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Biochemical interactions and nephrotoxicity.

D M Ackerman, J B Hook

    Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology
    |June 1, 1984
    PubMed
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    Understanding xenobiotic nephrotoxicity requires considering species, strain, sex, and co-administered chemicals. These factors significantly influence drug-induced kidney damage and toxicity mechanisms.

    Area of Science:

    • Toxicology
    • Pharmacology
    • Renal Science

    Background:

    • Nephrotoxicity of xenobiotics is a critical concern in drug development.
    • Factors influencing xenobiotic nephrotoxicity are complex and multifactorial.
    • Species, strain, sex, and chemical interactions play a role in drug-induced kidney damage.

    Purpose of the Study:

    • To review the impact of various factors on xenobiotic nephrotoxicity.
    • To highlight the importance of species-specific responses to drug-induced kidney injury.
    • To explore how co-administered chemicals modulate nephrotoxic liability.

    Main Methods:

    • Literature review focusing on xenobiotic nephrotoxicity studies.
    • Analysis of species-dependent susceptibility to specific nephrotoxins (e.g., cephaloridine).

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  • Examination of sex- and strain-specific effects on chemical-induced nephrotoxicity (e.g., chloroform).

    • Main Results:

    • Cephaloridine exhibits variable nephrotoxicity across species, being highest in rabbits, lower in rats, and lowest in mice.
    • Species-specific susceptibility to cephaloridine correlates with renal cortical glutathione depletion.
    • Chloroform-induced nephrotoxicity is observed only in male mice of specific strains and is enhanced by ketones in male Sprague-Dawley rats.

    Conclusions:

    • Species, strain, sex, and co-exposure to other chemicals are critical determinants of xenobiotic nephrotoxicity.
    • Understanding these modulating factors is essential for predicting drug safety and designing less toxic compounds.
    • This knowledge aids in elucidating mechanisms of drug-induced kidney injury and improving risk assessment.