A preliminary evaluation of drug biotransformation in hepatocytes of genetically defined rat strains.
This study was directed to use the genetically developed isoprenaline-sensitive (S), isoprenaline-resistant (R) and spontaneous hypertensive rats (SHR) as standard diseased animal models for in vitro liver function evaluation of drug biotransformation. Hepatic hexobarbital hydroxylase and glutathione transferase (GST) were evaluated by using hexobarbital and 1-chloro-2,4-dinitrobenzene (CDNB) as substrates, at concentrations of 0.21 mmol/l and 1 mmol/l, respectively. The assay was conducted by using isolated hepatocytes in suspension and hepatocytes in a bioreactor configuration. The data demonstrate that there are certain cellular pharmacokinetic differences in hexobarbital hydroxylase and GST activities in hepatocytes obtained from Wistar, SHR, R and S strains which can be better demonstrated, when using the model of perfused and immobilized hepatocytes.
Hynie
S
S
Institute of Pharmacology, First Medical Faculty, Charles University, Prague, Czech Republic.
Kren
V
V
Bílá
V
V
Mráz
M
M
Gaier
N
N
Kameníková
L
L
Farghali
H
H
D000818:Animals; D001709:Biotechnology / Q000379:methods; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004137:Dinitrochlorobenzene / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006591:Hexobarbital / Q000378:metabolism; D008658:Inactivation, Metabolic; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010477:Perfusion / Q000379:methods; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D017208:Rats, Wistar
D004137:Dinitrochlorobenzene; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; C021352:hexobarbital hydroxylase; D005982:Glutathione Transferase