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) contentsand activities were tested in liver, kidney and lung from Wistarrats after the following treatments (1) oral administrationof a 10% ethanol solution 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 activitywas measured using chlorzoxazone as substrate and CYP2E1 contentwas measured using Western blot analysis. In addition, the cellulardistribution of CYP2E1 was studied in liver, lung and kidneyby immunohistochemistry. Basal liver CYP2E1 was 10–20times lower in lung and kidney than in liver. Inhalation wasclearly the most efficient way of inducing CYP2E1, probablydue to the continuous and high alcohol exposure. Among the organstested, lung appeared to be the tissue least sensitive to inductioneven after ethanol inhalation, suggesting the absence of localinduction. After ethanol intoxication, immunostaining was increasedin the centrilobular region of the liver, in the alveolar cellsof the lung and in the proximal convoluted tube of the kidney.The CYP2E1 activities decreased to control values in the threetissues tested, within 24 h after cessation of intoxication.