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 activities were tested in liver, kidney and lung from Wistar rats after the following treatments (1) oral administration of 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 activity was measured using chlorzoxazone as substrate and CYP2E1 content was measured using Western blot analysis. In addition, the cellular distribution of CYP2E1 was studied in liver, lung and kidney by immunohistochemistry. Basal liver CYP2E1 was 10-20 times lower 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 the tissue least sensitive to induction even after ethanol inhalation, suggesting 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 the three tissues tested, within 24 h after cessation of intoxication.