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Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
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Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures

Published on: March 28, 2017

Xenobiotics, drug metabolism, and liver injury

J L Farber

    Monographs in Pathology
    |January 1, 1987
    PubMed

    Insights

    The covalent binding hypothesis for drug-induced liver injury is challenged by new evidence. Emerging research suggests variations in mixed function oxidation cycles, not just binding, cause liver cell death from toxins like acetaminophen.

    Area of Science:

    • Biochemical Pathology
    • Toxicology
    • Hepatotoxicity

    Background:

    • The covalent binding hypothesis has long explained xenobiotic-induced liver injury.
    • This hypothesis links reactive metabolites binding to macromolecules with liver cell death.
    • Evidence is largely circumstantial, based on correlations between binding extent and necrosis severity.

    Purpose of the Study:

    • To review alternative mechanisms of xenobiotic-induced liver injury.
    • To explore emerging schemes emphasizing variations in mixed function oxidation.
    • To discuss biochemical lesions caused by specific hepatotoxins.

    Main Methods:

    • Review of recent studies on haloalkanes, aryl halides, and redox-cycling compounds.
    • Analysis of variations in the mixed function oxidation cycle.
    • Examination of three classic hepatotoxins: carbon tetrachloride, acetaminophen, and bromobenzene.

    Main Results:

    • Recent studies suggest alternative mechanisms beyond covalent binding for hepatotoxicity.
    • Variations in the mixed function oxidation cycle, influenced by hepatotoxin properties, are implicated.
    • Specific biochemical lesions associated with carbon tetrachloride, acetaminophen, and bromobenzene toxicity were discussed.

    Conclusions:

    • The role of covalent binding in xenobiotic hepatotoxicity requires re-evaluation.
    • Variations in mixed function oxidation represent a key mechanism in liver cell injury.
    • Understanding these variations is crucial for elucidating the precise mechanisms of hepatotoxin-induced damage.

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