Induction of cytochrome P450 2B1-mRNA and pentoxyresorufin O-depentylation after exposure of precision-cut rat liver slices to phenobarbital.
Precision-cut rat liver slices were prepared from male Wistar rats with a Krumdieck slicer and cultured in William's medium E for up to 24 h. In untreated control slices, CYP2B1-mRNA concentration, which was quantified by competitive RT-PCR, did not decrease during this time. After exposure of the slices to 100 microM phenobarbital, CYP2B1-mRNA increased by about 10- or 60-fold after 6 or 24 h, respectively. The extent of this in vitro induction was similar to that after in vivo administration of 60 mg/kg phenobarbital. Pentoxyresorufin O-depentylation (PROD) was also inducible in vitro after 24 h, but to a lesser extent than the corresponding CYP-mRNA. Precision-cut liver slices proved to be a simple and reliable in vitro system for the sensitive detection of an induction by phenobarbital.
Müller
D
D
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Klinikum der FSU Jena, 07740, Jena, Germany. dmue@mti-n.uni-jena.de
Steinmetzer
P
P
Pissowotzki
K
K
Glöckner
R
R
D000818:Animals; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008867:Microtomy; D010634:Phenobarbital / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006993:Hypnotics and Sedatives; D012333:RNA, Messenger; D019362:Cytochrome P-450 CYP2B1; D010634:Phenobarbital