Biomedical Engineering Reference
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1000
Negative control
Untreated
100 μ m rifampicin
800
600
400
2 dpt
3 dpt
Figure 9.2 Effect of zebrafish stage on whole zebrafish microplate CYP3A4 assay. Two and three
dpf zebrafish were treated with 100 mM rifampicin for 24 h and zebrafish CYP3A4 activity was
measured using a CYP3A4 chemiluminogenic substrate. Untreated 2 and 3dpf zebrafish served as
negative controls. Untreated zebrafish without CYP3A4 chemiluminogenic substrate were used as a
negative control for CYP3A4 assay. Data are expressed as meanSD. p < 0.001 compared with
untreated zebrafish in the same stage. RLU¼ relative luminescence units.
used as a positive control. Zebrafish treated with vehicle (0.1% DMSO) served as a
negative control.
All five human CYP3A4 inhibitors suppressed CYP3A4 functional activity in
zebrafish in a concentration-dependent manner ( p <
0.05-0.001, compared to
vehicle controls). For test concentrations ranging from 0.01 to 100
M, percent
inhibition of zebrafish CYP3A4 functional activity compared to 0.1% DMSO
control was 18-42% for disopyramide, 14-42% for erythromycin, 18-53% for
fluvoxamine, 24-69% for omeprazole, and 18-53% for cimetidine (Fig. 9.3).
m
Figure 9.3 CYP3A4 inhibition usingmicroplate-basedwhole zebrafishCYP3A4 assay. Two dpf zebrafish
were treated with CYP3A4 inhibitors for 24 h and zebrafish CYP3A4 activities were measured using a
CYP3A4 chemiluminogenic substrate. Zebrafish treated with 0.1%DMSO (vehicle) were used as a negative
control and zebrafish treated with 50
m
M dexamethasone (Dex) served as a positive control. Data are
SD. p
0.05, p
0.01, and p
expressed as mean
0.001 compared with 0.1% DMSO control.
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