A Synthetic Superoxide Dismutase/Catalase Mimetic EUK-207 Mitigates Radiation Dermatitis and Promotes Wound Healing in Irradiated Rat Skin

被引：49
作者：
Doctrow, Susan R. [1 ]
Lopez, Argelia [2 ]
Schock, Ashley M. [2 ]
Duncan, Nathan E. [2 ]
Jourdan, Megan M. [2 ]
Olasz, Edit B. [2 ]
Moulder, John E. [3 ]
Fish, Brian L. [3 ]
Maeder, Marylou [3 ]
Lazar, Jozef [2 ]
Lazarova, Zelmira [2 ]
机构：
[1] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA
[2] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA
[3] Med Coll Wisconsin, Radiat Oncol Ctr Med Countermeasures Radiol Terro, Milwaukee, WI 53226 USA
来源：
JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2013年 / 133卷 / 04期
关键词：
MITOCHONDRIAL OXIDATIVE STRESS; SALEN-MANGANESE COMPLEXES; NORMAL TISSUE-INJURY; IONIZING-RADIATION; GENE-THERAPY; NITRIC-OXIDE; LUNG INJURY; ANGIOGENESIS; ANTIOXIDANTS; PROTECTION;
D O I：
10.1038/jid.2012.410
中图分类号：
R75 [皮肤病学与性病学];
学科分类号：
100206 ;
摘要：
In the event of a radionuclear attack or nuclear accident, the skin would be the first barrier exposed to radiation, though skin injury can progress over days to years following exposure. Chronic oxidative stress has been implicated as being a potential contributor to the progression of delayed radiation-induced injury to skin and other organs. To examine the causative role of oxidative stress in delayed radiation-induced skin injury, including impaired wound healing, we tested a synthetic superoxide dismutase (SOD)/catalase mimetic, EUK-207, in a rat model of combined skin irradiation and wound injury. Administered systemically, beginning 48 hours after irradiation, EUK-207 mitigated radiation dermatitis, suppressed indicators of tissue oxidative stress, and enhanced wound healing. Evaluation of gene expression in irradiated skin at 30 days after exposure revealed a significant upregulation of several key genes involved in detoxication of reactive oxygen and nitrogen species. This gene expression pattern was primarily reversed by EUK-207 therapy. These results demonstrate that oxidative stress has a critical role in the progression of radiation-induced skin injury, and that the injury can be mitigated by appropriate antioxidant compounds administered 48 hours after exposure. Journal of Investigative Dermatology (2013) 133, 1088-1096; doi:10.1038/jid.2012.410; published online 29 November 2012
引用
收藏
页码：1088 / 1096
页数：9
相关论文
共 52 条
  • [1] Sensitivity to Low-Dose/Low-LET Ionizing Radiation in Mammalian Cells Harboring Mutations in Succinate Dehydrogenase Subunit C is Governed by Mitochondria-Derived Reactive Oxygen Species
    Aykin-Burns, Nukhet
    Slane, Benjamin G.
    Liu, Annie T. Y.
    Owens, Kjerstin M.
    O'Malley, Malinda S.
    Smith, Brian J.
    Domann, Frederick E.
    Spitz, Douglas R.
    [J]. RADIATION RESEARCH, 2011, 175 (02) : 150 - 158
  • [2] Prevention of cognitive deficits and brain oxidative stress with superoxide dismutase/catalase mimetics in aged mice
    Clausen, Aaron
    Doctrow, Susan
    Baudry, Michel
    [J]. NEUROBIOLOGY OF AGING, 2010, 31 (03) : 425 - 433
  • [3] Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling
    Cox, Andrew G.
    Winterbourn, Christine C.
    Hampton, Mark B.
    [J]. BIOCHEMICAL JOURNAL, 2010, 425 : 313 - 325
  • [4] Novel mitochondria-targeted antioxidants, "Skulachev-Ion" derivatives, accelerate dermal wound healing in animals
    Demianenko, I. A.
    Vasilieva, T. V.
    Domnina, L. V.
    Dugina, V. B.
    Egorov, M. V.
    Ivanova, O. Y.
    Ilinskaya, O. P.
    Pletjushkina, O. Y.
    Popova, E. N.
    Sakharov, I. Y.
    Fedorov, A. V.
    Chernyak, B. V.
    [J]. BIOCHEMISTRY-MOSCOW, 2010, 75 (03) : 274 - 280
  • [5] Doctrow S R, 1997, Adv Pharmacol, V38, P247
  • [6] Doctrow S.R., 2005, MED INORGANIC CHEM, P319
  • [7] Salen-manganese complexes as catalytic scavengers of hydrogen peroxide and cytoprotective agents: structure-activity relationship studies
    Doctrow, SR
    Huffman, K
    Marcus, CB
    Tocco, G
    Malfroy, E
    Adinolfi, CA
    Kruk, H
    Baker, K
    Lazarowych, N
    Mascarenhas, J
    Malfroyt, B
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (20) : 4549 - 4558
  • [8] Doctrow SR, 2003, OXIDATIVE STRESS AGI, P1324
  • [9] Effects of MnSOD-plasmid liposome gene therapy on antioxidant levels in irradiated murine oral cavity orthotopic tumors
    Epperly, Michael W.
    Wegner, Rodney
    Kanai, Anthony J.
    Kagan, Valerian
    Greenberger, Emily E.
    Nie, Suhua
    Greenberger, Joel S.
    [J]. RADIATION RESEARCH, 2007, 167 (03) : 289 - 297
  • [10] GONZALEZ PK, 1995, J PHARMACOL EXP THER, V275, P798
123456