or terrorist events, exposure can be non-uniform. The data available on the non-uniform exposures is limited. Thus, we have developed a mice model for studying the hematopoietic syndrome in the non-uniform or partial body exposure scenarios using the localized cobalt60 gamma radiation exposure. Femur region of Strain ‘A’ male mice was exposed to doses ranging from 7 to 20 Gy. The 30 day survival assay showed 19 Gy as LD100 and 17 Gy as LD50. We measured an array of cytokines and important stem cell markers such as IFN-γ, IL-3, IL-6, GM-CSF, TNF-α, G-CSF, IL-1α, IL-1β, CD 34 and Sca 1. We found significant changes in IL-6, GM-CSF, TNF-α, G-CSF, and IL-1β levels compared to untreated groups and amplified levels of CD 34 and Sca 1 positive population in the irradiated mice compared to the untreated controls. Overall, we have developed a mouse model of the hematopoietic acute radiation syndrome that might be useful for understanding of the non-uniform body exposure scenarios. This may also be helpful in the screening of drugs intended for individuals suffering from radiation induced hematopoietic syndrome.

P–443 Effects of capsaicin pre-treatment on ovarian follicle pool, inflammatory and apoptotic pathways against radiation induced ovarian failure

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Akdemir ◽  
M Akpolat ◽  
O Elmas ◽  
M Kececi ◽  
B Cetinkaya
Keyword(s):  
Oxidative Stress ◽  
Ionizing Radiation ◽  
Radiation Exposure ◽  
Ovarian Follicle ◽  
Ovarian Follicles ◽  
Therapeutic Modality ◽  
Whole Body ◽  
Protective Effects ◽  
Radiation Induced ◽  
Pre Treatment

Abstract Study question Is capsaicin effective in preventing radiation induced ovarian follicle loss and premature ovarian failure (POF) in rats? Summary answer Capsaicin pre-treatment before radiotherapy restores especially primordial follicle pool, inhibits atresia of ovarian follicles, may be an acceptable therapeutic modality to prevent radiation induced POF. What is known already Ionizing radiation exposure to pelvic area induces inflammation, oxidative stress, follicular atresia and apoptosis; leading to POF. Phytochemicals were used in animal studies to prevent radiotherapy induced POF because of their antioxidant and anti-inflammatory properties however their potential radio-protective effects in human ovarian follicles are not clear. Capsaicin is the active compound of hot peppers and has anti-inflammatory and antioxidant properties. It was found that low dose capsaicin stimulated ovarian follicular development and proliferation of granulosa cells, inhibited apoptosis of ovarian follicles in pre-pubertal rat ovaries. However, no data exists on radio-protective effects of capsaicin on ovarian follicles. Study design, size, duration Twenty-four young adult Wistar albino female rats were housed under standard conditions (20 ± 1 0C room temperature, 60 ± 10% humidity, and a 12/12-h light/dark cycle) in regular cages and allowed free access to food and water. After 10 days of subcutaneous capsaicin 0,5 mg/kg/day or placebo treatment, animals exposed to total body irradiation of 8.3 Gy using a linear accelerator. Treatment continued for 1 day after irradiation. Participants/materials, setting, methods Rats were randomly divided into four groups: (1) control: non-irradiated rats were injected placebo; (2) capsaicin: non-irradiated rats were injected capsaicin; (3) radiation only (IR): rats were injected placebo before exposure to a single dose of 8.3-Gy whole body radiation; (4) Radiation-capsaicin (IR+CAP): rats were injected capsaicin prior to whole body irradiation and continued for 1 day after irradiation. Rats were sacrificed, blood samples were obtained for biochemical investigations. Ovaries were dissected for histopathological evaluation. Main results and the role of chance Radiation triggered oxidative stress, increased ovarian inflammation, increased follicular apoptosis and diminished ovarian follicle pool. Capsaicin was significantly ameliorated; oxidative stress by decreasing serum total oxidant status, oxidative stress index, disulfide, and malondialdehyde levels (p ≤ 0.001 both); ovarian inflammatory status by decreasing expressions of TNF-α, IL–1β, poly ADP-ribose polymerase–1 (PARP–1) (p = 0.002 both); apoptosis by decreasing expressions of active caspase–3 and p53 (p = 0.015 and p = 0.002 respectively); follicle counts by increasing primordial follicles and decreasing apoptotic follicles (p ≤ 0.001 both) in rats when administered before radiation exposure. Results of our study confirmed previously reported pro-proliferative and anti-apoptotic properties of capsaicin on ovarian follicles. These beneficial effects of capsaicin are demonstrated for the first time on ionizing radiation exposed rat ovaries. Limitations, reasons for caution Present study is a in-vivo rat study and other preclinical studies are needed to confirm our findings before moving forward to human trials. Radio-protective effects of capsaicin on rat ovarian follicles were demonstrated only in short term. Long term effects of capsaicin on folliculogenesis, fertilization and fecundity should be investigated. Wider implications of the findings: Preserving fertility is one of the main goals of successful radiotherapy in terms of quality of life for oncological or hematological diseases. Capsaicin treatment before radiotherapy may be an acceptable therapeutic modality to prevent radiation induced POF and has potential to utilize in clinical application in terms of fertility preservation. Trial registration number 218S876/2019

