Goff, JP and Epperly, MW and Dixon, T and Wang, H and Franicola, D and Shields, D and Wipf, P and Li, S and Gao, X and Greenberger, JS
(2011)
Radiobiologic effects of GS-nitroxide (JP4-039) on the hematopoietic syndrome.
In Vivo, 25 (3).
315 - 323.
ISSN 0258-851X
Abstract
Background/Aim: Total-body irradiation (TBI) doses in the range of 2-8 Gy are associated with a drop in peripheral blood counts, decreased bone marrow cellularity, and hematopoietic syndrome. Radiation mitigators must be safe for individuals likely to recover spontaneously. Materials and Methods: Female C57BL/6HNsd mice exposed to 9.0 and 9.15 Gy TBI, received intraperitoneal (10 mg/kg) JP4-039, a novel radiation mitigator, 24 hours after irradiation and were followed for hematopoietic recovery. Results: Irradiated mice showed reduced peripheral blood lymphocytes and neutrophils and bone marrow cellularity at day 5. Serum electrolytes, liver and renal function tests showed no deleterious effect of JP4-039-after irradiation, and no reduction in survival compared to irradiated controls. Marrow recovery measured as cellularity, and hematopoietic colony-forming cells including primitive granulocyte-erythroid-megakaryocyte- monocytes (GEMM), reached pre-irradiation levels by day 30 in JP4-039 treated groups. Mice receiving single or multiple administrations of JP4-039 showed an early return of CFU-GEMM. Conclusion: JP4-039 (GS-Nitroxide) is a safe radiation mitigator in mice warranting studies in larger animals and potentially a Phase I Clinical Trial.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Goff, JP | | | | | Epperly, MW | | | | | Dixon, T | | | | | Wang, H | how8@pitt.edu | HOW8 | 0000-0003-0477-2908 | | Franicola, D | | | | | Shields, D | | | | | Wipf, P | pwipf@pitt.edu | PWIPF | | | Li, S | sol4@pitt.edu | SOL4 | | | Gao, X | | | | | Greenberger, JS | joelg@pitt.edu | JOELG | |
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| Date: |
1 January 2011 |
| Date Type: |
Publication |
| Journal or Publication Title: |
In Vivo |
| Volume: |
25 |
| Number: |
3 |
| Page Range: |
315 - 323 |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Refereed: |
Yes |
| ISSN: |
0258-851X |
| MeSH Headings: |
Animals; Blood Cell Count; Blood Cells--drug effects; Blood Cells--radiation effects; Bone Marrow--pathology; Bone Marrow--radiation effects; Female; Gamma Rays; Hematopoiesis--drug effects; Hematopoiesis--radiation effects; Hematopoietic Stem Cells--drug effects; Hematopoietic Stem Cells--radiation effects; Mice; Mice, Inbred C57BL; Nitrogen Oxides--pharmacology; Radiation-Protective Agents--pharmacology; Survival Analysis; Time Factors; Whole-Body Irradiation--adverse effects; Whole-Body Irradiation--mortality |
| Other ID: |
NLM NIHMS326786, NLM PMC3202418 |
| PubMed Central ID: |
PMC3202418 |
| PubMed ID: |
21576404 |
| Date Deposited: |
31 Jul 2014 20:50 |
| Last Modified: |
26 Sep 2022 16:22 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/22306 |
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