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Hepatic cytochrome P450 2E1 activity in nonalcoholic fatty liver disease.
- Source :
-
Journal of the Medical Association of Thailand = Chotmaihet thangphaet [J Med Assoc Thai] 2008 May; Vol. 91 (5), pp. 733-8. - Publication Year :
- 2008
-
Abstract
- 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.<br />Objective: The aim of the present study was to examine hepatic CYP2E1 activity in patients with NAFLD.<br />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.<br />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 microg/ml, respectively, p = 0.10).<br />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.
- Subjects :
- Adult
Case-Control Studies
Chlorzoxazone analogs & derivatives
Chlorzoxazone blood
Chlorzoxazone pharmacokinetics
Chlorzoxazone therapeutic use
Chromatography, High Pressure Liquid
Cytochrome P-450 CYP2E1 analysis
Female
Humans
Lipid Peroxidation
Male
Muscle Relaxants, Central blood
Muscle Relaxants, Central pharmacokinetics
Muscle Relaxants, Central therapeutic use
Oxidative Stress
Pilot Projects
Cytochrome P-450 CYP2E1 metabolism
Fatty Liver enzymology
Liver enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0125-2208
- Volume :
- 91
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of the Medical Association of Thailand = Chotmaihet thangphaet
- Publication Type :
- Academic Journal
- Accession number :
- 18672640