Quinoid radio-toxin (QRT) induced metabolic changes in mice: an ex vivo and in vivo EPR investigation

Nitric Oxide. 2008 May;18(3):216-22. doi: 10.1016/j.niox.2008.01.002. Epub 2008 Jan 26.

Abstract

Radio-toxins are toxic metabolites produced by ionizing irradiation and have toxic effects similar to those caused by direct irradiation. We have investigated the effect of a quinoid radio-toxin (QRT) obtained from gamma-irradiated potato tuber on various organs in mice using ex vivo and in vivo EPR spectroscopy. Results indicate a decrease in the activity of ribonucleotide reductase enzyme in spleen of mice treated with 0.2mg QRT. A dose of 2mg QRT was fatal to mice within 45-60 min of treatment. Nitrosyl hemoglobin complexes alpha-(Fe(2+)-NO)alpha-(Fe(2+))beta-(Fe(2+))(2) were detected from spleen, blood, liver, kidney, heart, and lung tissue samples of mice treated with lethal doses of QRT. A significant decrease of pO(2) in liver and brain was observed after administration of QRT at the lethal dose. The time of the appearance of the nitrosyl hemoglobin complex and its intensity varied with the dose of QRT and the type of tissue. These results indicate that the effect of the QRT is more prominent in spleen and to a lesser extent in liver and blood. The QRT action at the lethal doses resulted in an increased hypoxia over time with disruption of compensatory adaptive response. The results indicate similar outcome of QRT as observed with gamma-irradiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Electron Spin Resonance Spectroscopy / methods
  • Enzyme Activation / drug effects
  • Gamma Rays
  • Heart / drug effects
  • Hemoglobins / biosynthesis
  • Injections, Intraperitoneal
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oxygen / antagonists & inhibitors
  • Oxygen / metabolism
  • Plant Tubers / chemistry
  • Plant Tubers / radiation effects
  • Quinones / isolation & purification
  • Quinones / toxicity*
  • Ribonucleotide Reductases / antagonists & inhibitors*
  • Ribonucleotide Reductases / metabolism
  • Solanum tuberosum / chemistry
  • Solanum tuberosum / radiation effects
  • Spleen / drug effects*
  • Spleen / enzymology
  • Spleen / metabolism*
  • Time Factors
  • Toxins, Biological / isolation & purification
  • Toxins, Biological / toxicity*

Substances

  • Hemoglobins
  • Quinones
  • Toxins, Biological
  • nitrosyl hemoglobin
  • Ribonucleotide Reductases
  • Oxygen