CYTOCHROME-P-450 2E1 IN RAT-LIVER, KIDNEY AND LUNG MICROSOMES AFTER CHRONIC ADMINISTRATION OF ETHANOL EITHER ORALLY OR BY INHALATION

In this study, microsomal cytochrome P-450 2E1 (CYP2E1) contents and a ctivities were tested in liver, kidney and lung from Wistar rats after the following treatments (1) oral administration of a 10% ethanol sol ution for 4 weeks; (2) pair fed controls; (3) oral administration of a 5% acetone solution for 1 week; (4) inhalation of ethanol vapour for 4 weeks. CYP2E1 activity was measured using chlorzoxazone as substrate and CYP2E1 content was measured using Western blot analysis. In addit ion, the cellular distribution of CYP2E1 was studied in liver, lung an d kidney by immunohistochemistry. Basal liver CYP2E1 was 10-20 times l ower in lung and kidney than in liver. Inhalation was clearly the most efficient way of inducing CYP2E1, probably due to the continuous and high alcohol exposure. Among the organs tested, lung appeared to be th e tissue least sensitive to induction even after ethanol inhalation, s uggesting the absence of local induction. After ethanol intoxication, immunostaining was increased in the centrilobular region of the liver, in the alveolar cells of the lung and in the proximal convoluted tube of the kidney. The CYP2E1 activities decreased to control values in t he three tissues tested, within 24 h after cessation of intoxication.