title: Gamma-tocopherol-N,N-dimethylglycine ester as a potent post-irradiation mitigator against whole body X-irradiation-induced bone marrow death in mice.
abstract: We examined the radioprotective and mitigative effects of gamma-tocopherol-N,N-dimethylglycine ester (GTDMG), a novel water-soluble gamma-tocopherol derivative, against X-irradiation-induced bone marrow death in mice. Mice (C3H, 10 weeks, male) were injected intraperitoneally with GTDMG suspended in a 0.5% methyl cellulose solution before or after receiving of 7.5-Gy whole body X-irradiation. GTDMG significantly enhanced the 30-day survival rate when given 30 min before or immediately after the irradiation. Its mitigative activity (administered after exposure) was examined further in detail. The optimal concentration of GTDMG given immediately after irradiation was around 100 mg/kg body weight (bw) and the 30-day survival rate was 97.6 ± 2.4%. When GTDMG was administered 1, 10 and 24 h post-irradiation, the survival rate was 85.7 ± 7.6, 75.0 ± 9.7 and 36.7 ± 8.8%, respectively, showing significant mitigation even at 24 h after irradiation (P < 0.05). The value of the dose reduction factor (100 mg/kg bw, given intraperitoneally (i.p.) immediately after irradiation) was 1.25. GTDMG enhanced the recovery of red blood cell-, white blood cell-, and platelet-counts after irradiation and significantly increased the number of endogenous spleen colonies (P < 0.05). Subcutaneous (s.c.) administration also had mitigative effects. In conclusion, GTDMG is a potent radiation mitigator.
authors.affiliation: Nihon Pharmaceutical University.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Anzai
authors.forename: Megumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ikota
authors.forename: Jiro
authors.initials: J
authors.lastname: Takata
mesh_terms: D000818:Animals; D001855:Bone Marrow Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051379:Mice; D008809:Mice, Inbred C3H; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D024504:gamma-Tocopherol / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D011837:Radiation-Protective Agents; C512054:gamma-tocopherol-N,N-dimethylglycinate hydrochloride; D024504:gamma-Tocopherol; D005998:Glycine
keywords: X-ray; bone marrow death; radiation mitigator; vitamin E analog; whole body irradiation
references.citation: Life Sci. 2000 Apr 7;66(20):1905-13
references.pmid: 10821115
references.citation: J Lipid Res. 2002 Dec;43(12):2196-204
references.pmid: 12454283
references.citation: Radiology. 1980 Sep;136(3):763-6
references.pmid: 7403557
references.citation: Radiat Res. 2011 Jun;175(6):736-45
references.pmid: 21434782
references.citation: Curr Probl Cancer. 2001 Nov-Dec;25(6):334-411
references.pmid: 11740469
references.citation: J Clin Biochem Nutr. 2012 Jan;50(1):2-8
references.pmid: 22247595
references.citation: J Radiat Res. 1994 Sep;35(3):147-56
references.pmid: 7830258
references.citation: Exp Mol Pathol. 2006 Aug;81(1):55-61
references.pmid: 16426603
references.citation: Int J Radiat Biol. 2009 Jul;85(7):539-73
references.pmid: 19557599
references.citation: Br J Radiol. 2012 Nov;85(1019):e1093-103
references.pmid: 22674714
references.citation: Radiat Res. 2009 Oct;172(4):519-24
references.pmid: 19772473
references.citation: Experientia. 1978 Sep 15;34(9):1216-7
references.pmid: 720531
references.citation: Int J Radiat Oncol Biol Phys. 1992;23(4):841-5
references.pmid: 1319980
references.citation: Radiat Res. 2012 May;177(5):628-42
references.pmid: 22175300
references.citation: Br J Radiol. 1973 Jul;46(547):538-40
references.pmid: 4718295
references.citation: Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):884-91
references.pmid: 20950957
references.citation: Ann Surg. 1995 Oct;222(4):504-8; discussion 508-10
references.pmid: 7574930
references.citation: Int J Radiat Biol. 2011 Oct;87(10):1052-60
references.pmid: 21728759
references.citation: Strahlenther Onkol. 1986 Jun;162(6):391-9
references.pmid: 3526601
references.citation: Science. 2008 Apr 11;320(5873):226-30
references.pmid: 18403709
references.citation: Int J Radiat Biol. 1993 Jun;63(6):759-64
references.pmid: 8100263
references.citation: Radiat Res. 2011 Jun;175(6):746-58
references.pmid: 21476857
references.citation: Cancer Res. 1981 Jul;41(7):2954-8
references.pmid: 7018674
references.citation: Radiat Res. 2004 Feb;161(2):161-7
references.pmid: 14731074
references.citation: Int J Radiat Biol. 2009 Jul;85(7):598-606
references.pmid: 19557601
references.citation: Radiat Res. 2011 Mar;175(3):297-306
references.pmid: 21388273
references.citation: J Radiat Res. 2008 Jul;49(4):425-30
references.pmid: 18480592
references.citation: Radiat Res. 2003 Dec;160(6):655-61
references.pmid: 14640781
references.citation: Radiat Res. 2011 Jun;175(6):728-35
references.pmid: 21529145
references.citation: Radiat Res. 1991 Mar;125(3):293-7
references.pmid: 2000453
references.citation: Mutat Res. 1993 Feb;301(2):143-7
references.pmid: 7678172
references.citation: J Radiat Res. 2013 Mar 1;54(2):210-20
references.pmid: 23038797
references.citation: Pharmacol Ther. 1988;39(1-3):393-5
references.pmid: 3200896
references.citation: Biochim Biophys Acta. 2013 Jan;1831(1):117-25
references.pmid: 23127512
references.citation: Radiat Res. 2009 Jun;171(6):698-707
references.pmid: 19580476
references.citation: Science. 2004 Apr 30;304(5671):693-4
references.pmid: 15118152
references.citation: Int Immunopharmacol. 2012 Dec;14(4):495-503
references.pmid: 23000517
references.citation: Nihon Igaku Hoshasen Gakkai Zasshi. 1986 Nov 25;46(11):1324-30
references.pmid: 3547316
references.citation: J Radiat Res. 2001 Mar;42(1):21-37
references.pmid: 11393887