In vivo monitoring of hydroxyl radical generation caused by x-ray irradiation of rats using the spin trapping/EPR technique

Free Radic Biol Med. 2004 May 1;36(9):1134-43. doi: 10.1016/j.freeradbiomed.2004.02.016.

Abstract

Measurement of hydroxyl radical (*OH) in living animals irradiated with ionizing radiation should be required to clarify the mechanisms of radiation injury and the in vivo assessment of radiation protectors, because generation of *OH is believed to be one of the major triggers of radiation injury. In this study, *OH generation was monitored by spin trapping the secondary methyl radical formed by the reaction of *OH with dimethyl sulfoxide (DMSO). Rats were injected intraperitoneally with a DMSO solution of alpha-phenyl-N-tert-butylnitrone (PBN). X-irradiation of the rats remarkedly increased the six-line EPR signal in the bile. The strengthened signal was detectable above 40 Gy. Use of 13C-substituted DMSO revealed that the signal included the methyl radical adduct of PBN as a major component. The EPR signal of the PBN-methyl radical adduct was completely suppressed by preadministration of methyl gallate, a scavenger of *OH but not of methyl radical. Methyl gallate did not reduce the spin adducts to EPR-silent forms. These observations indicate that what we were measuring was *OH generated in vivo by x-irradiation. This is the first report of the in vivo monitoring of *OH generation at a radiation dose close to what people might receive in the case of radiological accident or radiation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / chemistry
  • Cyclic N-Oxides
  • Dimethyl Sulfoxide / chemistry
  • Dimethyl Sulfoxide / pharmacology
  • Dose-Response Relationship, Radiation
  • Electron Spin Resonance Spectroscopy*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / chemistry
  • Gallic Acid / pharmacology
  • Hydroxyl Radical / analysis*
  • Hydroxyl Radical / metabolism
  • Male
  • Nitrogen Oxides / chemistry
  • Rats
  • Spin Trapping / methods*
  • X-Rays*

Substances

  • Cyclic N-Oxides
  • Free Radical Scavengers
  • Nitrogen Oxides
  • Hydroxyl Radical
  • phenyl-N-tert-butylnitrone
  • methyl gallate
  • Gallic Acid
  • Dimethyl Sulfoxide