The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice

Devorah Goldman, Vitali Alexeev, Elizabeth Lash, Chandan Guha, Ulrich Rodeck, William Fleming

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Bone marrow suppression due to exposure to ionizing radiation is a significant clinical problem associated with radiation therapy as well as with nonmedical radiation exposure. Currently, there are no small molecule agents available that can enhance hematopoietic regeneration after radiation exposure. Here, we report on the effective mitigation of acute hematopoietic radiation syndrome in mice by the synthetic triterpenoid, RTA 408. The administration of a brief course of RTA 408 treatment, beginning 24 h after lethal doses of radiation to bone marrow, significantly increased overall survival. Importantly, treatment with RTA 408 led to the full recovery of steady state hematopoiesis with normalization of the frequency of hematopoietic stem and progenitor cells. Moreover, hematopoietic stem cells from RTA 408-mitigated mice showed lineage-balanced, long-term, multilineage potential in serial transplantation assays, indicative of their normal self-renewal activity. The potency of RTA 408 in mitigating radiation-induced bone marrow suppression makes it an attractive candidate for potential clinical use in treating both therapy-related and unanticipated radiation exposure.

Original languageEnglish (US)
Pages (from-to)338-344
Number of pages7
JournalRadiation Research
Volume183
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

Acute Radiation Syndrome
bone marrow
radiation dosage
mice
stem cells
Hematopoietic Stem Cells
radiation
hematopoiesis
retarding
Bone Marrow
transplantation
regeneration
ionizing radiation
radiation therapy
therapy
Radiation
recovery
Hematopoiesis
dosage
Ionizing Radiation

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation
  • Medicine(all)

Cite this

The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice. / Goldman, Devorah; Alexeev, Vitali; Lash, Elizabeth; Guha, Chandan; Rodeck, Ulrich; Fleming, William.

In: Radiation Research, Vol. 183, No. 3, 01.03.2015, p. 338-344.

Research output: Contribution to journalArticle

Goldman, Devorah ; Alexeev, Vitali ; Lash, Elizabeth ; Guha, Chandan ; Rodeck, Ulrich ; Fleming, William. / The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice. In: Radiation Research. 2015 ; Vol. 183, No. 3. pp. 338-344.
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