Precision-Cut Organ Slices as a Tool to Study Toxicity and Metabolism of Xenobiotics with Special Reference to Non-Hepatic Tissues

Authors: Kanter R.de; Monshouwer M.; Meijer D.K.F.; Groothuis G.M.M.

Source: Current Drug Metabolism, Volume 3, Number 1, February 2002 , pp. 39-59(21)

Publisher: Bentham Science Publishers

Abstract:

Metabolism of xenobiotics is often seen as an exclusive function of the liver, but some current findings support the notion that the lungs, kidneys and intestine may contribute considerably. After the establishment of the use of liver slices as a useful in vitro model to study metabolism and toxicity of xenobiotics, the same concept is currently being used for slices from lung, kidney and intestine. It is the aim of this review to discuss the use of organ slices in biotransformation research.

The basic idea behind the use of tissue slices in biomedical research is the assumption that the cells under study will function optimally in vitro if they are cultivated in an environment that is most alike to their natural in vivo embedding, which is the case in tissue slices.

Advantages in the use of organ slices are the relatively easy preparation as well as the potential standardization of both the preparation and use. Moreover, a direct interspecies comparison can be made between liver, lungs, kidneys and intestines, for example with respect to their metabolic capacity and their sensitivity for toxicants. Of major importance is that organ slices can be made with a similar procedure from organs / tissues originating from different species, including man. This latter aspect is useful in drug development in general but also for a better insight in the metabolic fate of compounds in man. Importantly the use of slices may largely contribute to a reduction in the use of experimental animals.

Keywords: Xenobiotics; CYP3A4; MDR1 P-glycoprotein (P-gp); Dynamic Organ Culture (DOC)

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389200023338071

Publication date: 2002-02-01

• Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
  
  In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

• In this: publication
• By this: publisher
• In this Subject: Anatomy & Physiology ,  Pharmacology
• By this author: Kanter R.de ;  Monshouwer M. ;  Meijer D.K.F. ;  Groothuis G.M.M.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers