Dynamics of cytochrome P4502E1 activity in man: induction by ethanol and disappearance during withdrawal phase.
OBJECTIVE
Chronic ethanol consumption results in the induction of hepatic cytochrome P4502E1 (CYP2E1) in man, which is believed to play an important role in the pathogenesis of alcoholic liver disease. However, the amount and duration of alcohol intake associated with CYP2E1 induction is not known but limited information is available on the disappearance of CYP2E1 following alcohol withdrawal.


METHODS
To study these questions, five healthy male volunteers received ethanol daily (40 g/day) over 4 weeks. CYP2E1 induction was monitored by using the chlorzoxazone test before and every week following the start of alcohol ingestion. In addition, CYP2E1 was also determined in five alcoholics 1, 3, 8 and 15 days following ethanol withdrawal and in five patients with non-alcoholic liver disease.


RESULTS
A significant CYP2E1 induction occurred 1 week following the ingestion of 40 g ethanol per day and increased further after 4 weeks. The disappearance of CYP2E1 was found to be significant 3 days following ethanol withdrawal and further decreased up to day 8. Thereafter, no significant change occurred and CYP2E1 activities were comparable with those in patients with non-alcoholic liver disease.


CONCLUSIONS
These data show a significant and quick induction of CYP2E1 activity, already at moderate alcohol consumption, which may be of importance in the pathogenesis of alcoholic liver disease, of ethanol, drug and vitamin A interactions and in alcohol associated carcinogenesis.
Oneta
Carl M
CM
Division of Gastroenterology, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) et Policlinique Médicale Universitaire (PMU), Lausanne, Switzerland.
Lieber
Charles S
CS
Li
JunJie
J
Rüttimann
Sigmund
S
Schmid
Beat
B
Lattmann
Jürg
J
Rosman
Alan S
AS
Seitz
Helmut K
HK
D000428:Alcohol Drinking / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism; D002273:Carcinogens; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000493:pharmacokinetics*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D013375:Substance Withdrawal Syndrome
D002273:Carcinogens; D002492:Central Nervous System Depressants; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1