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The use of precision-cut liver slices from male Wistar rats as a tool to study age related changes in CYP3A induction and in formation of paracetamol conjugates.
- Source :
-
Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2004 Dec; Vol. 18 (6), pp. 879-85. - Publication Year :
- 2004
-
Abstract
- Precision-cut liver slices (PCLS) offer a lot of advantages because all heterogeneity and cell-cell interactions within the original tissue matrix are maintained. This in vitro model was used to study the effect of ageing on certain aspects of drug metabolism and liver function in young (3 months), adult (9 months) and old (24 months) Wistar male rats. Protein synthesis, an important liver function, was not modified in young, adult and old rats, suggesting that ageing does not impair liver functionality but it affects some specific targets. Among them, a decrease in total P450 in liver microsomes and the loss of CYP3A23 inducibility in PCLS were clearly observed in old rats as compared to adult rats. Finally, the amount of total paracetamol conjugates was not modified between 9 and 24 months but in old rats, sulfoconjugation of paracetamol, its major route of elimination, was decreased.
- Subjects :
- Acetaminophen metabolism
Analgesics, Non-Narcotic metabolism
Animals
Cytochrome P-450 CYP3A
Enzyme Induction
Liver drug effects
Liver growth & development
Microtomy
Rats
Rats, Wistar
Acetaminophen toxicity
Aging physiology
Analgesics, Non-Narcotic toxicity
Aryl Hydrocarbon Hydroxylases biosynthesis
Liver enzymology
Oxidoreductases, N-Demethylating biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0887-2333
- Volume :
- 18
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Toxicology in vitro : an international journal published in association with BIBRA
- Publication Type :
- Academic Journal
- Accession number :
- 15465655
- Full Text :
- https://doi.org/10.1016/j.tiv.2004.04.013