Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model.
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.
Gokhale
Abhay
A
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Hillman Cancer Center, Rm. G.5c, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
Rwigema
Jean-Claude
JC
Epperly
Michael W
MW
Glowacki
Julie
J
Wang
Hong
H
Wipf
Peter
P
Goff
Julie P
JP
Dixon
Tracy
T
Patrene
Ken
K
Greenberger
Joel S
JS
D000818:Animals; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006614:Hindlimb; D051379:Mice; D008810:Mice, Inbred C57BL; D011832:Radiation Injuries / Q000188:drug therapy* / Q000517:prevention & control; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011859:Radiography; D013113:Spin Labels; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000293:injuries*; D014945:Wound Healing / Q000528:radiation effects*
D003497:Cyclic N-Oxides; D011837:Radiation-Protective Agents; D013113:Spin Labels; C001803:tempol