Hepatic Cytochrome P450 2E1 Activity in Nonalcoholic Fatty Liver Disease
Nantaporn Prompila MSc*, Supeecha Wittayalertpanya MSc*, Piyawat Komolmit MD, PhD**
Affiliation : * Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok ** Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok
Background : Nonalcoholic fatty liver disease (NAFLD) is a worldwide phenomenon spanning all the conti-
nents. The pathogenesis of NAFLD has not been completely elucidated. One hypothesis is that hepatic cyto-
chrome 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