In Vivo Induction of Cytokine mRNA and Protein in Mice by the Radioprotectant Steroid 5-Androstenediol.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4224-4224
Author(s):  
Marcy B. Grace ◽  
Cheng-Min Chang ◽  
Vijay K. Singh ◽  
Christopher McLeland ◽  
Cynthia E. Inal ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Whole Body ◽  
Hematopoietic Tissue ◽  
Positive Interaction ◽  
Cd11b Expression ◽  
Killer Cells ◽  
Gm Csf ◽  
Radiation Induced ◽  
Cytokine Cascade

Abstract We previously showed 5-androstenediol (5-AED) injected sc enhanced survival in mice exposed to whole-body gamma-irradiation, ameliorated radiation-induced neutropenia in mice, dogs, and monkeys, and induced increases in bone marrow GM-CFC in irradiated mice. Radiation-induced decreases in platelets, natural killer cells, red blood cells, and monocytes were also blunted by the steroid. Administration of 5-AED caused functional activation of circulating granulocytes (phagocytic ability), monocytes (oxidative burst), and natural killer cells (surface CD11b expression). To test our hypothesis that 5-AED acts via initiation of a cytokine cascade in hematopoietic tissue, we performed real time quantitative PCR on spleen samples taken from mice and correlated the results with serum ELISA. PCR was performed for mRNAs of GM-CSF, IL-6, IL-10, IL-12, and IFNg. Spleens and serum were taken at 3 time points: 4 h after 5-AED or vehicle (PEG-400) injection, and 4 or 24 h after irradiation (7.5 Gy whole-body gamma) or sham-irradiation. Each group contained 5 mice. Results were analyzed by 2-way ANOVA for PCR results 4 and 24 h after irradiation, and by a t-test 4 h after injection. Radiation alone induced increases in mRNAs for all cytokines at both 4 and 24 h, except for IFNg, which was not elevated at 4 h. 5-AED alone did not induce a significant increase for any cytokine, but the increases bordered on significance for IL-12 at 4 h after irradiation or sham-irradiation (28 h after injection, p = 0.07), and for GM-CSF 24 h after irradiation or sham-irradiation (48 h after injection, p = 0.08). There was a significant positive interaction between radiation and 5-AED for IL-6, 4 h after irradiation (p = 0.006). The interaction effect bordered on significance for IL-12 4 h after irradiation (p = 0.07) and for GM-CSF 24 h after irradiation (p = 0.10). ELISA for serum cytokine protein was measured for G-CSF, IL-6, IL-10, and IL-12. Results were analyzed by the Mann-Whitney test for exact p-values. IL-6 was not detected in serum. G-CSF was detected 4 and 24 h after irradiation or sham-irradiation only in 5-AED-treated mice. IL-10 and IL-12 were detected only 24 h after irradiation, and the values in 5-AED-treated mice were significantly higher than those in vehicle-treated mice (p = 0.02). The results support our hypothesis that the previously observed increases in numbers of circulating innate immune cells and platelets, and functional activation of granulocytes, monocytes, and NK cells, result from a cytokine cascade induced by 5-AED.

