Decrease in cytochrome P4502E1 as assessed by the rate of chlorzoxazone hydroxylation in alcoholics during the withdrawal phase.
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.
Lucas
D
D
Faculté de Médecine de Brest, Laboratoire de Biochimie-Nutrition, Brest, France.
Ménez
C
C
Girre
C
C
Bodénez
P
P
Hispard
E
E
Ménez
J F
JF
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
C039289:6-hydroxychlorzoxazone; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D002753:Chlorzoxazone