CYTOCHROME P4502E1 INDUCIBILITY AND HYDROXYETHYL RADICAL FORMATION AMONG ALCOHOLICS

Background/Aims: Animal studies have shown that the induction of cytoc hrome P4502E1 (CYP2E1) modulates oxidative damage induced by ethanol, Since CYP2E1 activity varies substantially in humans, we have investig ated whether differences in CYP2E1 activity might influence the format ion of hydroxyethyl free radicals and the stimulation of lipid peroxid ation among alcohol abusers. Methods: Chlorzoxazone oxidation, an inde x of CYP2E1 activity, and the levels of antibodies reacting with hydro xyethyl radical and malonyldialdehyde protein adducts were investigate d in 51 alcoholic patients. Results: We observed that in 40 out of 51 (78%) alcoholics, chlorzoxazone oxidation was increased over the contr ol levels, consistently with CYP2E1 induction by ethanol, However, in the remaining 22% of the patients, in spite of a similar alcohol intak e, chlorzoxazone oxidation was within the control range, indicating a lack of CYP2E1 inducibility. IgG reacting with hydroxyethyl free radic al-protein adducts were absent in subjects without CYP2E1 induction, w hile they were significantly increased in alcoholics with induced CYP2 E1 activity, IgG against malonyldialdehyde protein-adducts were increa sed in all patients, irrespective of CYP2E1 inducibility, Moreover, ch lorzoxazone oxidation was significantly lower in alcoholics without cl inical and biochemical signs of liver disease as compared to patients with alcoholic liver disease. Conclusions: These results indicate that CYP2E1 activity greatly influences the formation of hydroxyethyl radi cals in humans, and suggest a possible role of CYP2E1 in the developme nt of alcoholic liver disease.