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Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis

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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 [1-13C]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 [1-13C]glucose concentrations were determined during the experimental period. To calculate the quantitative absorptive capacity, Steele’s one-compartment model, including simultaneous intravenous infusion of [6,6-2H2]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).

Conclusion

Continuous enteral administration can almost completely overcome the reduced absorptive capacity for glucose in rats with mucositis.

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Acknowledgments

The authors wish to thank Rick Havinga, Juul Baller, Theo Boer, Angelika Jurdzinski, and Pieter Klok for the excellent technical assistance in our studies.

Grants

This study was financially supported by an unrestricted research grant from Fonds NutsOhra.

Conflict of interest

We have nothing to declare. All authors have full control of all primary data and agree to allow the journal to review the data if requested.

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Authors and Affiliations

  1. Department of Pediatric Gastroenterology and Hepatology, Beatrix Children’s Hospital, Groningen University Institute for Drug Exploration (GUIDE), Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, HPC CA70, P.O. Box 30.001, 9700 RB, Groningen, the Netherlands

    Margot Fijlstra, Edmond H. H. M. Rings, Theo H. van Dijk, Torsten Plösch & Henkjan J. Verkade

  2. Department of Pediatric Oncology, Beatrix Children’s Hospital, Groningen University Institute for Drug Exploration (GUIDE), Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, HPC CA21, P.O. Box 30.001, 9700 RB, Groningen, the Netherlands

    Margot Fijlstra & Wim J. E. Tissing

Authors
  1. Margot Fijlstra
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  2. Edmond H. H. M. Rings
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  3. Theo H. van Dijk
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  5. Henkjan J. Verkade
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  6. Wim J. E. Tissing
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Corresponding author

Correspondence to Wim J. E. Tissing.

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Relevance of our manuscript to inform research, policies, and/or programs

In our manuscript, we show that continuous enteral administration can almost completely overcome the reduced absorptive capacity for glucose in rats with chemotherapy-induced gastrointestinal mucositis. Glucose might therefore be an appropriate source of dietary energy for a substantial portion of patients with mucositis, when enterally administered continuously. Our work is relevant for everybody who is involved in the feeding strategy of patients with mucositis (doctors, dieticians, caretakers, food industries, etc.).

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Fijlstra, M., Rings, E.H.H.M., van Dijk, T.H. et al. Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis. Support Care Cancer 21, 863–871 (2013). https://doi.org/10.1007/s00520-012-1597-2

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