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 metabo lism and toxicity in target tissues (e.g. brain). Morphological and bi ochemical changes have been reported in the respiratory tract of labor atory animals exposed to styrene either by inhalation or i.p. injectio n. The aim of the present study was, therefore, to investigate the inf luence of subchronic ethanol administration (5% in a Lieber-DeCarli li quid diet) on the morphological alterations of the respiratory tract i nduced 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 live r tissues as well as in erythrocytes and whole blood were studied as i ndicators of overall GSH status, and urinary levels of the styrene met abolites-mandelic acid and phenylglyoxylic acid-were also measured as indicators of styrene-absorbed dose. Rats exposed to 300 ppm styrene p resented morphological alterations throughout the respiratory tract. E lectron microscopy analysis showed diffuse cell damage involving the t racheal, bronchiolar and alveolar epithelium. These abnormalities were accompanied by 40% depletion of GSH in the lung tissue and also 35% d epletion in hepatic GSH in the absence of alteration of the GSH conten t in blood. Styrene metabolism was apparently induced by subchronic et hanol treatment, as indicated by an increased excretion of urinary man delic (+ 140%, P < 0.05) and phenylglyoxylic (+50%) acids. However, re peated ethanol administration did not exacerbate the lung GSH depletio n nor the damaging effect to the respiratory tract induced by the 2-we ek exposure to styrene alone. The lack of effects of ethanol on styren e pulmonary toxicity after combined exposure may be due to the differe nt tissue distribution of the cytochrome P-450 isoforms involved in th e styrene biotransformation to styrene-7,8-oxide, and their different induction by ethanol, (C) 1998 John Wiley & Sons, Ltd.