Details

Autor(en) / Beteiligte

• Krause, R J
• Sharer, J E
• Elfarra, A A

Titel

Epoxide hydrolase-dependent metabolism of butadiene monoxide to 3-butene-1,2-diol in mouse, rat, and human liver

Ist Teil von

• Drug metabolism and disposition, 1997-08, Vol.25 (8), p.1013

Ort / Verlag

United States

Erscheinungsjahr

1997

Quelle

MEDLINE

Beschreibungen/Notizen

• Incubations of butadiene monoxide (BMO) with mouse, rat, and human liver microsomes or cDNA-expressed human microsomal epoxide hydrolase led to 3-buten-1,2-diol (BDD) detection; the BDD peak exhibited a GC/MS fragmentation pattern similar to that of reference material. Incubations with rat liver cytosol did not lead to BDD detection; however, when mouse or human liver cytosol was used, BDD was detected but at levels lower than those detected with the liver microsomes. The catalytic efficiency (V(max)/K(m) ratio) of BDD formation in rat liver microsomes was nearly 3-fold higher than the ratio obtained with mouse liver microsomes. Among two human liver microsomal samples, one sample exhibited a ratio that was nearly 3-fold higher than that of rat liver microsomes, and the second sample exhibited a ratio that was similar to that of rat liver microsomes. Although these results suggest epoxide hydrolases may play a role in BMO metabolism in vivo, rats and mice given BMO (71.3-285 micromol/kg) excreted <1% of the dose as BDD into urine within 24 hr. Thus, further studies into the role of epoxide hydrolases in BMO metabolism and disposition and the fate of BDD are warranted.