Cytochrome P-450 2E1 activity and oxidative stress in alcoholic patients

As cytochrome P-450 2E1 (CYP2E1) induction was related to oxidativestress in experimental models, the aim of this study was toinvestigate the relationship between CYP2E1 activity and markersof oxidative stress in 40 alcoholic patients entering a rehabilitationprogramme. Plasma oxidized proteins, lipid peroxides (LPO) andantibodies against hydroxyethyl radical (HER) or malondialdehyde(MDA) adducts were assessed as markers of the production offree radicals, whereas vitamin E levels were evaluated as amarker of the antioxidant defence. CYP2E1 activity was determinedby using the 6-hydroxychlorzoxazone:chlorzoxazone blood metabolicratio, 2 h after drug intake. This ratio was increased by 4-foldin alcoholics, compared to non-alcoholic patients, and was correlatedwith daily intake of ethanol, carbohydrate-deficient transferrin,and blood alcohol level at the time of admission to hospital.Plasma levels of LPO and oxidized proteins were slightly increased(20%) in alcoholic patients when compared with the control group,whereas those of vitamin E were found to be slightly decreased(by 18%). Antibodies against HER or MDA adducts showed a verysignificant increase. However, when alcoholic patients weredivided into two groups according to low or high CYP2E1 induction,no significant difference was observed in the variation of theseparameters, except for anti-HER adducts antibodies. Therefore,our study confirms the main involvement of CYP2E1 in HER production.By contrast, CYP2E1 does not appear to be the main factor responsiblefor the oxidative stress occurring during human chronic alcoholism.Free radicals from other sources may therefore contribute significantlyto the generation of this oxidative stress.