Reduced absorption of long-chain fatty acids during methotrexate-induced gastrointestinal mucositis in the rat

Margot Fijlstra, Wim J.E. Tissing, Frans Stellaard, Henkjan J. Verkade, Edmond H.H.M. Rings

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Background & aims: Patients with chemotherapy-induced gastrointestinal mucositis suffer from weight loss and possibly malabsorption. Since long-chain fatty acids serve important functions in the body, we aimed to determine the intestinal capacity of fat absorption in rats with and without methotrexate-induced mucositis. Methods: Four days after intravenous injection with methotrexate (60 mg/kg) or saline, rats received saturated ([U-13C]palmitic acid) and unsaturated ([U-13C]linoleic acid) fatty acids dissolved in oil, either as a single bolus by oral gavage or by continuous intraduodenal infusion. We determined plasma and liver label concentrations at specific time points. Results: We confirmed methotrexate-induced mucositis by villus atrophy using microscopy. Methotrexate treatment severely reduced the appearance of [U-13C]palmitic- and [U-13C]linoleic acid in plasma and liver, compared to controls, either when administered as a bolus or continuously (all at least -63%, P < 0.05). Liver [U-13C]palmitic acid appearance was higher than [U-13C]linoleic acid appearance, either when administered as a bolus (2.8-fold, P < 0.01) or continuously (5.7-fold, P < 0.01). Conclusions: The intestinal capacity to absorb long-chain fatty acids is severely reduced in rats with methotrexate-induced mucositis. Continuous administration does not overcome this impairment. The liver takes up and/or retains mainly saturated fatty acids during mucositis.

Original languageEnglish
Pages (from-to)452-459
Number of pages8
JournalClinical Nutrition
Issue number3
Publication statusPublished - Jun 2013
Externally publishedYes


  • Chemotherapy
  • Citrulline
  • Gastrointestinal mucositis
  • Liver fatty acid appearance
  • Long-chain fatty acids
  • Nutrient absorption


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