EFFECTS OF BETA-AMINOETHYLISOTHIOUREA (AET) ON ENZYMES OF ANIMAL TISSUES
Technical Report
·
OSTI ID:4256144
The effects of the radioprotective compound aminoethylisothiourea (AET) on sulfhydryl enzymes of mammaliand tissues have been detemained, in and effort to obtain information regarding the biologic activity of the drug. A number of enzyme systems involved in oxi-dative carbohydrate metabolism of rat tissues were inhibited in vitro by concentrations of AET within the predicted in vivo randge following sublethal doses. Two of these enzyme systems, the pyruvic and alpha-ketoglutaric acid oxidizing systems of rat liver and kidney, were also markedly inhibited in vivo by AET. Inhibition was not due to and effect on coenzymes involved in the reactions but may have been caused by inactivation of the electron transport system. The time of onset of enzyme inhibition and the rate of reversal were in agreement with the onset and severity of axic mandifestations in the rat following AET administration and, furthermore, were correlated with the time of maximum radioprotection. However, a study of the susceptibility of several liver enzymes in different species failed to establish a relationship between either the toxicity or the radioprotective activity of AET and the degree of sulfhydryl enzyme inhibition. AET also stimulated anaerobic glycolysis in rat liver slices and produced lactacidemia in rats after parenteral administration. Efforts a locate the enzymatic site of the glycolytic action were not successful. The results of this study demonstrate the feasibility of a theory of radioprotective mechanisms involving the formation of radioresistant complexes between the protective agent and important biologic sulfhydryl groups. (auth)
- Research Organization:
- Chicago. Univ. Air Force Radiation Lab.
- NSA Number:
- NSA-13-018800
- OSTI ID:
- 4256144
- Report Number(s):
- AF-SAM-59-34
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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