Jejunal crypt cell abnormalities associated with methotrexate treatment in children with acute lymphoblastic leukaemia.

Abstract

SUMMARY Jejunal mucosal crypts were examined in jejunal biopsies from eight children with acute lvmphoblastic leukaemia who had recently received methotrexate treatment. By comparison with biopsies from children under investigation for suspected malabsorption crypt mitosis was significantly reduced and showed a negative correlation with the dose of methotrexate given prior to biopsy. The three major cell types were studied under light and transmission electron microscopy. Gut endocrine cells were unaffected by therapy and immature crypt enterocytes showed only patchy degenerative abnormalities. By contrast a number of Paneth cells showed striking structural alterations with vacuolar dilatation of the cytoplasm. The extent of this correlated with the time since methotrexate treatment rather than its dose and may have been a functional response rather than of a toxic nature.

Selective sparing of goblet cells and Paneth cells in the intestine of methotrexate-treated rats

“…The use of the cytostatic drug methotrexate (MTX) in anticancer treatments may severely impair intestinal epithelial function and therefore constitutes a doselimiting factor in treatment schedules (20). Like other chemotherapeutics, it induces diarrhea and anorexia, accompanied by malabsorption, malnutrition, and dehydration.…”

Methotrexate enterotoxicity: Influence of drug dose and timing in the rat

“…(Trier, 1962;Pinkerton et al, 1982) but the cellular response to such inhibition is variable. This may range from a harmless delay in cell division to cell death and appears to depend upon both the metabolic state of the enterocyte and the stage of cell division at the time of drug exposure (Farber, 1971).…”

Effect of Oral Glutamine on Enterocyte Turnover during Methotrexate-Induced Mucositis in Rats

“…The primary toxic effects of MTX are myelosuppression and or intestinal mucositis, which occur 5–14 days after the dose. Like γ-irradiation, MTX induces gastrointestinal ulceration, diarrhea and anorexia, which is associated with malabsorption, malnutrition and dehydration [3]. As a folic acid analogue, MTX primarily inhibitsDNA synthesis by binding to the enzyme dihydrofolate reductase.…”