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Radiobiologic effects of GS-nitroxide (JP4-039) on the hematopoietic syndrome

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

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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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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Goff, JP
Epperly, MW
Dixon, T
Wang, Hhow8@pitt.eduHOW80000-0003-0477-2908
Franicola, D
Shields, D
Wipf, Ppwipf@pitt.eduPWIPF
Li, Ssol4@pitt.eduSOL4
Gao, X
Greenberger, JSjoelg@pitt.eduJOELG
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: 13 Apr 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/22306

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