title: Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis.
abstract: BACKGROUND
  Patients with chemotherapy-induced gastrointestinal mucositis often suffer from weight loss. It is not well known how to enterally feed mucositis patients, potentially experiencing malabsorption. Recently, we showed in a rat model of methotrexate (MTX)-induced mucositis that intestinal absorption of glucose in trace amounts is still intact. We now determined the quantitative capacity to absorb glucose in rats with mucositis, relative to controls.
  
  
  METHODS
  We administered a physiologically relevant amount of [1-(13)C]glucose-enriched glucose (meal size) as a bolus by oral gavage (2 g/kg once) or continuously by intraduodenal infusion (±1.9 g/(kg·h) for 5 h) to rats with MTX-induced mucositis and controls. Blood [1-(13)C]glucose concentrations were determined during the experimental period. To calculate the quantitative absorptive capacity, Steele's one-compartment model, including simultaneous intravenous infusion of [6,6-(2)H(2)]glucose, was used. After the experiment, jejunal histology and plasma citrulline concentrations were assessed.
  
  
  RESULTS
  MTX-induced mucositis was confirmed by a reduction in villus length and plasma citrulline (both -57%, relative to controls, P < 0.01). When glucose was administered as a bolus, MTX-treated rats only absorbed 15% of administered glucose, compared with 85% in controls (medians, P < 0.01). Upon continuous intraduodenal glucose infusion, the median absorptive capacity for glucose in MTX-treated rats did not differ from controls (80 versus 93% of administered glucose respectively, P = 0.06). However, glucose absorption differed substantially between individual MTX-treated rats (range, 21-95%), which correlated poorly with villus length (rho = 0.54, P = 0.030) and plasma citrulline (rho = 0.56, P = 0.024).
  
  
  CONCLUSIONS
  Continuous enteral administration can almost completely overcome the reduced absorptive capacity for glucose in rats with mucositis.
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, Groningen University Institute for Drug Exploration, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Margot
authors.initials: M
authors.lastname: Fijlstra
authors.forename: Edmond H H M
authors.initials: EH
authors.lastname: Rings
authors.forename: Theo H
authors.initials: TH
authors.lastname: van Dijk
authors.forename: Torsten
authors.initials: T
authors.lastname: Plösch
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.forename: Wim J E
authors.initials: WJ
authors.lastname: Tissing
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D002956:Citrulline / Q000097:blood; D004750:Enteral Nutrition / Q000379:methods*; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D052016:Mucositis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000964:Antimetabolites, Antineoplastic; D002956:Citrulline; D005947:Glucose; D008727:Methotrexate