Continuous enteral administration can enable normal amino acid absorption in rats with methotrexate-induced gastrointestinal mucositis.
It is unknown what feeding strategy to use during chemotherapy-induced gastrointestinal mucositis, which causes weight loss and possibly malabsorption. To study the absorptive capacity of amino acids during mucositis, we determined the plasma availability of enterally administered amino acids (AA), their utilization for protein synthesis, and the preferential side of the intestine for AA uptake in rats with and without methotrexate (MTX)-induced mucositis. Four days after injection with MTX (60 mg/kg) or saline (controls), rats received a primed, continuous dual-isotope infusion (intraduodenal and intravenous) of labeled L-leucine, L-lysine, L-phenylalanine, L-threonine, and L-methionine. We collected blood samples, assessed jejunal histology, and determined labeled AA incorporation in proximal and distal small intestinal mucosa, plasma albumin, liver, and thigh muscle. MTX-induced mucositis was confirmed by histology. The median systemic availability of all AA except for leucine was similar in MTX-treated rats and in controls. However, the individual availability of all AA differed substantially within the group of MTX-treated rats, ranging from severely reduced (<10% of intake) to not different from controls (>40% of intake in 5 of 9 rats). More AA originating from basolateral uptake than those originating from apical uptake were used for intestinal protein synthesis in MTX-treated rats (≥420% more, P < 0.05). We conclude that continuous enteral administration can enable normal AA absorption in rats with MTX-induced mucositis. The intestine prefers basolateral AA uptake to meet its need for AA for protein synthesis during mucositis.
Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Beatrix Children’s Hospital, Groningen University Institute for Drug Exploration (GUIDE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Margot
M
Fijlstra
Henk
H
Schierbeek
Gardi
G
Voortman
Kristien Y
KY
Dorst
Johannes B
JB
van Goudoever
Edmond H H M
EH
Rings
Wim J E
WJ
Tissing
D000042:Absorption; D000418:Albumins / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D004750:Enteral Nutrition; D005786:Gene Expression Regulation; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D052016:Mucositis / Q000139:chemically induced*; D018482:Muscle, Skeletal / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms
D000418:Albumins; D000596:Amino Acids; D019384:Nucleic Acid Synthesis Inhibitors; D008727:Methotrexate