scholarly journals Phenotypic and Functional Characteristics of Exosomes Derived from Irradiated Mouse Organs and Their Role in the Mechanisms Driving Non-Targeted Effects

2020 ◽  
Vol 21 (21) ◽  
pp. 8389
Author(s):  
Seda Tuncay Cagatay ◽  
Ammar Mayah ◽  
Mariateresa Mancuso ◽  
Paola Giardullo ◽  
Simonetta Pazzaglia ◽  
...  
Keyword(s):  
Membrane Vesicles ◽  
Mouse Embryonic Fibroblast ◽  
Whole Body ◽  
Recipient Mouse ◽  
Oxygen Species ◽  
Cellular Viability ◽  
Radiation Induced ◽  
Partial Body ◽  
Embryonic Fibroblast

Molecular communication between irradiated and unirradiated neighbouring cells initiates radiation-induced bystander effects (RIBE) and out-of-field (abscopal) effects which are both an example of the non-targeted effects (NTE) of ionising radiation (IR). Exosomes are small membrane vesicles of endosomal origin and newly identified mediators of NTE. Although exosome-mediated changes are well documented in radiation therapy and oncology, there is a lack of knowledge regarding the role of exosomes derived from inside and outside the radiation field in the early and delayed induction of NTE following IR. Therefore, here we investigated the changes in exosome profile and the role of exosomes as possible molecular signalling mediators of radiation damage. Exosomes derived from organs of whole body irradiated (WBI) or partial body irradiated (PBI) mice after 24 h and 15 days post-irradiation were transferred to recipient mouse embryonic fibroblast (MEF) cells and changes in cellular viability, DNA damage and calcium, reactive oxygen species and nitric oxide signalling were evaluated compared to that of MEF cells treated with exosomes derived from unirradiated mice. Taken together, our results show that whole and partial-body irradiation increases the number of exosomes, instigating changes in exosome-treated MEF cells, depending on the source organ and time after exposure.

scholarly journals Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis

2021 ◽  
Vol 22 (8) ◽  
pp. 4290
Author(s):  
Simonetta Pazzaglia ◽  
Barbara Tanno ◽  
Francesca Antonelli ◽  
Paola Giardullo ◽  
Gabriele Babini ◽  
...  
Keyword(s):  
Radiation Effects ◽  
Critical Role ◽  
Hippocampal Neurogenesis ◽  
Whole Body ◽  
Potential Contribution ◽  
X Rays ◽  
Neurocognitive Dysfunction ◽  
Post Irradiation ◽  
Radiation Induced ◽  
Partial Body

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.

scholarly journals Analysis of a lectin microarray identifies altered sialylation of mouse serum glycoproteins induced by whole-body radiation exposure

2018 ◽  
Vol 60 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Daisuke Iizuka ◽  
Shunsuke Izumi ◽  
Fumio Suzuki ◽  
Kenji Kamiya
Keyword(s):  
Sialic Acid ◽  
Radiation Exposure ◽  
Initial Response ◽  
Sialic Acids ◽  
Whole Body ◽  
Mouse Serum ◽  
Global Changes ◽  
Γ Radiation ◽  
Radiation Induced ◽  
Induced Changes

AbstractMicroarrays containing 45 different lectins were analyzed to identify global changes in the glycosylation of serum glycoproteins from mice exposed to whole-body γ-radiation. The results showed that radiation exposure increased and decreased the relative amounts of α-2,3- and α-2,6-sialic acids, respectively. The expression of α-2,3- and α-2,6-sialyltransferase genes in the liver was analyzed to determine whether changes in their expression were responsible for the sialic acid changes. The increase in α-2,3-sialic acid correlated with St3gal5 upregulation after radiation exposure; however, a decrease in St6gal1 expression was not observed. Analysis of a PCR array of genes expressed in irradiated mouse livers revealed that irradiation did not alter the expression of most of the included genes. These results suggest that glycomic screening of serum glycoproteins using lectin microarrays can be a powerful tool for identifying radiation-induced changes in the post-translational addition of sugar moieties to proteins. In addition, the results indicate that altered sialylation of glycoproteins may be an initial response to acute radiation exposure.

