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Title: The role of peroxides as modulators of human blood platelet function

Conference · · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)
OSTI ID:5481814
;  [1]
  1. Medical College of Virginia, Richmond (United States)

The ability to peroxidize lipid in the vicinity of arterial walls has been demonstrated through oxidation of the LDL-particle by monocytes/macrophages, smooth muscle cells, and endothelial cells. The authors questioned what effect increased levels of peroxides might have on platelet function. Platelet aggregation, studied trubidometrically, was initiated by arachidonic acid (AA) alone or in the presence of a low concentration of H{sub 2}O{sub 2}, (which by itself could not initiate aggregation). Aggregation was analyzed quantitatively by measuring the time it took to reach 1/2 the maximal extent of aggregation (T1/2Max). Using the minimal concentration of AA still able to initiate aggregation (0.2-0.45 mM) the T1/2Max was 112{+-}35 (n=10). With 50% of the respective AA conc. plus 17 {mu}M H{sub 2}O{sub 2}, the T1/2Max was 52{+-}21. Under similar circumstances, the amount of AA able to initiate aggregation could be reduced by 80% with the addition of H{sub 2}O{sub 2}. These effects could be duplicated by glucose oxidase, 0.015-0.15 IU, and could be eliminated by the addition of catalase (<25 U/ml) at any time prior to the start of aggregation. With non-aggregating concentrations of AA alone, synthesis of Thromboxane B{sub 2} was negligible; with aggregation by the same AA plus H{sub 2}O{sub 2} it was 550{+-}79 pg/10{sup 3} platelets. Both aggregation and TxB{sub 2} synthesis were completely inhibited by aspirin or indomethacin, and by the antioxidants phenol and nor-dihydroguaretic acid, at concentrations known to inhibit cyclooxygenase. In platelets with a defect in the second wave of ADP induced aggregation, but having normal aggregation with added AA (indicating the cyclooxygenase-thromboxane axis was intact), sub-aggregating concentrations of AA, plus H{sub 2}O{sub 2} resulted in brisk aggregation.

OSTI ID:
5481814
Report Number(s):
CONF-9004153-; CODEN: FAJOE
Journal Information:
FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 4:3; Conference: 74. annual meeting of the Federation of American Societies for Experimental Biology, Washington, DC (United States), 1-5 Apr 1990; ISSN 0892-6638
Country of Publication:
United States
Language:
English