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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Novel Insights on the Effect of Nicotine in a Murine Colitis Model

Shakir D. AlSharari, Hamid I. Akbarali, Rehab A. Abdullah, Omer Shahab, Wimolnut Auttachoat, Gabriela A. Ferreira, Kimber L. White, Aron H. Lichtman, Guy A. Cabral and M. Imad Damaj
Journal of Pharmacology and Experimental Therapeutics January 2013, 344 (1) 207-217; DOI: https://doi.org/10.1124/jpet.112.198796
Shakir D. AlSharari
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Hamid I. Akbarali
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Rehab A. Abdullah
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Omer Shahab
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Wimolnut Auttachoat
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Gabriela A. Ferreira
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Kimber L. White
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Aron H. Lichtman
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Guy A. Cabral
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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M. Imad Damaj
Department of Pharmacology and Toxicology (S.D.A., H.I.A., R.A.A., O.S., K.L.W., A.H.L., M.I.D.) and Department of Microbiology and Immunology (W.A., G.A.F, G.A.C.), Virginia Commonwealth University, Richmond, Virginia
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Abstract

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.

Footnotes

  • This work was supported by National Institutes of Health [Grants DA-019377 (to M.I.D.) and DK 046367] (to H.I.A.).

  • dx.doi.org/10.1124/jpet.112.198796.

  • Received July 25, 2012.
  • Accepted October 29, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 344 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 344, Issue 1
1 Jan 2013
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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Effect of Nicotine in a Murine Colitis Model

Shakir D. AlSharari, Hamid I. Akbarali, Rehab A. Abdullah, Omer Shahab, Wimolnut Auttachoat, Gabriela A. Ferreira, Kimber L. White, Aron H. Lichtman, Guy A. Cabral and M. Imad Damaj
Journal of Pharmacology and Experimental Therapeutics January 1, 2013, 344 (1) 207-217; DOI: https://doi.org/10.1124/jpet.112.198796

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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Effect of Nicotine in a Murine Colitis Model

Shakir D. AlSharari, Hamid I. Akbarali, Rehab A. Abdullah, Omer Shahab, Wimolnut Auttachoat, Gabriela A. Ferreira, Kimber L. White, Aron H. Lichtman, Guy A. Cabral and M. Imad Damaj
Journal of Pharmacology and Experimental Therapeutics January 1, 2013, 344 (1) 207-217; DOI: https://doi.org/10.1124/jpet.112.198796
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