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Bioactivation and bound residues.

V Burgat-Sacaze, A Rico, P Delatour

    Food Additives and Contaminants
    |April 1, 1984
    PubMed
    Summary
    This summary is machine-generated.

    Toxic chemicals are activated into reactive metabolites that bind to cells, causing toxicity. Understanding these bioactivation pathways is crucial for assessing drug and residue safety.

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    Area of Science:

    • Toxicology
    • Biochemistry
    • Pharmacology

    Background:

    • Most toxic chemicals require bioactivation to cause harm.
    • Biotransformations generate reactive metabolites that bind to cellular components, leading to toxicity.
    • Reactive metabolites are categorized as electrophilic compounds, free radicals, or activators of oxygen species.

    Purpose of the Study:

    • To explain the bioactivation of toxic chemicals.
    • To describe the nature and toxicological significance of reactive metabolites and their adducts.
    • To assess the toxicity of parent drugs and their residues.

    Main Methods:

    • Discussion of bioactivation pathways.
    • Identification of reactive metabolite categories (electrophiles, free radicals).

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  • Examples: Acetaminophen-induced hepatic necrosis, Carbon tetrachloride-induced hepatic injury.

    • Main Results:

    • Electrophilic metabolites bind to nucleophilic cellular components (proteins, nucleic acids).
    • Free radicals bind to lipids and proteins, causing lipid peroxidation.
    • Microsomal mixed-function oxidases catalyze the formation of reactive intermediates.

    Conclusions:

    • Bioactivation is a key step in chemical toxicity.
    • Covalent adducts formed by reactive metabolites are crucial for toxicity assessment.
    • Understanding these mechanisms is essential for evaluating drug and residue safety.