Fractional conversion of thromboxane B2 to urinary 11-dehydrothromboxane B2 in man

• Published in: Biochimica et biophysica acta Vol. 992; no. 1; pp. 66 - 70
• Main Authors: Ciabattoni, Giovanni, Pugliese, Francesco, Davi, Giovanni, Pierucci, Alessandro, Simonetti, Bianca M., Patrono, Carlo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 21.07.1989; North-Holland
• Subjects: Adult; Analysis of complex biological substances; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Blood and biological fluids; Chromatography, Liquid; Fundamental and applied biological sciences. Psychology; Humans; Male; Radioimmunoassay; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - blood; Thromboxane B2 - metabolism; Thromboxane B2 - urine; Assay; Human; Urine; Excretion; Hydration; Thromboxane B2; Oxidation; Metabolism
• ISSN: 0304-4165; 0006-3002
• DOI: 10.1016/0304-4165(89)90051-2

Thromboxane (TX) B2, the chemically stable hydration product of pro-aggregatory TXA2, undergoes two major pathways of metabolism in man, resulting in the formation of 2.3-dinor-TXB2 and 11-dehydro-TXB2, respectively. We have measured the excretion of the latter during the infusion of exogenous TXB2 over a 50-fold dose range in order to examine the fractional conversion of TXB2 to urinary 11-dehydro-TXB2 and to re-assess the rate of entry of endogenous TXB2 into the circulation. Four healthy male volunteers received 6-h intravenous infusions of the vehicle alone and TXB2 at 0.1, 1.0 and 5.0 ng.kg-1.min-1 in random order. They were pretreated with aspirin 325 mg/d in order to suppress endogenous TXB2 production. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured before, during and up to 24 h after the infusions and in aspirin-free periods, by means of NICI-GC/MS-validated radioimmunoassays. Aspirin treatment suppressed urinary 11-dehydro-TXB2 by 91%. The fractional elimination of 11-dehydro-TXB2 was independent of the rate of TXB2 infusion and averaged 6.8 +/- 0.7%, as compared to 6.4 +/- 0.9% for 2,3-dinor-TXB2. Interpolation of 11-dehydro-TXB2 values obtained in aspirin-free periods onto the linear relationship between the quantities of infused TXB2 and the amount of metabolite excreted in excess of control values (y = 0.0058x, r = 0.94, P less than 0.001) permitted calculation of the mean rate of entry of endogenous TXB2 into the circulation as 0.12 ng.kg-1.min-1. We conclude that: (a) urinary 11-dehydro-TXB2 is at least as abundant a conversion product of exogenously infused TXB2 as 2,3-dinor-TXB2; (b) its excretion increases linearly as a function of the rate of entry of TXB2 into the circulation up to approx. 40-fold the calculated rate of secretion of endogenous TXB2; (c) the latter is consistent with previous estimates based on monitoring of the beta-oxidation pathway of TXB2 metabolism.