Novel approach to in vivo screening for radioprotective activity in whole mice: in vivo electron spin resonance study probing the redox reaction of nitroxyl.
Previously, we reported that X-irradiation enhanced the signal decay of a spin probe injected into whole mice measured by in vivo ESR, and that the observed enhancement was suppressed by the pre-administration of cysteamine, a radioprotector [Miura, Y., Anzai, K., Urano, S. and Ozawa, T. (1997) Free Rad. Biol. Med. 23: 533-540]. In the present study, the suppression activity of the X-ray-induced increase in the ESR signal decay rate (termed suppression index, SI) was measured for several radioprotectors: 5-hydroxytryptamine (5-HT), S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721), 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (TEMPOL), cimetidine, interleukin-1 beta (IL-1 beta) and stem cell factor (SCF). The enhancement of the ESR signal decay of carbamoyl-PROXYL due to X-irradiation was suppressed by a treatment with all of the radioprotectors examined, showing positive SI values. However, a dose-dependency of 5-HT or WR-2721 was not observed, suggesting that several mechanisms exist for radioprotection and a modification of the signal decay rate. Although the in vivo ESR system cannot be used in place of the 30-day survival method for the assessment of radioprotectors, this system might be applicable to in vivo, non-invasive screening prior to using the 30-day survival method.
Miura
Y
Y
Department of Bioregulation Research, National Institute of Radiological Sciences, Chiba-shi, Japan.
Anzai
K
K
Ueda
J
J
Ozawa
T
T
D004999:Amifostine / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000032:analysis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D009589:Nitrogen Oxides / Q000032:analysis*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011759:Pyrrolidines / Q000032:analysis*; D011837:Radiation-Protective Agents / Q000032:analysis / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013113:Spin Labels; D019089:Stem Cell Factor / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology; D014916:Whole-Body Irradiation
D002839:Chromans; D003497:Cyclic N-Oxides; D007375:Interleukin-1; D009589:Nitrogen Oxides; D011759:Pyrrolidines; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D013113:Spin Labels; D019089:Stem Cell Factor; D014810:Vitamin E; D012701:Serotonin; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl; C066638:potassium ascorbyl tocopheryl phosphate; D002927:Cimetidine; C039900:nitroxyl; D004999:Amifostine; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C001803:tempol