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.
Subject(s)
Quinones/toxicity , Ribonucleotide Reductases/antagonists & inhibitors , Spleen/drug effects , Spleen/metabolism , Toxins, Biological/toxicity , 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 , Ribonucleotide Reductases/metabolism , Solanum tuberosum/chemistry , Solanum tuberosum/radiation effects , Spleen/enzymology , Time Factors , Toxins, Biological/isolation & purificationABSTRACT
The effect of radiotoxins (RT), obtained from gamma-irradiated potato tubers, on mice have been investigated using ex vivo EPR. Parts of liver, lung, spleen, heart and kidney were used for investigation. The amount of the preparations injected was 0.2 ml, RT concentration varying from 0.1 to 1 LD100 (LD100 = 100 mg/kg). An intraperitoneal injection of RT in dose of 0.1 LD100 resulted in metabolic changes only in spleen. During 8 hours after injection a gradual depression of enzyme ribonucleotide reductase activity in spleen has been observed. After the treatment of mice with a lethal dose of RT signals from nitrosyl complexes have been appeared in spectra from all tissue investigated. The intensities of lines depend both on a time passed after treatment and a sensitivity of tissue to RT action. One of the main reasons of the lethal outcome of mice treated with RT may be the breaking of the compensatory adaptive response due to enhanced hypoxic state resulting from the high concentration of nitrosyl complexes generated in the tissue.
Subject(s)
Electron Spin Resonance Spectroscopy/methods , Radioisotopes/toxicity , Animals , Heart/radiation effects , Kidney/metabolism , Kidney/radiation effects , Liver/metabolism , Liver/radiation effects , Lung/metabolism , Lung/radiation effects , Mice , Ribonucleotide Reductases/metabolism , Spleen/enzymology , Spleen/metabolism , Spleen/radiation effectsABSTRACT
The effect of radiotoxin (RT) obtained from y-irradiated potato tubes on blood of sheep and mice has been investigated by using in vitro and ex vivo EPR. In experiments in vitro, the action of different preparations (RT, extract from unirradiated potato tubers, 1%-HCl or 30%-hydrogen peroxide) on sheep blood has been compared. It has been established that RT is an effective oxidant (like 1%-HCl) of haem iron that leads to an increase of the methemoglobin concentration. The specific peculiarity of RT effect on blood in vitro is an appearance of two well-resolved lines from methemoglobin belonging, probably, to different paramagnetic centers. The signal from nonspecific complexes of Fe3+ has been also observed. Ex vivo EPR spectra markedly differ from these obtained in experiments in vitro. An additional line with g approximately 2.005 and width 6 G in 30 minutes after intraperitoneal RT injection in the lethal dose (0.2 ml of preparation containing of 2 mg RT) has been revealed. Subsequent intoxication of mice is accompanied by the appearance of the signal from nitrosyl complexes in EPR spectra. These differences in experimental results of in vitro and ex vivo EPR can be explained by launch of compensatory adaptive response of organism on the action of highly toxic preparation.
