Evaluation of Gamma Radiation-Induced Biochemical Changes in Skin for Dose Assesment: A Study on Small Experimental Animals

2018 ◽  
Vol 13 (02) ◽  
pp. 197-202
Author(s):  
Sandeep Kumar Soni ◽  
Mitra Basu ◽  
Priyanka Agrawal ◽  
Aseem Bhatnagar ◽  
Neelam Chhillar
Keyword(s):  
Radiation Dose ◽  
Gamma Radiation ◽  
Radiation Injury ◽  
Acute Radiation ◽  
Dose Assessment ◽  
Whole Body ◽  
Dependent Manner ◽  
Acute Radiation Injury ◽  
Radiation Induced ◽  
Dose Dependent

AbstractObjectiveResearchers have been evaluating several approaches to assess acute radiation injury/toxicity markers owing to radiation exposure. Keeping in mind this background, we assumed that whole-body irradiation in single fraction in graded doses can affect the antioxidant profile in skin that could be used as an acute radiation injury/toxicity marker.MethodsSprague-Dawley rats were treated with CO-60 gamma radiation (dose: 1-5 Gy; dose rate: 0.85 Gy/minute). Skin samples were collected (before and after radiation up to 72 hours) and analyzed for glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPx).ResultsIntra-group comparison showed significant differences in GSH, GPx, SOD, and CAT, and they declined in a dose-dependent manner from 1 to 5 Gy (P value<0.01, r value: 0.3-0.5). LPx value increased (P value<0.01, r value: 0.3-0.5) as the dose increased, except in 1 Gy (P value>0.05).ConclusionsThis study suggests that skin antioxidants were sensitive toward radiation even at a low radiation dose, which can be used as a predictor of radiation injury and altered in a dose-dependent manner. These biochemical parameters may have wider application in the evaluation of radiation-induced skin injury and dose assessment. (Disaster Med Public Health Preparedness. 2019;13:197–202).

Salivary biochemical markers as potential acute toxicity parameters for acute radiation injury

2015 ◽  
Vol 35 (3) ◽  
pp. 221-228 ◽  
Author(s):  
S Soni ◽  
P Agrawal ◽  
N Kumar ◽  
G Mittal ◽  
DK Nishad ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Effect Size ◽  
Total Protein ◽  
Radiation Injury ◽  
Large Population ◽  
Acute Radiation ◽  
Whole Body ◽  
Sprague Dawley ◽  
Acute Radiation Injury ◽  
Before And After

Researchers have been evaluating several biodosimetric/screening approaches to assess acute radiation injury, related to mass causality. Keeping in mind this background, we hypothesized that effect of whole-body irradiation in single fraction in graded doses can affect the secretion of various salivary components that could be used as acute radiation injury/toxicity marker, which can be used in screening of large population at the time of nuclear accidents/disaster. Thirty Sprague Dawley rats treated with whole-body cobalt-60 gamma irradiation of dose 1–5 Gy (dose rate: 0.95 Gy/min) were included in this study. Whole mixed saliva was collected from all animals before and after radiation up to 72 h postradiation. Saliva was analyzed for electrolytes, total protein, urea, and amylase. Intragroup comparison of salivary parameters at different radiation doses showed significant differences. Potassium was significantly increased as the dose increased from 1 Gy to 5 Gy ( p < 0.01) with effect size of difference ( r > 0.5). Sodium was significantly altered after 3–5 Gy ( p < 0.01, r > 0.5), except 1 and 2 Gy, whereas changes in sodium level were nonsignificant ( p > 0.5). Urea, total protein, and amylase levels were also significantly increased as the radiation dose increased ( p < 0.01) with large effect size of difference ( r > 0.5). This study suggests that salivary parameters were sensitive toward radiation even at low radiation dose which can be used as a predictor of radiation injury.

Re-Examination of the Exacerbating Effect of Inflammasome Components during Radiation Injury

2021 ◽  
Author(s):  
W. June Brickey ◽  
Michael A. Thompson ◽  
Zhecheng Sheng ◽  
Zhiguo Li ◽  
Kouros Owzar ◽  
...  
Keyword(s):  
Cellular Response ◽  
Radiation Injury ◽  
Therapeutic Benefit ◽  
Acute Radiation ◽  
Cellular Damage ◽  
Inflammatory Factors ◽  
Experimental Conditions ◽  
Acute Radiation Injury ◽  
Radiation Induced

Radiation can be applied for therapeutic benefit against cancer or may result in devastating harm due to accidental or intentional release of nuclear energy. In all cases, radiation exposure causes molecular and cellular damage, resulting in the production of inflammatory factors and danger signals. Several classes of innate immune receptors sense the released damage associated molecules and activate cellular response pathways, including the induction of inflammasome signaling that impacts IL-1β/IL-18 maturation and cell death. A previous report indicated inflammasomes aggravate acute radiation syndrome. In contrast, here we find that inflammasome components do not exacerbate gamma-radiation-induced injury by examining heterozygous and gene-deletion littermate controls in addition to wild-type mice. Absence of some inflammasome genes, such as caspase-1/11 and Nlrp3, enhance susceptibility of treated mice to acute radiation injury, indicating importance of the inflammasome pathway in radioprotection. Surprisingly, we discover that the survival outcome may be sex-dependent as more inflammasome-deficient male mice are susceptible to radiation-induced injury. We discuss parameters that may influence the role of inflammasomes as radioprotective or radioexacerbating factors in recovery from radiation injury including the use of littermate controls, the sex of the animals, differences in microbiota within the colonies and other experimental conditions. Under the conditions tested, inflammasome components do not exacerbate radiation injury, but rather provide protective benefit.

