title: Decrease in cytochrome P4502E1 as assessed by the rate of chlorzoxazone hydroxylation in alcoholics during the withdrawal phase.
abstract: To evaluate cytochrome P4502E1 (CYP2E1) induction in alcoholics, the ratio of the concentrations of 6-hydroxychlorzoxazone (6-OH-CHZ) and chlorzoxazone (CHZ) was measured in blood 2 hr after CHZ ingestion using a HPLC method. This ratio was determined in controls and in alcoholic patients after 1, 2, 3, 4, 5, 8, and 21 days withdrawal. It was found to be 0.34 +/- 0.03 in 30 controls and 1.05 +/- 0.14 in 41 alcoholic patients within 2 days following ethanol withdrawal. This ratio decreased rapidly during withdrawal as attested by the short half-life of CYP2E1, which was found to be 2.5 days. Patients tested for CHZ metabolism after 8 or 21 days alcohol abstinence displayed the same ratio as controls [0.35 +/- 0.03 (n = 28) and 0.31 +/- 0.03 (n = 34), respectively]. No correlation was observed between gamma-glutamyltransferase, carbohydrate-deficient transferrin values, the amount of alcohol consumed/day, and the 6-OH-CHZ/CHZ ratio. There was no influence of smoking on the rate of CHZ hydroxylation, because smokers displayed the same ratio as nonsmokers [0.33 +/- 0.025 (n = 62) and 0.33 +/- 0.02 (n = 30), respectively]. The CHZ hydroxylation ratio seems to be a good reflection of the hepatic and extrahepatic CYP2E1 activity in humans.
authors.affiliation: Faculté de Médecine de Brest, Laboratoire de Biochimie-Nutrition, Brest, France.
authors.forename: D
authors.initials: D
authors.lastname: Lucas
authors.forename: C
authors.initials: C
authors.lastname: Ménez
authors.forename: C
authors.initials: C
authors.lastname: Girre
authors.forename: P
authors.initials: P
authors.lastname: Bodénez
authors.forename: E
authors.initials: E
authors.lastname: Hispard
authors.forename: J F
authors.initials: JF
authors.lastname: Ménez
mesh_terms: D000328:Adult; D000430:Alcohol Withdrawal Delirium / Q000201:enzymology* / Q000534:rehabilitation; D000437:Alcoholism / Q000201:enzymology* / Q000534:rehabilitation; D002753:Chlorzoxazone / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D004790:Enzyme Induction / Q000502:physiology; D006801:Humans; D006900:Hydroxylation; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000502:physiology*; D012016:Reference Values
chemical_list: C039289:6-hydroxychlorzoxazone; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D002753:Chlorzoxazone