S. Hynie et al., A PRELIMINARY EVALUATION OF DRUG BIOTRANSFORMATION IN HEPATOCYTES OF GENETICALLY DEFINED RAT STRAINS, Physiological Research, 43(2), 1994, pp. 131-135
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 func
tion evaluation of drug biotransformation. Hepatic hexobarbital hydrox
ylase and glutathione transferase (GST) were evaluated by using hexoba
rbital and 1-chloro-2,4-dinitrobenzene (CDNB) as substrates, at concen
trations of 0.21 mmol/l and 1 mmol/l, respectively. The assay was cond
ucted 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 strai
ns which can be better demonstrated, when using the model of perfused
and immobilized hepatocytes.