Effect of subchronic ethanol ingestion on styrene-induced damage to the tracheal and pulmonary epithelium of the rat

Previous studies have indicated that ethanol may affect styrene metabolism and toxicity in target tissues (e.g. brain). Morphological and biochemical changes have been reported in the respiratory tract of laboratory animals exposed to styrene either by inhalation or i.p. injection. The aim of the present study was, therefore, to investigate the influence of subchronic ethanol administration (5% in a Lieber-DeCarli liquid diet) on the morphological alterations of the respiratory tract induced by styrene inhalation (300 ppm, 6 h day^-1, 5 days a week for 2 weeks) in rats. Levels of reduced glutathione (GSH) in lung and liver tissues as well as in erythrocytes and whole blood were studied as indicators of overall GSH status, and urinary levels of the styrene metabolites - mandelic acid and phenylglyoxylic acid - were also measured as indicators of styrene-absorbed dose. Rats exposed to 300 ppm styrene presented morphological alterations throughout the respiratory tract. Electron microscopy analysis showed diffuse cell damage involving the tracheal, bronchiolar and alveolar epithelium. These abnormalities were accompanied by 40% depletion of GSH in the lung tissue and also 35% depletion in hepatic GSH in the absence of alteration of the GSH content in blood. Styrene metabolism was apparently induced by subchronic ethanol treatment, as indicated by an increased excretion of urinary mandelic (+140%, P <0.05) and phenylglyoxylic (+50%) acids. However, repeated ethanol administration did not exacerbate the lung GSH depletion nor the damaging effect to the respiratory tract induced by the 2-week exposure to styrene alone. The lack of effects of ethanol on styrene pulmonary toxicity after combined exposure may be due to the different tissue distribution of the cytochrome P-450 isoforms involved in the styrene biotransformation to styrene-7,8-oxide, and their different induction by ethanol.