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.
Glutathione peroxidase activity and selenium and vitamin E levels were measured in the plasma and erythrocytes of 25 chronic alcoholic patients without liver cirrhosis before and after 14 days of abstinence from alcohol, and compared with the levels in 25 sex- and age-matched healthy controls. Before abstinence, all three levels were shown significantly depressed in the alcoholic patients compared with the controls, in both plasma (80, 71, and 89% of control values) and erythrocytes (68, 70, and 83% of control values). After a 14-day abstinence period with no dietary supplementation, a trend towards normalization was noted in erythrocyte (vitamin E and glutathione peroxidase 74 and 91% of control values respectively), in whole blood selenium (82%) and plasma in vitamin E (74%). However, plasma selenium and glutathione peroxidase values were lower than pre-abstinence values (76% and 86% of control values respectively). Our results point to a deficiency in the antioxidant defense system of chronic alcoholics before the occurrence of severe liver disease. This lack of protection against lipoperoxides is all the more important in circumstances like chronic alcohol consumption, in which lipid peroxidation is known to increase. However, the present study also demonstrated that during 14 days of a normal diet free of ethanol, a rapid trend occurred towards the normalization of the factors.
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