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Retinoid toxicity.

J A Turton, R M Hicks, J Gwynne

    Ciba Foundation Symposium
    |January 1, 1985
    PubMed
    Summary
    This summary is machine-generated.

    N-ethylretinamide (NER) reduced red blood cell counts and fibrinogen in rats. Retinoids also affected lymphoid organs and caused dose-related long-bone changes in mice and rats.

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    Area of Science:

    • Toxicology
    • Pharmacology
    • Skeletal Biology

    Background:

    • Retinoids are crucial for various physiological processes.
    • Understanding retinoid toxicity, particularly skeletal and hematological effects, is vital.
    • Investigating dose-response relationships and potential mitigation strategies is necessary.

    Purpose of the Study:

    • To assess the long-term hematological effects of N-ethylretinamide (NER) in rats.
    • To investigate dose-related impacts of retinoids on lymphoid organs and long bones in rodents.
    • To explore the efficacy of non-steroidal anti-inflammatory compounds (NSAICs) in preventing retinoid-induced skeletal alterations.

    Main Methods:

    • Hematological analysis in NER-fed rats.
    • Histopathological examination of lymphoid organs (spleen, lymph nodes) in mice and rats.

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  • Quantitative assessment of retinoid-induced long-bone changes (femoral diaphysis and medullary cavity).
  • In vivo studies evaluating the preventative effects of NSAICs against retinoid-induced skeletal changes.

    • Main Results:

    • N-ethylretinamide (NER) administration led to decreased red blood cell counts and fibrinogen levels in rats.
    • Retinoids induced dose-dependent lymphoid organ proliferation in mice and to a lesser extent in rats.
    • Significant dose-related reductions in femoral diaphysis and medullary cavity diameters were observed in both rats and mice.
    • Aspirin demonstrated a preventative effect on NER-induced rat long-bone changes, contingent on specific dosing.

    Conclusions:

    • Retinoids, including NER, exert significant hematological and skeletal effects in rodents.
    • Lymphoid organ responses and long-bone remodeling are dose-dependent.
    • NSAIDs may offer protection against retinoid-induced skeletal toxicity, but dosage is critical.
    • Retinoid-induced bone remodeling is rapid but potentially reversible, with age-dependent variations.