Liver slices in dynamic organ culture. I. An alternative in vitro technique for the study of rat hepatic drug metabolism.
1. Precision-cut liver slices in dynamic organ culture, a novel in vitro technique, is described and applied to the study of hepatic drug metabolism in the rat. 2. These slices catalysed the oxidative O-deethylation of the substrate, 7-ethoxycoumarin, over 6 h incubation. In addition, the direct conjugation of 7-hydroxycoumarin with either sulphate or glucuronic acid was maintained over 6 h. 3. The formation of 7-hydroxycoumarin and the presence of the sulphate and glucuronide conjugates in slices exposed to 7-ethoxycoumarin demonstrated integrated phase I and phase II drug metabolizing activities in this system. 4. Minor modifications of the incubation system allowed for the metabolism of four volatile chlorinated benzenes: monochlorobenzene 1,2-, 1,3-, and 1,4-dichlorobenzenes to aqueous soluble metabolites. 5. The use of liver slices in dynamic organ culture as an alternative preparation for the study of xenobiotic metabolism is discussed.
Barr
J
J
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721.
Weir
A J
AJ
Brendel
K
K
Sipes
I G
IG
D000818:Animals; D002021:Buffers; D002722:Chlorobenzenes / Q000378:metabolism; D003374:Coumarins / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014468:Umbelliferones / Q000378:metabolism
D002021:Buffers; D002722:Chlorobenzenes; D003374:Coumarins; D004364:Pharmaceutical Preparations; D014468:Umbelliferones; C017299:7-ethoxycoumarin; C031477:7-hydroxycoumarin; C004726:2-dichlorobenzene; C042146:1,3-dichlorobenzene; C018511:4-dichlorobenzene