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Heavy metals and enzyme induction.

T Stoytchev, M Kadiiska

    Acta Physiologica Et Pharmacologica Bulgarica
    |January 1, 1983
    PubMed
    Summary
    This summary is machine-generated.

    Heavy metal salts impact drug metabolism enzymes in rats. Some metals, at subtoxic doses, induce enzymes, while toxic doses inhibit drug metabolism, affecting drug interactions.

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    Area of Science:

    • Toxicology
    • Biochemistry
    • Pharmacology

    Background:

    • Heavy metals are environmental contaminants with known toxic effects.
    • Drug metabolism enzymes, like cytochrome P450, are crucial for xenobiotic detoxification.
    • Phenobarbital and methylcholanthrene are known inducers of drug metabolism enzymes.

    Purpose of the Study:

    • To investigate the effects of various heavy metal salts on the enzyme-inducing actions of phenobarbital and methylcholanthrene.
    • To determine if subtoxic doses of heavy metal salts exhibit enzyme-inducing properties.
    • To assess the impact of heavy metals on hexobarbital sleeping time, ethylmorphine-N-demethylase activity, and cytochrome P-450 content.

    Main Methods:

    • Experiments were conducted on male albino rats.

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  • Single toxic doses of heavy metal salts were administered.
  • Subtoxic doses of specific heavy metal salts were administered daily for 30 days.
  • Enzyme-inducing actions were assessed by measuring ethylmorphine-N-demethylase and aniline hydroxylase activities.
  • Hexobarbital sleeping time, liver microsomal cytochrome P-450 content were also measured.

    • Main Results:

    • Single toxic doses of most heavy metal salts (Cu, Co, Cd, Pb, Ni, Zn, Hg) inhibited methylcholanthrene-induced aniline hydroxylase activity more than phenobarbital-induced ethylmorphine-N-demethylase activity.
    • Subtoxic daily oral doses of Co, Cd, Zn, and Ni salts shortened hexobarbital sleeping time and increased ethylmorphine-N-demethylase activity and cytochrome P-450 content.
    • Cu, Bi, Sn, and Pb did not induce enzymes; As and Hg showed inconsistent effects.

    Conclusions:

    • Heavy metal salts exhibit differential effects on drug metabolism enzyme induction.
    • Subtoxic oral exposure to certain heavy metals (Co, Cd, Zn, Ni) can induce drug metabolism enzymes in rats.
    • Toxic doses of heavy metals can inhibit phenobarbital and methylcholanthrene-induced enzyme activity, suggesting potential for drug interactions.