The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone.
The effects of acute administration of dietary levels of ethanol and the garlic oil extract, diallyl sulphide (DAS), on cytochrome P450 2E1 (CYP2E1) activity in volunteers were studied using the selective probe substrate, chlorzoxazone (CZX). The ratio of the CZX metabolite 6- hydroxychlorzoxazone (6-OHCZX) to CZX was taken to indicate CYP2E1 activity. The mean differences between the baseline and DAS-treated (0.2 mg/kg) CYP2E1 activities were significantly different (two-tailed p value = 0.0242, n = 8). Likewise, the mean differences between the baseline and ethanol-treated (0.8 g/kg) CYP2E1 activities were also significantly different (two-tailed p value = 0.0005, n = 7). The reduction in in vivo CYP2E1 activity by DAS is consistent with reported inhibition observed in vitro. The marked reduction in CYP2E1 activity following acute ingestion of ethanol is consistent with a competitive inhibition mechanism of CZX metabolism. The inhibitory effect of DAS maybe additive with daily consumption of Allium vegetables in particular. This may explain the lower 6-OHCZX/CZX metabolic ratios measured in various European and Mexican cohorts and is consistent with the lower incidence of stomach, liver and colon cancers observed in southern Europeans.
Loizou
G D
GD
Health and Safety Laboratory, Sheffield, UK.
Cocker
J
J
D000284:Administration, Oral; D000328:Adult; D000498:Allyl Compounds / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects*; D002753:Chlorzoxazone / Q000008:administration & dosage / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000378:metabolism*; D010641:Phenotype; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D000975:Antioxidants; D002492:Central Nervous System Depressants; D009125:Muscle Relaxants, Central; D013440:Sulfides; D000431:Ethanol; C038491:allyl sulfide; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone