scholarly journals Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome

2018 ◽  
Vol 96 (5) ◽  
pp. 442-458
Author(s):  
Shereen Mohamed Galal ◽  
Mohamed Khairy Abdel-Rafei ◽  
Hesham Farouk Hasan
Keyword(s):  
White Blood Cells ◽  
Acute Radiation ◽  
Janus Kinase ◽  
Sublethal Dose ◽  
Related Factor ◽  
Acute Radiation Syndrome ◽  
Signal Transducers ◽  
Human Erythropoietin ◽  
Radiation Induced ◽  
Total Body

The present investigation aimed to evaluate the radiomitigative efficacy of the recombinant human erythropoietin (EPO) against acute radiation syndrome (ARS) in a rat model. Rats were irradiated with a single sublethal dose of γ-radiation (7 Gy; total body irradiation; TBI) on the 1st day of experimental course, then received EPO (5000 IU/kg; i.p.) 24 h after irradiation, and rats were observed for 30 days of survival analysis. Administration of EPO improved 30-day survival, alleviated TBI-induced myelosuppression and pancytopenia, by augmenting lymphocytes and other white blood cells in the peripheral blood of rats, while bone marrow and spleen cellularity were restored. EPO post-exposure treatment alleviated hepatotoxicity biomarkers and restored splenic function. EPO abrogated radiation-induced oxidative stress through the upregulation of the cholinergic anti-inflammatory nicotinic acetylcholine receptor (α-7-nAChR) and the pro-survival Janus kinase-2 and signal transducers and activators of transcription JAK-2/STAT-3 signaling mediated via enhancing nuclear factor erythroid-2 related factor-2 (Nrf-2) cytoprotective machinery in liver and spleen of irradiated rats. Moreover, EPO treatment prevented hepatic and splenic apoptosis. The present study establishes the implication of α-7-nAChR–JAK-2/STAT-3–Nrf-2 signaling cascade in the radiomitigative potential of EPO against ARS.

scholarly journals Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256208
Author(s):  
W. Bradley Rittase ◽  
Elizabeth A. McCart ◽  
Jeannie M. Muir ◽  
Roxane M. Bouten ◽  
John E. Slaven ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Total Body Irradiation ◽  
Blood Cells ◽  
Acute Radiation ◽  
Radiation Injuries ◽  
Induced Expression ◽  
Acute Radiation Syndrome ◽  
Radiation Induced ◽  
Total Body ◽  
Captopril Treatment

Our laboratory has demonstrated that captopril, an angiotensin converting enzyme inhibitor, mitigates hematopoietic injury following total body irradiation in mice. Improved survival in mice is correlated with improved recovery of mature blood cells and bone marrow, reduction of radiation-induced inflammation, and suppression of radiation coagulopathy. Here we investigated the effects of captopril treatment against radiation injuries in the Göttingen mini pig model of Hematopoietic-Acute Radiation Syndrome (H-ARS). Minipigs were given captopril orally (0.96 mg/kg) twice daily for 12 days following total body irradiation (60Co 1.79 Gy, 0.42–0.48 Gy/min). Blood was drawn over a time course following irradiation, and tissue samples were collected at euthanasia (32–35 days post-irradiation). We observed improved survival with captopril treatment, with survival rates of 62.5% in vehicle treated and 87.5% in captopril treated group. Additionally, captopril significantly improved recovery of peripheral blood mononuclear cells, and a trend toward improvement in recovery of red blood cells and platelets. Captopril significantly reduced radiation-induced expression of cytokines erythropoietin and granulocyte-macrophage colony-stimulating factor and suppressed radiation-induced acute-phase inflammatory response cytokine serum amyloid protein A. Using quantitative-RT-PCR to monitor bone marrow recovery, we observed significant suppression of radiation-induced expression of redox stress genes and improved hematopoietic cytokine expression. Our findings suggest that captopril activities in the Göttingen minipig model of hematopoietic-acute radiation syndrome reflect findings in the murine model.

scholarly journals Mitigating Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on Hematopoietic Acute Radiation Syndrome after Total-Body Ionizing Irradiation in Mice

2019 ◽  
Vol 192 (6) ◽  
pp. 602 ◽  
Author(s):  
Yong-Jae Kim ◽  
Jinseon Jeong ◽  
Su-Hyun Shin ◽  
Do Young Lee ◽  
Ki-Young Sohn ◽  
...  
Keyword(s):  
Acute Radiation ◽  
Ionizing Irradiation ◽  
Acute Radiation Syndrome ◽  
Total Body

scholarly journals Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome

2019 ◽  
Vol 60 (3) ◽  
pp. 308-317 ◽  
Author(s):  
Michael R Landauer ◽  
Adam J Harvey ◽  
Michael D Kaytor ◽  
Regina M Day
Keyword(s):  
Estrogen Receptor ◽  
Mechanism Of Action ◽  
Total Body Irradiation ◽  
Intramuscular Injection ◽  
Acute Radiation ◽  
Beta Agonist ◽  
Therapeutic Window ◽  
Acute Radiation Syndrome ◽  
Single Intramuscular Injection ◽  
Total Body

