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.
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.
Unité de Pharmacocinétique, Métabolisme, Nutrition, et Toxicologie (PMNT), Département des Sciences Pharmaceutiques, Université Catholique de Louvain, 73 Avenue Mounier, 1200 Bruxelles, Belgium.
Valérie
V
Wauthier
Roger K
RK
Verbeeck
Pedro
P
Buc Calderon
D000082:Acetaminophen / Q000378:metabolism / Q000633:toxicity*; D000375:Aging / Q000502:physiology*; D018712:Analgesics, Non-Narcotic / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D051544:Cytochrome P-450 CYP3A; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D008867:Microtomy; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating