Thromboxane-Mediated Injury Following Radiation.
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 31, 1984
- Accession Number
- ADA165043
Entities
People
- John C. Rose
Organizations
- Georgetown University