title: Reduced absorption of long-chain fatty acids during methotrexate-induced gastrointestinal mucositis in the rat.
abstract: OBJECTIVE
  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-(13)C]palmitic acid) and unsaturated ([U-(13)C]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-(13)C]palmitic- and [U-(13)C]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-(13)C]palmitic acid appearance was higher than [U-(13)C]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.
authors.affiliation: Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, Groningen University Institute for Drug Exploration (GUIDE), University of Groningen, University Medical Center Groningen, HPC CA70, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. m.fijlstra@med.umcg.nl
authors.forename: Margot
authors.initials: M
authors.lastname: Fijlstra
authors.forename: Wim J E
authors.initials: WJ
authors.lastname: Tissing
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.forename: Edmond H H M
authors.initials: EH
authors.lastname: Rings
mesh_terms: D000042:Absorption; D000818:Animals; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D019787:Linoleic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D052016:Mucositis / Q000139:chemically induced / Q000473:pathology*; D019308:Palmitic Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019308:Palmitic Acid; D019787:Linoleic Acid; D008727:Methotrexate