Novel insights on the effect of nicotine in a murine colitis model

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 344; no. 1; pp. 207 - 217
• Main Authors: AlSharari, Shakir D, Akbarali, Hamid I, Abdullah, Rehab A, Shahab, Omer, Auttachoat, Wimolnut, Ferreira, Gabriela A, White, Kimber L, Lichtman, Aron H, Cabral, Guy A, Damaj, M Imad
• Format: Journal Article
• Language: English
• Published: United States The American Society for Pharmacology and Experimental Therapeutics 01.01.2013
• Subjects: Animals; Chromatography, High Pressure Liquid; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - pathology; Colon - pathology; Cotinine - blood; Cotinine - pharmacology; Dextran Sulfate; Dose-Response Relationship, Drug; Gastrointestinal, Hepatic, Pulmonary, and Renal; Inflammation - pathology; Infusions, Intravenous; Injections, Subcutaneous; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Nicotine - administration & dosage; Nicotine - blood; Nicotine - therapeutic use; Nicotinic Agonists - administration & dosage; Nicotinic Agonists - blood; Nicotinic Agonists - therapeutic use; Peroxidase - metabolism; Smoking; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.112.198796

Studies showed that nicotine has a positive influence on symptoms of ulcerative colitis. In the present study, we explored the effect of nicotine treatment using different routes of administration in the dextran sodium sulfate (DSS) colitis mouse model. We also investigated the effects of cotinine, a major metabolite of nicotine, in the model. C57BL6 adult male mice were given DSS solution freely in the drinking water for seven consecutive days, and tap water was given thereafter. Disease severity, length of the colon, colon tissue histology, and inflammatory markers, including colonic myeloperoxidase activity and colonic tumor necrosis factor-α levels, were evaluated. The effect of nicotine and cotinine treatments via various different routes of administration were examined the DSS model. In addition, we measured the plasma levels of nicotine and cotinine in our treatment protocols. Administration of low, but not high, doses of oral nicotine in DSS-treated mice resulted in a significant decrease in disease severity, histologic damage scores, as well as colonic level of tumor necrosis factor-α. However, the anti-inflammatory effect of nicotine was not seen after chronic s.c. or minipump infusion of the drug. Differences in plasma levels of nicotine and cotinine do not seem to account for this lack of effect. Finally, oral cotinine alone failed to show a significant effect in the DSS model of colitis. These results highlight that dose and route of administration play a critical role in the protective effect of nicotine in the DSS mouse colitis model.