Metabolism and toxicity of the styrene metabolite 4-vinylphenol in CYP2E1 knockout mice

Vogie, K.; Mantick, N.; Carlson, G.

Journal of Toxicology and Environmental Health. Part a 67(2): 145-152

2004


ISSN/ISBN: 1528-7394
PMID: 14675903
DOI: 10.1080/15287390490264785
Accession: 012300075

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Abstract
4-vinylphenol (4-VP) is a minor metabolite of styrene and is several times more potent as a hepatotoxicant and pneumotoxicant than is either the parent compound or the major metabolite of styrene, styrene oxide. 4-VP is metabolized primarily by CYP2E1 and CYP2F2. To further elucidate the possible role of 4-VP in styrene-induced toxicity and the importance of its metabolism by CYP2E1, the metabolism of 4-VP and its hepatotoxicity and pneumotoxicity were compared in wild-type and CYP2E1 knockout mice. There were no marked differences between the wild-type and knockout mice in the rates of microsomal metabolism of 4-VP in either liver or lung. This unexpected result mimics previous findings with styrene metabolism in wild-type and knockout mice. When mice were administered 100 mg/kg 4-VP ip, the knockout mice were more susceptible to hepatotoxicity, as measured by increases in serum sorbitol dehydrogenase activity, than were the wild-type mice. There was no significant difference in the pneumotoxicity between the two strains. The data suggest that, as for styrene, additional cytochromes P-450 are involved in the metabolism of 4-VP.