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

In Vivo. 2011 May-Jun;25(3):315-23.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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

Substances

  • JP4-039
  • Nitrogen Oxides
  • Radiation-Protective Agents