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Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model.

Abstract
We studied radioprotection and mitigation by mitochondrial-targeted Tempol (GS-nitroxide, JP4-039), in a mouse injury/irradiation model of combined injury (fracture/irradiation). Right hind legs of control C57BL/6NHsd female mice, mice pretreated with MnSOD-PL, JP4-039, or with amifostine were irradiated with single and fractionated doses of 0 to 20 Gy. Twenty-four hours later, unicortical holes were drilled into the tibiae of both hind legs; at intervals, tibias were excised, radiographed, and processed for histology. Bone wounds irradiated to 20 or 30 Gy showed delayed healing at 21 to 28 days. Treatment with JP4-039 MnSOD-PL or amifostine, before or after single fraction 20 Gy or during fractionated irradiation followed by drilling accelerated wound healing at days 21 and 28. Orthotopic 3LL tumors were not protected by JP4-039 or amifostine. In nonirradiated mice, pretreatment with JP4-039 accelerated bone wound healing. This test system should be useful for the development of new small molecule radioprotectors.
AuthorsAbhay Gokhale, Jean-Claude Rwigema, Michael W Epperly, Julie Glowacki, Hong Wang, Peter Wipf, Julie P Goff, Tracy Dixon, Ken Patrene, Joel S Greenberger
JournalIn vivo (Athens, Greece) (In Vivo) 2010 Jul-Aug Vol. 24 Issue 4 Pg. 377-85 ISSN: 0258-851X [Print] Greece
PMID20668303 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Cyclic N-Oxides
  • Radiation-Protective Agents
  • Spin Labels
  • tempol
Topics
  • Animals
  • Cyclic N-Oxides (therapeutic use)
  • Disease Models, Animal
  • Dose-Response Relationship, Radiation
  • Female
  • Hindlimb
  • Mice
  • Mice, Inbred C57BL
  • Radiation Injuries (drug therapy, prevention & control)
  • Radiation, Ionizing
  • Radiation-Protective Agents (therapeutic use)
  • Radiography
  • Spin Labels
  • Tibia (diagnostic imaging, drug effects, injuries)
  • Wound Healing (radiation effects)

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