title: Nicaraven attenuates radiation-induced injury in hematopoietic stem/progenitor cells in mice.
abstract: Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been demonstrated to protect against ischemia-reperfusion injury in various organs. We investigated whether nicaraven can attenuate radiation-induced injury in hematopoietic stem/progenitor cells, which is the conmen complication of radiotherapy and one of the major causes of death in sub-acute phase after accidental exposure to high dose radiation. C57BL/6 mice were exposed to 1 Gy γ-ray radiation daily for 5 days in succession (a total of 5 Gy), and given nicaraven or a placebo after each exposure. The mice were sacrificed 2 days after the last radiation treatment, and the protective effects and relevant mechanisms of nicaraven in hematopoietic stem/progenitor cells with radiation-induced damage were investigated by ex vivo examination. We found that post-radiation administration of nicaraven significantly increased the number, improved the colony-forming capacity, and decreased the DNA damage of hematopoietic stem/progenitor cells. The urinary levels of 8-oxo-2'-deoxyguanosine, a marker of DNA oxidation, were significantly lower in mice that were given nicaraven compared with those that received a placebo treatment, although the levels of intracellular and mitochondrial reactive oxygen species in the bone marrow cells did not differ significantly between the two groups. Interestingly, compared with the placebo treatment, the administration of nicaraven significantly decreased the levels of the inflammatory cytokines IL-6 and TNF-α in the plasma of mice. Our data suggest that nicaraven effectively diminished the effects of radiation-induced injury in hematopoietic stem/progenitor cells, which is likely associated with the anti-oxidative and anti-inflammatory properties of this compound.
authors.affiliation: Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kawakatsu
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Urata
authors.forename: Ryo
authors.initials: R
authors.lastname: Imai
authors.forename: Shinji
authors.initials: S
authors.lastname: Goto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ono
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nishida
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D005720:Gamma Rays / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009536:Niacinamide / Q000031:analogs & derivatives; D011832:Radiation Injuries / Q000097:blood / Q000188:drug therapy / Q000652:urine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C042625:nicaraven
references.citation: Surgery. 2011 Jun;149(6):792-800
references.pmid: 21507448
references.citation: J Clin Oncol. 2003 Jul 1;21(13):2545-50
references.pmid: 12829674
references.citation: Neurol Res. 1984 Mar-Jun;6(1-2):49-53
references.pmid: 6147779
references.citation: Cytokine. 2012 May;58(2):169-77
references.pmid: 22277799
references.citation: Chem Pharm Bull (Tokyo). 2000 Apr;48(4):467-76
references.pmid: 10783063
references.citation: Neurol Res. 1984 Dec;6(4):163-8
references.pmid: 6152308
references.citation: Oncogene. 2003 Sep 1;22(37):5848-54
references.pmid: 12947391
references.citation: Shock. 2000 Feb;13(2):126-34
references.pmid: 10670842
references.citation: Free Radic Res. 2012 Feb;46(2):147-53
references.pmid: 22126415
references.citation: Int J Radiat Biol. 2009;85(10):837-50
references.pmid: 19863200
references.citation: J Clin Oncol. 2011 Jun 20;29(18):2590-7
references.pmid: 21576630
references.citation: Carcinogenesis. 2003 May;24(5):919-25
references.pmid: 12771037
references.citation: J Neurosurg. 1996 May;84(5):792-803
references.pmid: 8622153
references.citation: Curr Med Chem. 2009;16(2):130-43
references.pmid: 19149566
references.citation: Surgery. 2000 Jun;127(6):661-9
references.pmid: 10840362
references.citation: PLoS One. 2011;6(12):e29399
references.pmid: 22216271
references.citation: Life Sci. 2000 Jan 21;66(9):779-90
references.pmid: 10698353
references.citation: J Clin Oncol. 2005 Aug 20;23(24):5805-13
references.pmid: 16027437
references.citation: Transplant Proc. 1998 Nov;30(7):3758-60
references.pmid: 9838646
references.citation: Free Radic Biol Med. 2011 Jul 1;51(1):30-7
references.pmid: 21565268
references.citation: Mol Cell Biochem. 1998 Jan;178(1-2):237-43
references.pmid: 9546605
references.citation: PLoS One. 2011;6(10):e25543
references.pmid: 21984919
references.citation: Neurosci Res. 1995 Sep;23(2):217-21
references.pmid: 8532218
references.citation: Radiat Res. 2012 Mar;177(3):244-50
references.pmid: 22149991
references.citation: Free Radic Biol Med. 2010 Jan 15;48(2):348-56
references.pmid: 19925862
references.citation: J Neurosurg. 2000 Jun;92(6):1009-15
references.pmid: 10839263
references.citation: Int J Radiat Biol. 2004 Apr;80(4):251-9
references.pmid: 15204702
references.citation: PLoS One. 2010 Feb 01;5(2):e8980
references.pmid: 20126546
references.citation: Nihon Igaku Hoshasen Gakkai Zasshi. 1993 Jun 25;53(6):704-12
references.pmid: 8337113
references.citation: Int J Radiat Biol. 2009 Mar;85(3):177-95
references.pmid: 19296341
references.citation: Anticancer Res. 2006 Sep-Oct;26(5A):3421-7
references.pmid: 17094462
references.citation: Stem Cells. 2010 Jul;28(7):1178-85
references.pmid: 20506176
references.citation: Blood. 2011 Dec 15;118(25):6572-9
references.pmid: 22039262