Liver slices in dynamic organ culture. I. An alternative in vitro technique for the study of rat hepatic drug metabolism

Xenobiotica. 1991 Mar;21(3):331-9. doi: 10.3109/00498259109039473.

Abstract

1. Precision-cut liver slices in dynamic organ culture, a novel in vitro technique, is described and applied to the study of hepatic drug metabolism in the rat. 2. These slices catalysed the oxidative O-deethylation of the substrate, 7-ethoxycoumarin, over 6 h incubation. In addition, the direct conjugation of 7-hydroxycoumarin with either sulphate or glucuronic acid was maintained over 6 h. 3. The formation of 7-hydroxycoumarin and the presence of the sulphate and glucuronide conjugates in slices exposed to 7-ethoxycoumarin demonstrated integrated phase I and phase II drug metabolizing activities in this system. 4. Minor modifications of the incubation system allowed for the metabolism of four volatile chlorinated benzenes: monochlorobenzene 1,2-, 1,3-, and 1,4-dichlorobenzenes to aqueous soluble metabolites. 5. The use of liver slices in dynamic organ culture as an alternative preparation for the study of xenobiotic metabolism is discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Buffers
  • Chlorobenzenes / metabolism
  • Coumarins / metabolism
  • Female
  • Liver / metabolism*
  • Male
  • Organ Culture Techniques
  • Pharmaceutical Preparations / metabolism*
  • Rats
  • Rats, Inbred F344
  • Umbelliferones / metabolism

Substances

  • Buffers
  • Chlorobenzenes
  • Coumarins
  • Pharmaceutical Preparations
  • Umbelliferones
  • 7-ethoxycoumarin
  • 7-hydroxycoumarin
  • 2-dichlorobenzene
  • 1,3-dichlorobenzene
  • 4-dichlorobenzene