Abstract There are no FDA-approved drugs that can be administered prior to ionizing radiation exposure to prevent hematopoietic–acute radiation syndrome (H-ARS). A suspension of synthetic genistein nanoparticles was previously shown to be an effective radioprotectant against H-ARS when administered prior to exposure to a lethal dose of total body radiation. Here we aimed to determine the time to protection and the duration of protection when the genistein nanosuspension was administered by intramuscular injection, and we also investigated the drug’s mechanism of action. A single intramuscular injection of the genistein nanosuspension was an effective radioprotectant when given prophylactically 48 h to 12 h before irradiation, with maximum effectiveness occurring when administered 24 h before. No survival advantage was observed in animals administered only a single dose of drug after irradiation. The dose reduction factor of the genistein nanosuspension was determined by comparing the survival of treated and untreated animals following different doses of total body irradiation. As genistein is a selective estrogen receptor beta agonist, we also explored whether this was a central component of its radioprotective mechanism of action. Mice that received an intramuscular injection of an estrogen receptor antagonist (ICI 182,780) prior to administration of the genistein nanosuspension had significantly lower survival following total body irradiation compared with animals only receiving the nanosuspension (P < 0.01). These data define the time to and duration of radioprotection following a single intramuscular injection of the genistein nanosuspension and identify its likely mechanism of action.

The Acute Radiation Syndrome in Dogs after Total-Body Exposure to a Supralethal Dose of Ionizing Radiation (Co 60 LD 100/88 hours )

1960 ◽  
Vol 13 (5) ◽  
pp. 712 ◽  
Author(s):  
Stanley Wing Handford ◽  
Paul J. Stonestreet ◽  
Paul W. Johnson ◽  
Leonard A. Freedman ◽  
John H. Flint ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Acute Radiation ◽  
Acute Radiation Syndrome ◽  
Total Body

Investigating the Multifaceted Nature of Radiation-Induced Coagulopathies in a Göttingen Minipig Model of Hematopoietic Acute Radiation Syndrome

2021 ◽  
Vol 196 (2) ◽  
Author(s):  
Bernadette Hritzo ◽  
Betre Legesse ◽  
Jerrold M. Ward ◽  
Amandeep Kaur ◽  
Saeed Y. Aghdam ◽  
...  
Keyword(s):  
Acute Radiation ◽  
Acute Radiation Syndrome ◽  
Göttingen Minipig ◽  
Radiation Induced

Stable Mixed Hematopoietic Chimerism in Dogs Conditioned with Donor Antigen, Anti-CD154 Antibody and 100cGy TBI.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5210-5210
Author(s):  
Christoph Jochum ◽  
Mechthild Beste ◽  
Eustacia Zellmer ◽  
Michael A. Harkey ◽  
Scott S. Graves ◽  
...  
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Sublethal Dose ◽  
Mixed Chimerism ◽  
Allergic Reactions ◽  
Donor Cells ◽  
Mucous Membranes ◽  
Hematopoietic Chimerism ◽  
Total Body ◽  
Peripheral White Blood Cells

Abstract Stable mixed chimerism can be established in dogs given a sublethal dose of 200cGy total body irradiation (TBI) before and immunosupression with mycophenolate mofetil (MMF) and Cyclosporine (CSP). When the TBI dose is reduced to 100 cGy, only transient engraftment is observed. Here we asked whether stable engraftment after 100 cGy TBI could be accomplished by first reducing the intensity of host immune responsiveness with the help of an anti-CD154 antibody which blocks the CD40-CD154 pathway. Accordingly, recipients were given a single i.v. injection of 5 mg/kg anti-CD154 antibody (day -5) followed one day later by combined i.v./sc. injections of 107 peripheral white blood cells/kg from their intended DLA-identical littermate marrow donors. TBI, 100cGy (delivered at 7 cGy/min), was given on day 0 followed by infusion of a median of 4.22x108 marrow cells/kg. Postgrafting immunosuppression consisted of MMF (10mg/kg, BID, days 0 to 28) and CSP (15 mg/kg BID, days -1 to 35). Six dogs have been transplanted. Two dogs are too early after transplant for evaluation, while four dogs have been followed for &gt;9, 12, &gt;18 and &gt;26 weeks. All four dogs had initial engraftment. Three of four dogs have continued to show stable mixed donor/host hematopoietic chimerism among lymphocytes and granulocytes from the peripheral blood. One dog rejected the graft 12 weeks after transplantation. All six transplanted dogs are alive and well. Besides mild allergic reactions to the antibody in five of the six dogs (redness of the eyes, skin rashes and dry mucous membranes), no additional side effects attributed to the pretransplant treatment were observed. Data were consistent with previous findings in dogs, in which the costimulatory signal between B7 and CD28 was blocked, and support the hypothesis, that stable marrow allografts would be established by combining non-myeloablative pretransplant host immunosuppression and posttransplant immunosupression of both host and donor cells using MMF and CSP.

scholarly journals Proteomic Evaluation of the Acute Radiation Syndrome of the Gastrointestinal Tract in a Murine Total-body Irradiation Model

2019 ◽  
Vol 116 (4) ◽  
pp. 516-528 ◽  
Author(s):  
Weiliang Huang ◽  
Jianshi Yu ◽  
Jace W. Jones ◽  
Claire L. Carter ◽  
Keely Pierzchalski ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Total Body Irradiation ◽  
Acute Radiation ◽  
Acute Radiation Syndrome ◽  
Total Body
Sign in / Sign up

Export Citation Format

Share Document