scholarly journals Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 99
Author(s):  
Weihong Li ◽  
Shixiang Zhou ◽  
Meng Jia ◽  
Xiaoxin Li ◽  
Lin Li ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Candidate Genes ◽  
Radiation Injury ◽  
Acute Radiation ◽  
Dose Assessment ◽  
Healthy Population ◽  
P53 Signaling ◽  
Acute Radiation Injury ◽  
Effective Combination ◽  
Accurate Dose

Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2–24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.

scholarly journals Effect of Mexidol-Vet® on the course and outcome of acute radiation injury in rats

2020 ◽  
Vol 2020 (5) ◽  
pp. 31-37
Author(s):  
Roman Vasil'ev
Keyword(s):  
Experimental Data ◽  
Gamma Radiation ◽  
Radiation Damage ◽  
Radiation Injury ◽  
Acute Radiation ◽  
Therapeutic Action ◽  
Protective Properties ◽  
Acute Radiation Injury ◽  
Membrane Protective Properties

This paper presents experimental data on the effect of the drug Mexidol-Vet® on the course and outcome of acute radiation damage in rats caused by a single, general, external gamma radiation. There was a 20 % decrease in mortality in animals relative to the control values, activation of erythropoiesis, and a decrease in the severity of erythrocytopenia, leukocytopenia, and thrombocytopenia with the use of Mexidol-Vet®. The supposed mechanism of radioprotective and therapeutic action is the pronounced antioxidant and membrane-protective properties of the drug.

scholarly journals Observations on Chimpanzees after Whole-Body Radiation and Homologous Bone Marrow Treatment

Blood ◽  
1959 ◽  
Vol 14 (12) ◽  
pp. 1302-1321 ◽  
Author(s):  
HARVEY ROTHBERG ◽  
EUGENE B. BLAIR ◽  
ALPHONSE C. GOMEZ ◽  
WILBUR MCNULTY
Keyword(s):  
Bone Marrow ◽  
Survival Time ◽  
Radiation Injury ◽  
Acute Radiation ◽  
Whole Body ◽  
Acute Radiation Injury

Abstract 1. Three chimpanzees were given 900 r of whole body radiation followed by transfusion of homologous bone marrow. One animal survived for nearly six months. 2. Five chimpanzees were given 1200 r of whole body radiation; three of them were given homologous bone marrow. There was no difference in survival time of treated animals and of controls. 3. Observations were made on clinical, hematologic, bacteriologic and pathologic aspects of acute radiation injury. 4. There was no evidence of a "take" of the homologous marrow. The significance of the findings is discussed.

scholarly journals Alrn-6924, a Dual Inhibitor of MDMX and MDM2, Transiently Induces Cell Cycle Arrest in Bone Marrow and Prevents Toxicity in Mouse Models of Acute Radiation Injury

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2947-2947
Author(s):  
Allen Annis ◽  
David Sutton ◽  
Manuel Aivado ◽  
Vojislav Vukovic
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Cell Cycle Arrest ◽  
Mouse Models ◽  
Radiation Injury ◽  
Acute Radiation ◽  
Mouse Bone Marrow ◽  
Acute Radiation Injury ◽  
Cycle Arrest ◽  
Radiation Induced

