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

Gokhale, A and Rwigema, JC and Epperly, MW and Glowacki, J and Wang, H and Wipf, P and Goff, JP and Dixon, T and Patrene, K and Greenberger, JS (2010) Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model. In Vivo, 24 (4). 377 - 385. ISSN 0258-851X

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Gokhale, A
Rwigema, JC
Epperly, MW
Glowacki, J
Wang, Hhow8@pitt.eduHOW80000-0003-0477-2908
Wipf, Ppwipf@pitt.eduPWIPF
Goff, JP
Dixon, T
Patrene, K
Greenberger, JSjoelg@pitt.eduJOELG
Date: 1 January 2010
Date Type: Publication
Journal or Publication Title: In Vivo
Volume: 24
Number: 4
Page Range: 377 - 385
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 0258-851X
MeSH Headings: Animals; Cyclic N-Oxides--therapeutic use; Disease Models, Animal; Dose-Response Relationship, Radiation; Female; Hindlimb; Mice; Mice, Inbred C57BL; Radiation Injuries--drug therapy; Radiation Injuries--prevention & control; Radiation, Ionizing; Radiation-Protective Agents--therapeutic use; Spin Labels; Tibia--drug effects; Tibia--injuries; Tibia--radiography; Wound Healing--radiation effects
Other ID: NLM NIHMS223059, NLM PMC2916688
PubMed Central ID: PMC2916688
PubMed ID: 20668303
Date Deposited: 28 May 2013 15:30
Last Modified: 20 Sep 2022 13:11


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