Impact of warm ischemic time on microsomal P450 isoforms in a porcine model of therapeutic liver resection.
Human microsomes and hepatocytes obtained from non-transplantable livers of brain-dead donors are very useful in predicting the in vivo metabolism of xenobiotics in humans. Fresh liver specimens obtained from therapeutic liver resection are also useful for research in cases where non-transplantable livers are not readily available. In the present study, the effect of warm ischemic duration, in the course of hepatic surgery, on the activities of liver cytochrome P450 (CYP) CYP1A, CYP2C, CYP2D, CYP2E1 and CYP3A were evaluated in a porcine model. Partial occlusion (portal vein and hepatic artery occlusion) decreased the activities of CYP2C, CYP2E and CYP3A, but not those of CYP1A and CYP2D. CYP3A, known to account for an average 30% of total P450 content in the human liver was the most susceptible to the warm ischemia. These results demonstrate that the activities of CYP isoforms, particularly those of CYP3A, are markedly affected by warm ischemia; it is, therefore, essential that care should be exercised when using microsomes prepared from surgically removed livers.
Suzuki
Satoshi
S
Research Laboratories, HAB Research Organization, Cornea Center Bldg. 3rd Floor, Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8523, Japan. suzuki@hab.or.jp
Satoh
Tetsuo
T
Yoshino
Hiroyuki
H
Kobayashi
Eiji
E
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006358:Hot Temperature; D015151:Immunoblotting; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000601:surgery; D008862:Microsomes, Liver / Q000378:metabolism*; D023421:Models, Animal; D034421:Sus scrofa
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System