title: Pneumotoxicity and hepatotoxicity of styrene and styrene oxide.
abstract: The purpose of this study was to investigate the toxicity of styrene and styrene oxide in the lung in comparison to the toxicity in the liver. Pneumotoxicity caused by styrene or styrene oxide was measured by elevations in the release of gamma-glutamyltranspeptidase (GGT) and lactate dehydrogenase (LDH) into bronchoalveolar lavage fluid (BALF), while hepatotoxicity was measured by increases in serum sorbitol dehydrogenase (SDH) in non-Swiss Albino (Hsd:NSA) mice. Intraperitoneal administration of styrene at doses of 500-1000 mg/kg caused consistent dose-dependent increases in both sets of biomarkers with the hepatic effect appearing earlier than the pulmonary effect. Pyridine, phenobarbital, and beta-naphthoflavone, inducers of CYP2E1, CYP2B, and CYP1A, respectively, increased the toxicity of styrene. Pyridine and phenobarbital treatments increased mortality due to styrene. Styrene oxide exists in two enantiomeric forms: (R)- and (S)-styrene oxide, and the differential toxicities of the two enantiomers and racemic styrene oxide were compared. In all studies, (R)-styrene oxide caused greater toxicity than the (S) enantiomer, especially in the liver. Trichloropropene oxide, an epoxide hydrolase inhibitor, was used to inhibit styrene oxide detoxification and increased its hepatotoxicity, while buthionine sulfoxamine, a glutathione depletor, did not. These results demonstrated the greater role of epoxide hydrolase in styrene oxide detoxification.
authors.affiliation: Department of Pharmacology and Toxicology, Purdue University, West Lafayette, Indiana 47907-1334, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Gadberry
authors.forename: D B
authors.initials: DB
authors.lastname: DeNicola
authors.forename: G P
authors.initials: GP
authors.lastname: Carlson
mesh_terms: D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019328:Buthionine Sulfoximine; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020058:Styrene; D013343:Styrenes / Q000008:administration & dosage / Q000633:toxicity*; D014239:Trichloroepoxypropane / Q000494:pharmacology; D019324:beta-Naphthoflavone; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D001571:Benzoflavones; D002273:Carcinogens; D004852:Epoxy Compounds; D011725:Pyridines; D013343:Styrenes; D008717:Methionine Sulfoximine; D014239:Trichloroepoxypropane; D020058:Styrene; D019328:Buthionine Sulfoximine; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; C013690:styrene oxide; D007064:L-Iditol 2-Dehydrogenase; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; C023666:pyridine; D010634:Phenobarbital