Pulmonary toxicity of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-treated rats
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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 (<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-, phénobarbitalor 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.
Key wordsStyrene inhalation Phenobarbital Methylcholanthrene Acetone Microsomal drug-metabolizing enzymes Glutathione Thioethers Lung Liver Rat
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- Hietanen E, Ahotupa M, Bereziat J-C, Park SS, Gelboin HV, Bartsch H (1987) Monoclonal antibody characterization of hepatic and extrahepatic cytochrome P-450 activities in rats treated with phenobarbital or methylcholanthrene and fed various cholesterol diets. Biochem Pharmacol 36: 3973–3980CrossRefPubMedGoogle Scholar
- IARC International Agency for Research on Cancer (1987) IARC Monographs on the evaluation of the carcinogenic risks to humans. Suppl. 7, IARC, Lyon, FranceGoogle Scholar
- IPCS International Programme on Chemical Safety (1983) Styrene, Environmental Health Criteria 26. Published by World Health Organization, Geneva, pp 1–123. ISBN 92-154086-9Google Scholar
- Lubet RA, Mayer RT, Cameron JW, Nims RW, Burke MD, Wolff T, Guengerich FP (1985) Dealkylation of pentoxyresorufin: a rapid and sensitive assay for measuring induction of cytochrome(s) P-450 by phenobarbital and other xenobiotics in the rat. Arch Biochem Biophys 238: 43–48CrossRefPubMedGoogle Scholar
- Ohashi Y, Nakai Y, Harada H, Horiguchi S, Teramoto K (1982) Studies on industrial styrene poisoning: experimental studies about the damage on the mucosal membrane of respiratory tracts of rats exposed to styrene — contemporary observations of the changes in ciliary functions and fine structures. Jpn J Ind Health 24: 360–372Google Scholar
- Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 39: 2370–2378Google Scholar
- Pyykkö K, Paavilainen S, Metsä-Ketelä T, Laustiola K (1987) The increasing and decreasing effects of aromatic hydrocarbon solvents on pulmonary and hepatic cytochrome P-450 in rat. Acta Pharmacol Toxicol 60: 288–293Google Scholar
- Smith BR, Bend JR (1981) Metabolic interaction of hydrocarbons with mammalian lung. In: Hodgson E, Bend JR, Philpot RM (eds) Reviews in biochemical toxicology. Elsevier North Holland, Inc., Amsterdam, 3: 77–122Google Scholar
- Yoshihara S, Nagata K, Yoshimura H (1983) Different responsiveness of hepatic and pulmonary microsomal mixed function oxidases to phenobarbital-type and 3-methylcholanthrene-type polychlorinated biphenyls in rats. J Pharm Dyn 6: 954–962Google Scholar