Abstract Background: Myelosuppression is a common sequela of acute radiation injury due to sensitivity of proliferating bone marrow cells to ionizing radiation. ALRN-6924 is a clinical-stage, first-in-class, stabilized cell-permeating alpha-helical peptide drug that disrupts the interaction of the p53 tumor suppressor protein with its endogenous inhibitors, MDMX and MDM2, to induce transient, dose-dependent cell cycle arrest in p53-wild-type tissues. ALRN-6924 is being evaluated in clinical trials as a selective chemoprotection agent for patients with p53-mutant cancers to protect healthy normal cells from chemotherapy while not protecting p53-mutant cancer cells. We tested whether ALRN-6924 may similarly protect against radiation-induced toxicity in mouse models of acute radiation injury. Materials and methods: Activation of p21 (CDKN1A), a cell cycle regulator under transcriptional control of p53, was measured in formalin-fixed mouse bone marrow by immunohistochemistry analysis (IHC). Proliferation and apoptosis in bone marrow were measured by IHC of Ki67 and cleaved PARP, respectively. Cell cycle arrest was measured in the bone marrow of ALRN-6924-treated C57BL/6 mice by flow cytometry using EdU incorporation. Serum levels of macrophage inhibitory cytokine-1 (MIC-1), a biomarker of p53 activation, were measured by ELISA. As a model of radiation-induced toxicity, C57BL/6 mice (n=7/group) were treated with one or more intravenous 2.4 mg/kg doses of ALRN-6924 at 24, 16, 8, or 1 hour (or combinations thereof) or placebo prior to a 15 Gy shielded-body radiation dose and then monitored for body weight (BW) changes. Results: ALRN-6924 induced cell cycle arrest in mouse bone marrow with a maximum effect at 8 hrs post-dose. Repeated doses of ALRN-6924 every 8 hrs elevated p21 levels in bone marrow that correlated with reduced Ki67 positivity and increased serum MIC-1 levels. Treatment-dependent changes in cPARP expression in bone marrow were evident, but minimal in magnitude. In a nonlethal radiation exposure model, ALRN-6924 yielded significant protection from radiation-induced BW loss in a schedule-dependent manner. Placebo-treated mice showed 10% to 15% BW loss five days after irradiation, while mice receiving one or more ALRN-6924 doses 8 hrs prior to irradiation had an average of 4% BW loss (p=0.008, two-sided t test). Conclusions: ALRN-6924 mitigated toxicity in a mouse model of acute radiation injury. The observed radioprotection effect was correlated with cell cycle arrest in bone marrow after one or more doses of ALRN-6924. These results support further investigation of ALRN-6924 as a radioprotective agent. Disclosures Annis: Aileron Therapeutics, Inc.: Current Employment. Sutton: Aileron Therapeutics, Inc.: Consultancy; Kriya Therapeutics: Consultancy; First Light Pharmaceuticals: Consultancy; Cygnal Therapeutics: Consultancy. Aivado: Aileron Therapeutics, Inc.: Current Employment. Vukovic: Aileron Therapeutics, Inc.: Current Employment.

scholarly journals HemaMax™, a Recombinant Human Interleukin-12, Is a Potent Mitigator of Acute Radiation Injury in Mice and Non-Human Primates

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e30434 ◽  
Author(s):  
Lena A. Basile ◽  
Dolph Ellefson ◽  
Zoya Gluzman-Poltorak ◽  
Katiana Junes-Gill ◽  
Vernon Mar ◽  
...  
Keyword(s):  
Radiation Injury ◽  
Acute Radiation ◽  
Interleukin 12 ◽  
Acute Radiation Injury

scholarly journals Effect of genetic variants in FAS and let-7a on radiation-induced intestinal toxicity in the treatment of prostate cancer

2021 ◽  
Author(s):  
Honglei Guo ◽  
Feng Yuan ◽  
Yancui Zhu ◽  
Ling He
Keyword(s):  
Prostate Cancer ◽  
Dependent Manner ◽  
Intestinal Toxicity ◽  
Rectal Volume ◽  
Obvious Association ◽  
Radiation Induced ◽  
Computational Analyses ◽  
Putative Marker ◽  
Dose Dependent

IntroductionThe present study aimed to explore the effects of pri-let-7a-1 rs10739971 and FAS-670 rs1800682 polymorphisms on the pathogenesis of radiation induced intestinal toxicity in prostate cancer (PC) patients.Material and methods380 PC patients with or without signs of intestinal toxicity were enrolled to study the effects of let-7a rs10739971 and FAS-670 rs1800682 polymorphisms on rectal volume and the risk of intestinal toxicity. In addition, real-time PCR, Western-blot analysis, immunohistochemistry, luciferase assays and computational analyses were performed to explore the mechanism underlying the role of let-7a rs10739971 polymorphism in radiation induced intestinal toxicity.ResultsThe let-7a rs10739971 polymorphism but not the FAS-670 rs1800682 polymorphism was closely related to the risk of radiation induced intestinal toxicity featured by a high rectal volume. In addition, there was no obvious association between the rectal volume and the genotype and allele frequencies of FAS -670 rs1800682 and Pri-let-7a-1 rs10739971 polymorphisms. The GG genotype of let-7a rs10739971 polymorphism reduced let-7a expression but enhanced FAS expression. In addition, the intestinal toxicity (-) group showed a much higher level of let-7a and a much lower level of FAS than the intestinal toxicity (+) group. FAS was a virtual target gene of let-7a, which decreased FAS protein expression in a dose-dependent manner.ConclusionsThe GG genotype of pri-let-7a-1 rs10739971 polymorphism could increase the risk of radiation induced intestinal toxicity in PC patients. Therefore, the pri-let-7a-1 rs10739971 polymorphism could be used as a putative marker to predict the risk of intestinal toxicity in PC patients undergoing radiotherapy.

Protection from radiation-induced apoptosis by the radioprotector amifostine (WR-2721) is radiation dose dependent

2014 ◽  
Vol 30 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Rebecca J. Ormsby ◽  
Mark D. Lawrence ◽  
Benjamin J. Blyth ◽  
Katrina Bexis ◽  
Eva Bezak ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Radiation Induced ◽  
Induced Apoptosis ◽  
Dose Dependent
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