Thromboxane-mediated injury following radiation. Annual summery report, 15 January-1 September 1984
The hypothesis under investigation is that moderate levels of radiation exposure result in endothelial and other tissue damage which, in turn, increases in vivo synthesis of thromboxane A2 (TXA2) and/or decreases synthesis of prostacyclin (PGI2). It is proposed that this altered arachidonate metabolism results in vasoconstriction and decreased peripheral blood flow, thereby leading to further tissue damage which is proportional to the degree of radiation exposure. The observations described in this first annual report demonstrate that the whole-body gamma irradiation results in an indomethacin-sensitive increase in urine TXB2 four to 120 hours after 10 Gy and four to 12 hours after 20 Gy whole-body irradiation. These studies also showed that radiation-induced increases in TXB2 are due to altered extrarenal synthesis, while the altered 6-keto PGFla levels appear to be due to changes in intrarenal arachidonate metabolism. A systematic evaluation of the role of the kidney in elaborating altered urine arachidonate metabolite levels will be conducted using the isolated perfused rat kidney preparation. The role that free radicals play in altered cyclooxygenase product synthesis will be determined by using free-radical scavengers after irradiation, and by the use of hydrogen peroxide injections to simulate radiation-induced peroxide formation in non-irradiated rats. Finally, the effect of ionizing radiation and the observed alterations of arachidonate metabolism on vascular reactivity will be assessed in order to determine the degree to which cyclooxygenase pathway products play a role in the pathogenesis of acute radiation injury.
- Research Organization:
- Georgetown Univ., Washington, DC (USA). Dept. of Physiology and Biophysics
- OSTI ID:
- 5584599
- Report Number(s):
- AD-A-165043/1/XAB
- Country of Publication:
- United States
- Language:
- English
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Thromboxane-mediated injury following radiation. Annual report, 1 September 1984-31 August 1985
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANALGESICS
ANIMAL TISSUES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL WASTES
BLOOD CIRCULATION
BODY
BODY FLUIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DAMAGE
DRUGS
ENDOTHELIUM
ENZYMES
EXTERNAL IRRADIATION
INJURIES
IRRADIATION
KIDNEYS
KINETICS
MAMMALS
MATERIALS
METABOLISM
METABOLITES
ORGANS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PATHOGENESIS
PEROXIDES
RADIATION EFFECTS
RADIATION INJURIES
RATS
REACTION KINETICS
RODENTS
SYNTHESIS
TISSUES
URINE
VERTEBRATES
WASTES
WHOLE-BODY IRRADIATION