Pulmonary toxicity of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-treated rats.
Pulmonary changes in glutathione (GSH) indicated by the concentration of non-protein sulphydryls showed a decrease of 43% in rats exposed for 5 h per day three times to 500 cm3/m3 (2100 mg/m3) styrene vapour. In these rats, only a marginal decrease was observed in the pulmonary cytochrome P450 oxidative metabolism. Following a single 24-h inhalation exposure to 500 cm3/m3 styrene, the decreases in GSH were 66% in lung but only 16% in liver. On the other hand, a multifold increase in the disposition of thioether compounds was found in urine. Pulmonary cytochrome P450-dependent metabolism was decreased, shown by low residual activities of 7-ethoxyresorufin (less than 20%), 7-ethoxycoumarin (53%) and 7-pentoxyresorufin O-dealkylases (76%). Epoxide hydrolase and GSH S-transferase enzyme activities which catalyze styrene detoxification were not decreased. Styrene exposure (24 h) of acetone-, phenobarbital- or 3-methylcholanthrene-pretreated rats resulted in pulmonary effects different from each other and from those of styrene alone. Acetone potentiated the lung effect and elevated 1.5-fold urine thioether output. Inducer pretreatment seemed to be a factor aggravating styrene toxicity; in effect this was clearest in acetone-induced rats. In general, GSH depletion accompanied by inhibition of cytochrome P450-dependent oxidative drug metabolism were the earliest biochemical lesions manifested in styrene-exposed lung.
Elovaara
E
E
Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.
Vainio
H
H
Aitio
A
A
D000096:Acetone / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008168:Lung / Q000201:enzymology; D008171:Lung Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008748:Methylcholanthrene; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D020058:Styrene; D013343:Styrenes / Q000633:toxicity*; D013440:Sulfides / Q000652:urine
D013343:Styrenes; D013440:Sulfides; D000096:Acetone; D020058:Styrene; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D005978:Glutathione; D010634:Phenobarbital