Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis

Rami Eliakim, Fanny Karmeli, Daniel Rachmilewitz, Petrichia Cohen, Alexander Fich

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Smoking, probably due to nicotine, has a bivalent effect on inflammatory bowel disease, ameliorating disease activity in ulcerative colitis and with a deleterious effect on Crohn's disease. The effect of nicotine patches in ulcerative colitis is controversial. Aim. To investigate the effect of chronic nicotine use in a rat model of colitis. Methods. Colitis was induced in Sprague-Dawley rats by rectal administration of 30 mg trinitrobenzene sulphonic acid (TNBS) in 50% ethanol. Nicotine was dissolved in drinking water (2.5, 12.5, 25 and 250 μg/ml), with rats drinking ad libitum. Nicotine administration started 10 days prior to damage induction and had no effect on weight gain or daily food intake of rats. Rats were sacrificed 1 and 5 days after TNBS administration, their colons resected, rinsed, weighed, damage assessed macroscopically (mm2) and microscopically and tissue processed for myeloperoxidase (MPO) and nitric oxide synthase (NOS) activities, leukotriene B4 (LTB4), prostaglandin E2 (PGE2) generation and interleukin-1 (IL-1) serum levels. Results. Nicotine, by itself, caused no damage to the colon. Nicotine had a dose-dependent bivalent effect on colitis, significantly reducing macroscopic damage from 983 ± 10 mm2 on TNBS alone to 429 ± 118 mm2 on TNBS plus 12.5 μg/ml of nicotine, and escalating to 1086 ± 262 mm2 on 250 μg/ml of nicotine. Segmental weight declined significantly (from 2.4 ± 0.2 to 1.65 ± 0.20 g/10 cm), on 125 μg/ml nicotine, as did MPO activity (from 3.2 ± 0.4 to 0.7 ± 0.1 units/g). All these parameters returned to the levels of TNBS alone when the dose of nicotine was increased to 250 μg/ml. Nicotine had no effect on NOS activity, PGE2 generation and serum IL-1 levels, but increased LT4 generation. Conclusions. Nicotine has a dose-dependent bivalent effect on TNBS-induced colitis which is not due to reduction in IL-1 serum levels or PGE2 generation, and is not NOS-mediated.

Original languageEnglish
Pages (from-to)1013-1019
Number of pages7
JournalEuropean Journal of Gastroenterology and Hepatology
Volume10
Issue number12
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Colitis
  • Interleukin-1
  • Leukotriene B
  • Nicotine
  • Prostaglandin E
  • Trinitrobenzene sulphonic acid

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