Salen Mn complexes mitigate radiation injury in normal tissues. Anticancer Agents Med Chem 2011 May 01;11(4):359-72
Date
04/02/2011Pubmed ID
21453241Pubmed Central ID
PMC3814176DOI
10.2174/187152011795677490Scopus ID
2-s2.0-79958116231 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown "mito-protective" properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study.
Author List
Rosenthal RA, Fish B, Hill RP, Huffman KD, Lazarova Z, Mahmood J, Medhora M, Molthen R, Moulder JE, Sonis ST, Tofilon PJ, Doctrow SRAuthor
Meetha Medhora Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsEthylenediamines
Humans
Organometallic Compounds
Oxidative Stress
Radiation Injuries
Radiation Injuries, Experimental
Superoxide Dismutase
