In vivo influence of nicotine on human basal and NSAID-induced gut barrier function.
BACKGROUND
Smoking reduces the non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal permeability increase in healthy people. It also affects inflammatory bowel disease that is associated with a disturbed gut barrier function. To assess the role of nicotine on barrier function, its influence on basal and NSAID-induced intestinal permeability was studied in healthy volunteers.


METHODS
Thirty-one healthy non-smoker subjects performed permeability tests with 51Cr-EDTA and sugar markers (sucrose, lactulose, mannitol, sucralose) before and during 2 weeks of nicotine patch application, and with and without indomethacin intake, respectively. Since smoking has been described as affecting motility, transit measurements were also done with the sodium[13C]-octanoate and lactose-[13C]-ureide breath tests before and during nicotine exposure. Correlations between permeability markers were checked and the influence of gastrointestinal transit was assessed.


RESULTS
Nicotine did not affect barrier function in vivo, nor gastric emptying, small-bowel transit time or orocaecal transit. 51Cr-EDTA and lactulose correlated in basal 0-6 h permeability testing (r = 0.529, P < 0.0001), as did 6-24 h excretion of 51Cr-EDTA and sucralose (r = 0.474, P < 0.001); 97% and 90% of the subjects had a permeability increase after indomethacin intake for 0-6 h and 6-24 h excretion of Cr-EDTA, respectively. This population proportion is 63% for lactulose/mannitol and 83% for sucralose.


CONCLUSIONS
Short-term exposure to nicotine does not alter normal basal or NSAID-induced gut barrier function or transit. 51Cr-EDTA and the respective sugar markers correlate well in in vivo permeability testing in healthy humans. The radioactive test detects more NSAID-induced permeability increase than does the lactulose/mannitol ratio permeability test.
Suenaert
P
P
Dept. of Gastroenterology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium.
Bulteel
V
V
Den Hond
E
E
Geypens
B
B
Monsuur
F
F
Luypaerts
A
A
Ghoos
Y
Y
Rutgeerts
P
P
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D015415:Biomarkers; D002241:Carbohydrates / Q000493:pharmacokinetics; D002860:Chromium Radioisotopes / Q000652:urine*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000493:pharmacokinetics*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D007792:Lactulose / Q000652:urine; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000493:pharmacokinetics*; D018722:Nicotinic Agonists / Q000493:pharmacokinetics*; D010539:Permeability / Q000187:drug effects; D013395:Sucrose / Q000031:analogs & derivatives* / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D002241:Carbohydrates; D002860:Chromium Radioisotopes; D018722:Nicotinic Agonists; D007792:Lactulose; D013395:Sucrose; D009538:Nicotine; C026285:trichlorosucrose; D007213:Indomethacin