Potential application of immobilized and perfused hepatocytes in environmental toxicology studies.
Conventional cellular models have contributed significantly to the understanding of many aspects of cell physiology and molecular biology. In these models cells are metabolically less active, due to the inefficient oxygenation and waste product buildup. Therefore perfusion methods for the cells are expected to improve cell activities. Cells have to be fixed in or on an appropriate inert carrier or support, which enables cellular perfusion, maintains integrated cellular functions and makes a bioreactor. Since isolated hepatocytes are extensively used in biomedical studies including those dealing with environmental pollutants or toxins and in xenobiotic biotransformation investigations, an efficient hepatocyte perfusion model has to be available for researchers. This research article is focusing on the value of hepatocyte immobilization as a laboratory bioreactor model and is shedding light on its potentiality in research related to public health. We demonstrate the application of this cellular model as a means to study representative phase I and phase II biotransformation reactions using hexobarbital hydroxylation and 7-ethoxycoumarin deethylation and 4-chloro 2-dinitrobenzene glutathione. Both phase I and phase II drug biotransformation in hepatocytes was demonstrated in this study non-destructively to the cells and in an efficient way. In spite of the aforementioned advantages, immobilized hepatocytes yet have relatively limited applications compared to conventional hepatocyte cellular systems. Reasons for this discrepancy are discussed. This cellular system may become popular due to the better performance of immobilized hepatocytes as compared to conventional hepatocyte culture and due to economic and ethical reasons. Naturally its applicability will cover several biomedical areas including basic research in environmental toxicology and other public health issues.
Farghali
H
H
Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Lincová
D
D
Kmonícková
E
E
Bencko
V
V
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics / Q000493:pharmacokinetics / Q000633:toxicity*
D004785:Environmental Pollutants; D015262:Xenobiotics