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Local effect of adenosine 5′-triphosphate on indomethacin-induced permeability changes in the human small intestine

Bours, Martijn J.a; Troost, Freddy J.c; Brummer, Robert-Jan M.b; Bast, Aaltd; Dagnelie, Pieter C.a

European Journal of Gastroenterology & Hepatology: March 2007 - Volume 19 - Issue 3 - p 245-250
doi: 10.1097/MEG.0b013e328011093c
Original Articles - Small Intestine, Coeliac Disease

Background Nonsteroidal anti-inflammatory drug (NSAID) use is associated with an elevated risk of gastrointestinal damage. As adenosine 5′-triphosphate (ATP) may play a protective role in the small intestine, our objective was to determine the local effect of ATP on small intestinal permeability changes induced by short-term challenge of the NSAID indomethacin in healthy humans.

Methods Mucosal permeability of the small intestine was assessed by the lactulose/rhamnose permeability test, that is, ingestion of a test drink containing 5 g lactulose and 0.5 g L-rhamnose followed by total urine collection for 5 h. Urinary excretion of lactulose and L-rhamnose was determined by fluorescent detection high-pressure liquid chromatography (HPLC). Basal small intestinal permeability was assessed as a control condition. As a model of increased small intestinal permeability, two doses of indomethacin were ingested before ingestion of the test drink (75 mg and 50 mg at 10 h and 1 h before the test drink, respectively). Concomitantly with indomethacin ingestion, placebo or 30 mg/kg ATP was administered through a naso-intestinal tube.

Results Median urinary lactulose/rhamnose ratio (g/g) in the control condition was 0.023 (interquartile range: 0.013–0.041). Compared with the control condition, urinary lactulose/rhamnose ratio after ingestion of indomethacin and administration of placebo was significantly increased [0.042 (0.028–0.076); P<0.01]. In contrast, urinary lactulose/rhamnose ratio after indomethacin ingestion plus ATP administration [0.027 (0.020–0.046)] was significantly lower than the lactulose/rhamnose ratio in the placebo condition (P<0.01).

Conclusions Topical ATP administration into the small intestine during short-term challenge of the NSAID indomethacin attenuates the NSAID-induced increase in small intestinal permeability in healthy humans.

aDepartment of Epidemiology, Maastricht University, Nutrition and Toxicology Research Institute Maastricht

bDepartment of Clinical Dietetics/Gastroenterology, Internal Medicine, University Hospital Maastricht, Nutrition and Toxicology Research Institute Maastricht

cDepartment of Gastroenterology, Internal Medicine, Maastricht University, Nutrition and Toxicology Research Institute Maastricht

dDepartment of Pharmacology and Toxicology, Maastricht University, Nutrition and Toxicology Research Institute Maastricht, Maastricht, The Netherlands

Correspondence to Martijn Bours, MSc, Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands

Tel: +31433882903; fax: +31433884128; e-mail:

Received 22 February 2006 Accepted 19 September 2006

© 2007 Lippincott Williams & Wilkins, Inc.