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Bleomycin inhibits hepatic mixed function oxidation.

M R Montgomery, J Furry, S Fernandez

    Research Communications in Chemical Pathology and Pharmacology
    |November 1, 1981
    PubMed
    Summary
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    Bleomycin significantly reduces liver enzyme activity, specifically ethylmorphine N-demethylase, in mice and rats after single or chronic injections. Chronic subcutaneous bleomycin decreased enzyme activity and cytochrome P450 levels in both species.

    Area of Science:

    • Pharmacology
    • Toxicology
    • Biochemistry

    Background:

    • Hepatic microsomal enzymes, particularly cytochrome P450, are crucial for drug metabolism.
    • Bleomycin is an anticancer drug with known toxicities, but its effects on drug-metabolizing enzymes are not fully elucidated.
    • Understanding bleomycin's impact on these enzymes is vital for managing potential drug interactions and toxicity.

    Purpose of the Study:

    • To investigate the effects of bleomycin on hepatic microsomal ethylmorphine N-demethylase activity.
    • To determine if bleomycin affects cytochrome P450 concentration.
    • To compare the impact of different bleomycin administration routes (subcutaneous vs. intraperitoneal) and treatment durations (single vs. chronic) on these enzymatic activities.

    Main Methods:

    • Administration of bleomycin via subcutaneous (s.c.) and intraperitoneal (i.p.) routes to athymic (nude) mice and rats.

    Related Experiment Videos

  • Assay of hepatic microsomal ethylmorphine N-demethylase activity at four days post-injection.
  • Chronic treatment protocols involving multiple bleomycin doses.
  • Measurement of cytochrome P450 concentration following chronic treatment.

    • Main Results:

    • A single bleomycin injection inhibited ethylmorphine N-demethylase activity in both species, regardless of administration route.
    • Chronic subcutaneous bleomycin treatment decreased both enzymatic activity and cytochrome P450 concentration in mice and rats.
    • Chronic intraperitoneal bleomycin administration led to decreased enzymatic activity and cytochrome P450 concentration only in rats.

    Conclusions:

    • Bleomycin exhibits inhibitory effects on hepatic drug metabolism, specifically ethylmorphine N-demethylase activity.
    • The route of administration and treatment duration influence bleomycin's impact on hepatic enzymes and cytochrome P450 levels.
    • Subcutaneous bleomycin appears to have a more consistent inhibitory effect on hepatic drug metabolism across species compared to intraperitoneal administration.