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Intestinal lesions induced experimentally by methotrexate.

A Baskerville, D Batter-Hatton

    British Journal of Experimental Pathology
    |December 1, 1977
    PubMed
    Summary

    Methotrexate chemotherapy causes significant damage to the small intestine in mice, including mitotic inhibition and villous atrophy. However, intestinal mucosa rapidly recovers after methotrexate withdrawal.

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    Area of Science:

    • Gastroenterology
    • Pharmacology
    • Toxicology

    Background:

    • Methotrexate is a chemotherapy agent used to treat various cancers and autoimmune diseases.
    • Its mechanism involves inhibiting dihydrofolate reductase, crucial for cell replication.
    • Gastrointestinal toxicity is a known side effect of methotrexate therapy.

    Purpose of the Study:

    • To investigate the effects of intermittent methotrexate administration on the intestinal mucosa in a mouse model.
    • To characterize the temporal changes and severity of methotrexate-induced gastrointestinal damage.
    • To assess the reversibility of these changes upon drug withdrawal.

    Main Methods:

    • Mice received up to 9 doses of methotrexate intermittently over a 3-week period.
    • Histopathological examination of the duodenum, jejunum, ileum, caecum, and colon was performed.
    • Observations included mitotic activity, epithelial morphology, and presence of ulceration or hemorrhage.

    Main Results:

    • Early administration of methotrexate led to mitotic inhibition in the small intestine.
    • Subsequent doses caused crypt epithelial megalocytosis, abnormal mitoses, and villous degeneration, resulting in atrophy.
    • Severe damage, including focal ulceration and hemorrhage, was observed in some mice.
    • Colonic changes were milder and appeared later.
    • Rapid mucosal recovery was noted within 1 week after methotrexate withdrawal.

    Conclusions:

    • Intermittent methotrexate causes dose-dependent and progressive damage to the mouse small intestine.
    • The observed gastrointestinal changes are largely reversible upon cessation of methotrexate treatment.
    • These findings highlight the importance of monitoring and managing methotrexate-induced gastrointestinal toxicity.

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