PMID- 15465655 OWN - NLM STAT- MEDLINE DCOM- 20050225 LR - 20131121 IS - 0887-2333 (Print) IS - 0887-2333 (Linking) VI - 18 IP - 6 DP - 2004 Dec TI - 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. PG - 879-85 AB - 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. FAU - Wauthier, Valerie AU - Wauthier V AD - Unite de Pharmacocinetique, Metabolisme, Nutrition, et Toxicologie (PMNT), Departement des Sciences Pharmaceutiques, Universite Catholique de Louvain, 73 Avenue Mounier, 1200 Bruxelles, Belgium. FAU - Verbeeck, Roger K AU - Verbeeck RK FAU - Buc Calderon, Pedro AU - Buc Calderon P LA - eng PT - Journal Article PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Analgesics, Non-Narcotic) RN - 362O9ITL9D (Acetaminophen) RN - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases) RN - EC 1.14.14.1 (Cytochrome P-450 CYP3A) RN - EC 1.5.- (Oxidoreductases, N-Demethylating) SB - IM MH - Acetaminophen/metabolism/*toxicity MH - Aging/*physiology MH - Analgesics, Non-Narcotic/metabolism/*toxicity MH - Animals MH - Aryl Hydrocarbon Hydroxylases/*biosynthesis MH - Cytochrome P-450 CYP3A MH - Enzyme Induction MH - Liver/drug effects/*enzymology/growth & development MH - Microtomy MH - Oxidoreductases, N-Demethylating/*biosynthesis MH - Rats MH - Rats, Wistar EDAT- 2004/10/07 09:00 MHDA- 2005/02/26 09:00 CRDT- 2004/10/07 09:00 PHST- 2003/12/22 00:00 [received] PHST- 2004/04/28 00:00 [accepted] PHST- 2004/10/07 09:00 [pubmed] PHST- 2005/02/26 09:00 [medline] PHST- 2004/10/07 09:00 [entrez] AID - S0887233304000918 [pii] AID - 10.1016/j.tiv.2004.04.013 [doi] PST - ppublish SO - Toxicol In Vitro. 2004 Dec;18(6):879-85. doi: 10.1016/j.tiv.2004.04.013.