Bestimmung der Augenlinsen - exposition bei Patienten nach einer Radioi odtherapie

2012 ◽  
Vol 51 (03) ◽  
pp. 79-83 ◽  
Author(s):  
J. Claußnitzer ◽  
L. Oehme ◽  
R. Freudenberg ◽  
J. Kotzerke ◽  
M. Andreeff
Keyword(s):  
Radiation Exposure ◽  
Radioiodine Therapy ◽  
Cumulative Exposure ◽  
Whole Body ◽  
Eye Lens ◽  
Radiological Protection ◽  
Radiation Induced ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

SummaryAim: Current reports for the radiation cataracts contained a warning for deterministic effects at 1–2 Gy radiation single exposure for lens. Recently, the German Radiation Protection Board (SSK) published a document (234. SSK-Board) in that threshold dose for radiation cataracts is claimed at 0.5 Gy. The lens of the eye is recognized as one of the most radiosensitive tissues in the human body, and the International Commission on Radiological Protection (ICRP 103) has defined a limit of 150 mSv for its exposure. Recently, the ICRP lowered this limit down to 20 mSv per year. However, this limit does not apply to patients. Therefore, the question of the lens radiation exposure for patients underwent a radioiodine therapy (RIT) is a point at issue. Patients, methods: A total of 41 patients (age: 22–92 years) underwent a radioiodine therapy were included in the study. Optical stimulated luminescence dosimeters were used to measure the radiation exposure. The dosimeters were fastened nearby the patient’s eye lens. The measurement was carried out up to 48 h after radioiodine application and the patients were divided into three groups. Group 1: patients underwent a diagnostic 131I whole body scan (mean activity: 370 MBq); group 2: thyriod carcinoma patients under RIT (mean activity: 3700 MBq); group 3: hyperthyroid patients under RIT (activity: 180–1237 MBq). Results: The cumulative exposure of the eye lens during the stay at the therapy unit (48 h) was 4.8 ± 0.7 mGy in group 1, 24.5–50.5 mGy in group 2 and 2.7–26.3 mGy in group 3, respectively. For the calculation of the expected cumulative dose, including follow-up after patient's dismissal, the effective half-lives were involved. The cumulative doses were obtained to be 6 ± 1 mGy in the first group, 63 ± 15 mGy in the second and 5–148 mGy in the third. Conclusion: The results show that there exists a low risk for radiation cataract in a nuclear medicine therapy unit. After serial radioiodine therapies radiation-induced lens opacity cannot be expected.

scholarly journals Captopril reduces lung inflammation and accelerated senescence in response to thoracic radiation in mice

2021 ◽  
Vol 62 (2) ◽  
pp. 236-248
Author(s):  
Ognoon Mungunsukh ◽  
Jeffy George ◽  
Elizabeth A McCart ◽  
Andrew L Snow ◽  
Joseph J Mattapallil ◽  
...  
Keyword(s):  
Enzyme Inhibitor ◽  
Whole Body ◽  
Inflammatory Factors ◽  
Thoracic Irradiation ◽  
Tnf Α ◽  
Thoracic Radiation ◽  
Radiation Induced ◽  
Accelerated Senescence ◽  
Anti Inflammatory ◽  
Captopril Treatment

