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.
|
Authors | Abhay Gokhale, Jean-Claude Rwigema, Michael W Epperly, Julie Glowacki, Hong Wang, Peter Wipf, Julie P Goff, Tracy Dixon, Ken Patrene, Joel S Greenberger |
Journal | In vivo (Athens, Greece)
(In Vivo)
2010 Jul-Aug
Vol. 24
Issue 4
Pg. 377-85
ISSN: 0258-851X [Print] Greece |
PMID | 20668303
(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)
|