1: Toxicol In Vitro. 2004 Dec;18(6):879-85. 

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.

Wauthier V, Verbeeck RK, Buc Calderon P.

Unite de Pharmacocinetique, Metabolisme, Nutrition, et Toxicologie (PMNT),
Departement des Sciences Pharmaceutiques, Universite Catholique de Louvain, 73
Avenue Mounier, 1200 Bruxelles, Belgium.

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.

PMID: 15465655 [PubMed - in process]