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Effect of the fungicide clotrimazole on the bioconcentration of benzo[ a ]pyrene in gizzard shad ( Dorosoma cepedianum ): In vivo and in vitro inhibition of cytochrome P4501A activity
Author(s) -
Levine Steven L.,
Czosnyka Hillary,
Oris James T.
Publication year - 1997
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.5620160228
Subject(s) - dorosoma , gizzard shad , chemistry , non competitive inhibition , clotrimazole , microsome , cytochrome p450 , in vivo , biochemistry , stereochemistry , pharmacology , in vitro , metabolism , enzyme , biology , microbiology and biotechnology , antifungal , fishery , fish <actinopterygii>
Clotrimazole was found to inhibit in vivo and in vitro hepatic microsomal ethoxyresorufin O ‐deethylase (EROD) activity in gizzard shad ( Dorosoma cepedianum ). Gizzard shad pretreated with 50 mg clotrimazole/kg and then exposed for 1 or 3 d to benzo[ a ]pyrene (B a P) (0.86 μg/L) had significantly lower EROD activity compared to fish that were exposed to B a P alone. Following 1 and 3 d of B a P exposure, groups pretreated with clotrimazole had a 14‐ and 4‐fold decrease in EROD activity and had biocon‐centrated 8 and 11 times more parent B a P, respectively, compared to groups exposed to B a P alone. Addition of clotrimazole to B a P‐induced microsomes produced a type II binding spectrum and was an effective in vitro inhibitor of EROD activity. The median inhibitory concentration for EROD activity was 0.51 μM clotrimazole. Kinetic and spectral experiments suggest that the mechanism of inhibition by clotrimazole is noncompetitive. Reduction in the rate of oxidative B a P metabolism is hypothesized to result from noncompetitive inhibition of cytochrome P4501A and other P450 enzymes that metabolize B a P.