Evaluation of cultures and co-cultures of hepatocytes as an in vitro model for biotransformation- and toxicity studies of drugs.

Project Details

Description

The present research project is infull agreement with current basic research at the dept. of Toxicology and provides further investigation of the model "co-cultures of hepatocytes with epithelial cells" as an alternative for in vivo toxicity and biotransformation studies of drugs. The project links up with previous projects supported by the Belgian National Science Foundation (NFWO) and the Research Council (OZR) of the VUB as well as with two new projects of the dept. of Toxicology funded by the EEC (DG XI). The project entails : - Investigation of the phase I biotransformation-enzyme flavine containing mono-oxygenase. There has been some in vivo research on this key biotransformation system yet in vitro research is still lacking. The different iso-enzymes are responsible for the oxygenation of N-, S-, Se- and P- containing drugs. Investigations will be conducted on three levels, viz. that of the enzymes, the proteins, and of mRNA - A second part will consist of the study of the glutathione dependent detoxification system in cultures and co-cultures. The hypothesis is that oxidative stress -which is presumably higher in cultures than in co-cultures - is at the basis of the dedifferentiation in biotransformation systems - which, again, has been observed to a greater extentin cultures than in co-cultures. This hypothesis will be investigated by examining the connection between peroxidation, malondialdehyde production, glutathione concentration, glutathione reductase, and glutathione peroxidase activity in various culture conditions.
Acronym1933321130
StatusFinished
Effective start/end date1/01/9330/09/97

Keywords

  • toxicology
  • biomedische technologie
  • farmacologie
  • farmaceutischeproducten

Flemish discipline codes

  • Basic sciences
  • Pharmaceutical sciences