Urinary excretion of 2,3-dinor-thromboxane B1, a major metabolite of thromboxane B2 in the rat.
Urinary 2,3-dinor-thromboxane B2 (2,3-dinor-TXB2), an enzymatic degradation product of TXB2, is currently measured for evaluating in vivo thromboxane biosynthesis in rats. We simultaneously measured 2,3-dinor-TXB2 and 2,3-dinor-TXB1, another product of TXB2 metabolism, in the urine of rats by immunoaffinity extraction/gas chromatography negative ion chemical ionization mass spectrometry (GC-NICIMS). In rats under basal conditions, urinary excretion of 2,3-dinor-TXB1 was much higher than that of 2,3-dinor-TXB2 (19.22 +/- 4.86 and 1.64 +/- 0.29 ng/24 h, respectively). The relative abundance of the two metabolites in each animal was fairly constant (91.9 +/- 1.6 and 8.1 +/- 1.6% of their sum, respectively). Urinary excretion of both 2,3-dinor-TXB1 and 2,3-dinor-TXB2 increased in rats undergoing in vivo hepatic ischemia-reperfusion. Other thromboxane metabolites, including 11-dehydro-TXB2 and 11-dehydro-2,3-dinor-TXB2, were measured by GC-NICIMS in selected urines. The resulting profile was: 2,3,4,5-tetranor-TXB1 > 2,3-dinor-TXB1 >> 11-dehydro-TXB2 > 2,3-dinor-TXB2 = TXB2. This study shows that urinary 2,3-dinor-TXB1 is a suitable parameter of TXB2 biosynthesis in vivo in rats. The possible cross-reactivity of 2,3-dinor-TXB1 in immunoassays of urinary 2,3-dinor-TXB2 or even TXB2 in rats should be considered in future studies.
Chiabrando
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C
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Corada
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M
Bachi
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Fanelli
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R
D000818:Animals; D007511:Ischemia; D008099:Liver / Q000098:blood supply; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D013931:Thromboxanes / Q000031:analogs & derivatives*
C089758:2,3,4,5-tetranorthromboxane B1; C089757:2,3-dinorthromboxane B1; D013931:Thromboxanes; C081960:11-dehydro-2,3-dinor-thromboxane B2; D013929:Thromboxane B2; C028965:2,3-dinor-thromboxane B2; C049235:11-dehydro-thromboxane B2