In vivo influence of nicotine on human basal and NSAID-induced gut barrier function

Scand J Gastroenterol. 2003 Apr;38(4):399-408. doi: 10.1080/00365520310000834.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Biomarkers
  • Carbohydrates / pharmacokinetics
  • Chromium Radioisotopes / urine*
  • Drug Synergism
  • Female
  • Humans
  • Indomethacin / pharmacokinetics*
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Lactulose / urine
  • Male
  • Middle Aged
  • Nicotine / pharmacokinetics*
  • Nicotinic Agonists / pharmacokinetics*
  • Permeability / drug effects
  • Sucrose / analogs & derivatives*
  • Sucrose / urine

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Carbohydrates
  • Chromium Radioisotopes
  • Nicotinic Agonists
  • Lactulose
  • Sucrose
  • Nicotine
  • trichlorosucrose
  • Indomethacin