ABSTRACT The lung is sensitive to radiation and exhibits several phases of injury, with an initial phase of radiation-induced pneumonitis followed by delayed and irreversible fibrosis. The angiotensin-converting enzyme inhibitor captopril has been demonstrated to mitigate radiation lung injury and to improve survival in animal models of thoracic irradiation, but the mechanism remains poorly understood. Here we investigated the effect of captopril on early inflammatory events in the lung in female CBA/J mice exposed to thoracic X-ray irradiation of 17–17.9 Gy (0.5–0.745 Gy min–1). For whole-body + thoracic irradiation, mice were exposed to 7.5 Gy (0.6 Gy min–1) total-body 60Co irradiation and 9.5 Gy thoracic irradiation. Captopril was administered orally (110 mg kg–1 day–1) in the drinking water, initiated 4 h through to150 days post-irradiation. Captopril treatment increased survival from thoracic irradiation to 75% at 150 days compared with 0% survival in vehicle-treated animals. Survival was characterized by a significant decrease in radiation-induced pneumonitis and fibrosis. Investigation of early inflammatory events showed that captopril significantly attenuated macrophage accumulation and decreased the synthesis of radiation-induced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) pro-inflammatory cytokines in the lungs of irradiated mice. Suppression of IL-1β and TNF-α correlated with an increase of the anti-inflammatory cytokine IL-10 in the spleen with captopril treatment. We also found that captopril decreased markers for radiation-induced accelerated senescence in the lung tissue. Our data suggest that suppression of inflammation and senescence markers, combined with an increase of anti-inflammatory factors, are a part of the mechanism for captopril-induced survival in thoracic irradiated mice.

Radioiodine treatment of feline hyperthyroidism in Germany

2002 ◽  
Vol 41 (06) ◽  
pp. 245-251 ◽  
Author(s):  
M. Knietsch ◽  
T. Spillmann ◽  
E.-G. Grünbaum ◽  
R. Bauer ◽  
M. Puille
Keyword(s):  
Radiation Exposure ◽  
Radiation Protection ◽  
Thyroid Function ◽  
Radioiodine Therapy ◽  
Whole Body ◽  
Radioiodine Treatment ◽  
Normal Thyroid ◽  
Normal Thyroid Function ◽  
Body Activity ◽  
Thyroid Uptake

SummaryAim: Establishment of radioiodine treatment of feline hyperthyroidism in veterinary routine in accordance with German radiation protection regulations. Patients and methods: 35 cats with proven hyperthyroidism were treated with 131I in a special ward. Thyroid uptake and effective halflife were determined using gammacamera dosimetry. Patients were released when measured whole body activity was below the limit defined in the German “Strahlenschutzverordnung”. Results: 17/20 cats treated with 150 MBq radioiodine and 15/15 cats treated with 250 MBq had normal thyroid function after therapy, normal values for FT3 and FT4 were reached after two and normal TSH levels after three weeks. In 14 cats normal thyroid function was confirmed by controls 3-6 months later. Thyroidal iodine uptake was 24 ± 10%, effective halflife 2.5 ± 0.7 days. Whole body activity <1 MBq was reached 13 ± 4 days after application of 131I. Radiation exposure of cat owners was estimated as 1.97 Sv/MBq for adults. Conclusion: Radioiodine therapy of feline hyper-thyroidism is highly effective and safe. It can easily be performed in accordance with German radiation protection regulations, although this requires hospitalisation for approximately two weeks. Practical considerations on radiation exposure of cat owners do not justify this long interval. Regulations for the veterinary use of radioactive substances similar to existing regulations for medical use in humans are higly desirable.

PET/CT

2005 ◽  
Vol 44 (S 01) ◽  
pp. S51-S57 ◽  
Author(s):  
T. Beyer ◽  
G. Brix
Keyword(s):  
Diagnostic Accuracy ◽  
Radiation Exposure ◽  
Dose Reduction ◽  
Pet Imaging ◽  
Clinical Studies ◽  
Review Article ◽  
Whole Body ◽  
High Radiation ◽  
Radiation Burden ◽  
Pet Ct

Summary:Clinical studies demonstrate a gain in diagnostic accuracy by employing combined PET/CT instead of separate CT and PET imaging. However, whole-body PET/CT examinations result in a comparatively high radiation burden to patients and thus require a proper justification and optimization to avoid repeated exposure or over-exposure of patients. This review article summarizes relevant data concerning radiation exposure of patients resulting from the different components of a combined PET/CT examination and presents different imaging strategies that can help to balance the diagnostic needs and the radiation protection requirements. In addition various dose reduction measures are discussed, some of which can be adopted from CT practice, while others mandate modifications to the existing hardand software of PET/CT systems.

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