Precision-cut liver slices from rats of different ages: basal cytochrome P450-dependent monooxygenase activities and inducibility.
The biotransformation capacity - of the cytochrome P450 (CYP) system for example - is lower but inducibility is more pronounced in neonates than in adults. On the other hand, both enzyme activities and inducibility decline with senescence. Precision-cut rat liver slices are widely used as an in vitro tool for the examination of drug toxicity, xenobiotic metabolism or enzyme induction. The aim of the present study was to assess whether age-related changes in CYP activities and induction observed in vivo are also mirrored in vitro in liver slices. For this purpose, different CYP model reactions were measured in precision-cut liver slices from one-day-old, 40-day-old and one-year-old rats after in vitro exposure to various inducers. Similar to the in vivo situation, basal CYP activities were distinctly lower and inducibility was much more pronounced in liver slices from neonatal than in those from adult animals. Also, enzyme activities were mostly somewhat lower in liver slices from aged rats compared to those from 40-day-old rats. However, CYP inducibility was less pronounced than with younger animals too. Thus, precision-cut rat liver slices are a suitable in vitro tool for investigating age-related changes in CYP activities and induction as well as developmental differences in drug metabolism and toxicity.
Lupp
Amelie
A
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Nonnenplan 4, 07743, Jena, Germany. amelie.lupp@mti.uni-jena.de
Glöckner
Reinhild
R
Etzrodt
Joachim
J
Müller
Dieter
D
D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006900:Hydroxylation; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis / Q000378:metabolism; D009924:Organ Culture Techniques / Q000379:methods*; D010078:Oxazines / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D019324:beta-Naphthoflavone / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D003374:Coumarins; D004791:Enzyme Inhibitors; D010078:Oxazines; D011285:Pregnenolone Carbonitrile; C017299:7-ethoxycoumarin; D013739:Testosterone; D019324:beta-Naphthoflavone; D003907:Dexamethasone; C044943:pentoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019363:Cytochrome P-450 CYP1A1; D004121:Dimethyl Sulfoxide; D010634:Phenobarbital