S-(2-hydroxy-3-buten-1-yl)glutathione and S-(1-hydroxy-3-buten-2-yl)glutathione are in vivo metabolites of butadiene monoxide: detection and quantitation in bile.
Administration (ip) of butadiene monoxide, a toxic metabolite of 1,3-butadiene, to rats caused the appearance of two new biliary peaks when analyzed by HPLC chromatography. These peaks were isolated and identified as the regioisomeric glutathione conjugates, S-(2-hydroxy-3-buten-1-yl)glutathione (I) and S-(1-hydroxy-3-buten-2-yl)glutathione (II), by comparison of their HPLC retention times and fast atom bombardment mass spectra to those of synthetic standards. S-(4-Hydroxy-2-buten-1-yl)glutathione, a rearrangement product formed during chemical synthesis or storage of I, was not detected. Whether butadiene monoxide was given at a dose of 14.3 or 143 mumol/kg, the amount of conjugates excreted in 30 min was at least 85% of that excreted in 120 min. Conjugate excretion in 60 min did not exhibit saturation when the butadiene monoxide dose was varied between 14.3 and 286 mumol/kg; the total amount of the butadiene monoxide dose excreted as combined I and II averaged only 7.6 +/- 4.2% (mean +/- SD, n = 12), with approximately a 3:1 ratio of isomers I:II being excreted at all butadiene monoxide doses. Whereas these results indicate a role for glutathione S-transferase-catalyzed reactions in butadiene monoxide metabolism in vivo, biliary excretion of I and II can only account for a small fraction of the butadiene monoxide dose given.
Sharer
J E
JE
Department of Comparative Biosciences, University of Wisconsin, Madison 53706.
Elfarra
A A
AA
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004852:Epoxy Compounds / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D016339:Spectrometry, Mass, Fast Atom Bombardment
D004852:Epoxy Compounds; C079490:S-(2-hydroxy-3-buten-1-yl)glutathione; C079491:S-(1-hydroxy-3-buten-2-yl)glutathione; C024370:3,4-epoxy-1-butene; D005978:Glutathione