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Effect of topical application of clotrimazole to rats on epidermal and hepatic monooxygenase activities and cytochrome P-450

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Summary

Clotrimazole, an N-substituted imidazole, is a widely used topical agent for the treatment of superficial fungal infections. In this study, the effect of application of clotrimazole to the skin of neonatal rats on the induction response of the cytochrome P-450-dependent monooxygenase system in epidermis and liver has been examined. A single topical application of clotrimazole (10 mg/100 g) to rats resulted in a 53% increase in hepatic cytochrome P-450 content. Clotrimazole treatment also resulted in significant induction of epidermal 7-ethoxycoumarin-O-deethylase activity. Hepatic p-nitrophenol hydroxylase, an enzyme, catalyzed principally by the ethanol inducible cytochrome P-450 isozyme, was also significantly induced (58%) by topically applied clotrimazole. This enzyme activity was undetectable in epidermal microsomes. Further characterization of the cytochrome P-450 isozymes induced in liver by clotrimazole treatment was based on monoclonal antibodies (MAbs) raised against purified rat liver cytochrome P-450 isozymes induced by phenobarbital (MAb 2-66-3) and ethanol (MAb 1-98-1). Hepatic microsomes prepared from clotrimazole-treated rats showed significant immunoreactivity on Western blot with both the MAbs whereas no reactivity occurred in epidermal microsomes. Our data indicate that topical application of clotrimazole to rats results in the induction of selected cytochrome P-450 isozyme(s) in liver and epidermis which may have implications for the therapeutic use of this compound.

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Authors and Affiliations

  1. Department of Dermatology, University of Cologne, Cologne, FRG

    H. F. Merk

  2. Department of Dermatology, University Hospitals of Cleveland, Cleveland, Ohio, USA

    W. A. Khan, C. Kuhn, D. R. Bickers & H. Mukhtar

  3. Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA

    W. A. Khan, C. Kuhn, D. R. Bickers & H. Mukhtar

  4. Department of Dermatology, Veterans Administration Medical Center, Cleveland, Ohio, USA

    W. A. Khan, C. Kuhn, D. R. Bickers & H. Mukhtar

Authors
  1. H. F. Merk
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  2. W. A. Khan
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  3. C. Kuhn
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  4. D. R. Bickers
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  5. H. Mukhtar
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Additional information

This study was supported in part by USPHS Grant ES-1900 and by research funds from the Veterans Administration

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Merk, H.F., Khan, W.A., Kuhn, C. et al. Effect of topical application of clotrimazole to rats on epidermal and hepatic monooxygenase activities and cytochrome P-450. Arch Dermatol Res 281, 198–202 (1989). https://doi.org/10.1007/BF00456393

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  • DOI: https://doi.org/10.1007/BF00456393

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