An investigation into the effect and mechanisms of action of nicotine in inflammatory bowel disease

Sykes, Akilah; Brampton, Christopher; Klee, Sabine; Chander, C. L.; Whelan, C. J.; Parsons, Marie J.

doi:10.1007/s000110050597

Cited by 65 publications

(40 citation statements)

References 24 publications

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“…Exacerbation of the DAI score at high doses of nicotine was not observed in s.c. or minipump nicotine-treated animals, suggesting a differential effect of nicotine dose and delivery on colonic inflammation. The results suggesting the protective effects of low-dose nicotine added to the drinking water were similar to those reported in various experimental colitis models in rats and mice (Qiu et al, 1997;Eliakim et al, 1998;Sykes et al, 2000;Ghia et al, 2006). Qiu et al (1997) demonstrated that a 5-mg/ml dose of nicotine in the drinking water in 2,4-dinitrobenzene sulfonic acid (DNBS)-treated rats resulted in a significant decrease in intestinal inflammation; however, the inflammation was shown to increase at a dose of 50 mg/ml.…”

Section: Discussionsupporting

confidence: 85%

“…Qiu et al (1997) demonstrated that a 5-mg/ml dose of nicotine in the drinking water in 2,4-dinitrobenzene sulfonic acid (DNBS)-treated rats resulted in a significant decrease in intestinal inflammation; however, the inflammation was shown to increase at a dose of 50 mg/ml. Similarly, Eliakim et al (1998) and Sykes et al (2000) reported that nicotine had a dual effect on colitis in mice, with low doses of nicotine being more effective at reducing the inflammation than higher doses. This dual anti-inflammatory effect of nicotine in the form of an "inverted-U" was described previously (Picciotto, 2003).…”

Section: Discussionmentioning

confidence: 93%

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

AlSharari

Akbarali

Abdullah

et al. 2012

J Pharmacol Exp Ther

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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-a 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-a. 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.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 93%

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

AlSharari

Akbarali

Abdullah

et al. 2012

J Pharmacol Exp Ther

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“…Nicotine suppresses inflammation during experimental ulcerative colitis (22), improves survival during experimental sepsis via its effect on the production of proinflammatory mediators (23), and blocks leukocyte recruitment in vivo (24). Nicotine suppresses TNF production by LPS-stimulated macrophages (25) and microglial cells (26) through the alpha7 nicotinic acetylcholine receptor (α7nAChR), and inhibits endothelial cell activation in vitro and in vivo (24).…”

Section: Introductionmentioning

confidence: 99%

Nicotine Inhibits Cytokine Production by Placenta Cells via NFκB: Potential Role in Pregnancy-Induced Hypertension

Dowling

Rochelson

Way

et al. 2007

Mol Med

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“…Indeed, a preliminary study suggests that DSS-induced colitis is more severe in mice deficient in nicotinic receptors (28). Although part of the beneficial effect of nicotine is presumably due to its immunosuppressive properties (41,47), cholinergic events that are tilted in favor of absorption, rather than secretion, would be expected to alleviate some of the diarrhea experienced by patients with ulcerative colitis. The present study was designed to further define the mechanism of altered ion transport in the colon of mice with DSS-induced colitis and has revealed a novel pathway involving nicotinic-nitrigeric communication and, possibly, participation by enteric glial cells in the cholinergic control of ion transport.…”

mentioning

confidence: 99%

Dextran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO

Green¹,

Ho²,

Sharkey³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Dextran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO. Am J Physiol Gastrointest Liver Physiol 287: G706 -G714, 2004. First published April 15, 2004 10.1152/ajpgi.00076.2004.-In normal colon, ACh elicits a luminally directed Cl Ϫ efflux from enterocytes via activation of muscarinic receptors. In contrast, in the murine model of dextran sodium sulfate (DSS)-induced colitis, an inhibitory cholinergic ion transport event due to nicotinic receptor activation has been identified. The absence of nicotinic receptors on enteric epithelia and the ability of nitric oxide (NO) to modulate ion transport led us to hypothesize that NO mediated the cholinergic nicotinic receptor-induced changes in ion transport. Midportions of colon from control and DSS-treated mice were examined for inducible NO synthase (iNOS) expression by RT-PCR and immunofluorescence or mounted in Ussing chambers for assessment of cholinergic-evoked changes in ion transport (i.e., shortcircuit current) with or without pretreatment with pharmacological inhibitors of NO production. iNOS mRNA and protein levels were increased throughout the tissue from DSS-treated mice and, notably, in the myenteric plexus, where the majority of iNOS immunoreactivity colocalized with the enteric glial cell marker glial fibrillary acidic protein. The drop in short-circuit current evoked by the cholinomimetic carbachol in tissue from DSS-treated mice was prevented by selective inhibitors of iNOS activity {N 6 -(1-iminoethyl)-lysine HCl and N- [3-(aminomethyl)benzyl]acetamidine} or an NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] or by removal of the myenteric plexus. Thus, in this model of colitis, a "switch" occurs from muscarinic to nicotinic receptor-dominated control of cholinergic ion transport. The data indicate a novel pathway involving activation of nicotinic receptors on myenteric neurons, resulting in release of NO from neurons or enteric glia and, ultimately, a dampening of stimulated epithelial Cl Ϫ secretion that would reduce secretory diarrhea.short-circuit current; chloride; inflammatory bowel disease WATER MOVEMENT between the gut lumen and the interstitium is critically important for hydrating the surface of the enteric epithelium, providing the medium for contact digestion and nutrient absorption, and reducing the contact of pathogens and potentially noxious bacterial or environmental toxins with the enterocytes. This key function of the epithelium is accomplished by the coordinated activity of ion channels, cotransporters, and energy-dependent ion pumps that are asymmetrically arranged in the cell membrane of the polarized epithelium: this allows for vectorial ion transport, creating the driving forces for directed water movements (2). Many intrinsic and extrinsic agents influence epithelial ion transport, including neurotransmitters (e.g., ACh), biogenic amines, nu-

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An investigation into the effect and mechanisms of action of nicotine in inflammatory bowel disease

Cited by 65 publications

References 24 publications

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

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

Nicotine Inhibits Cytokine Production by Placenta Cells via NFκB: Potential Role in Pregnancy-Induced Hypertension

Dextran sodium sulfate-induced colitis reveals nicotinic modulation of ion transport via iNOS-derived NO

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