Comparison of cytochrome P4502E1 (CYP2E1) activity and hepatic and lymphocyte mRNA expression in patients with chronic hepatitis C.
The induction of cytochrome P4502E1 (CYP2E1) is believed to play a role in the development of fibrosis in hepatitis C patients. However, information about CYP2E1 activity in chronic hepatitis C patients is fragmentary and the relationship between CYP2E1 activity and mRNA expression is unknown in this disease. The purpose of this study was (a) to characterise CYP2E1 activity in those patients and (b) to analyse its relationship with CYP2E1 mRNA expression in the liver and in peripheral blood lymphocytes (PBLs), previously proposed as a surrogate to assess changes in CYP2E1 activity. Fourteen chronic hepatitis C patients were submitted to a routine transcutaneous liver biopsy. CYP2E1 activity was assessed by using chlorzoxazone (CZX) pharmacokinetic parameters and hepatic and PBLs CYP2E1 mRNA expression was measured by real-time RT-PCR. The mean oral clearance of CZX (CLT: 21.5+/-10.1L/h) was within the normal range and the chlorzoxazone metabolic ratio (CMR) at t = 2 h was closely related to other CZX pharmacokinetic parameters. None of the pharmacokinetic parameters did significantly correlate with CYP2E1 mRNA, neither in the liver nor in PBLs. Furthermore, there was no significant relationship between CYP2E1 mRNA levels in paired liver and PBL samples. Our data indicate that early stages of chronic hepatitis C are not associated with CYP2E1 induction. In this disease, the determination of the CMR at t = 2 h represents a reliable index to assess CYP2E1 activity. The measurement of CYP2E1 expression, at the mRNA level, in PBLs or in liver is not useful for that purpose.
Haufroid
Vincent
V
Industrial and Environmental Toxicology Unit, Université catholique de Louvain, Clos Chapelle-aux-Champs 30/54, B-1200, St. Luc Hospital, Brussels B-1200, Belgium. haufroid@toxi.ucl.ac.be
Ligocka
Danuta
D
Wallemacq
Pierre
P
Lison
Dominique
D
Horsmans
Yves
Y
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002753:Chlorzoxazone / Q000378:metabolism / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D019698:Hepatitis C, Chronic / Q000201:enzymology*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000378:metabolism / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009125:Muscle Relaxants, Central; D012333:RNA, Messenger; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone