J Med Assoc Thai 2008; 91 (5):733

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Hepatic Cytochrome P450 2E1 Activity in Nonalcoholic Fatty Liver Disease
Prompila N Mail, Wittayalertpanya S , Komolmit P

Background: Nonalcoholic fatty liver disease (NAFLD) is a worldwide phenomenon spanning all the continents.
The pathogenesis of NAFLD has not been completely elucidated. One hypothesis is that hepatic cytochrome
P450 2E1 (CYP2E1) plays an important role in increasing the lipid peroxidation and oxidative stress
in NAFLD.

Objective: The aim of the present study was to examine hepatic CYP2E1 activity in patients with NAFLD.

Material and Method:
Healthy subjects were included. After an overnight fasting, the subjects were orally
administered 400 mg chlorzoxazone (CHZ) and serial blood samples were collected at 0 (predose), 0.5, 1, 1.5,
2, 2.5, 3, 3.5, 4, 5, 6 and 8 hours after dosing. For patients with NAFLD, plasma samples were collected at 0
(predose), 1.5, 2, 2.5 and 3 hours after dosing. Plasma CHZ and 6-hydroxychlorzoxazone (6-OH-CHZ) was
assayed by reversed-phase high-performance liquid chromatography (HPLC) with UV detector. Hepatic
CYP2E1 activity was calculated by using concentration ratio of 6-OH-CHZ / CHZ.

Results: High concentration levels of CHZ and 6-OH-CHZ in healthy subjects were found between 1.5 to 3
hours after the dose. At 1.5 to 3 hours, the concentration ratio of 6-OH-CHZ /CHZ of patients with NAFLD
seemed to be more than of healthy subjects. The time point which showed most different was 2.5 hours. (0.40 +
0.27 vs. 0.25 + 0.12 μg/ml, respectively, p = 0.10).

Conclusion:
Although significant difference of the concentration ratio of 6-OH-CHZ / CHZ between the two
groups was not exhibited, the data demonstrated the possibility of the increasing hepatic CYP2E1 activity in
NAFLD. The concentration ratio of 6-OH-CHZ / CHZ at the point 2.5 hours may be the best index for measuring
hepatic CYP2E1 activity in NAFLD.

Keywords:
Nonalcoholic fatty liver disease, Chlorzoxazone, CYP2E1

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