Limits...
Rivastigmine alleviates experimentally induced colitis in mice and rats by acting at central and peripheral sites to modulate immune responses.

Shifrin H, Nadler-Milbauer M, Shoham S, Weinstock M - PLoS ONE (2013)

Bottom Line: These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg.Co-administration of rivastigmine (1 mg/kg) with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone.The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Institute of Drug Research, Hebrew University Medical Center, Jerusalem, Israel.

ABSTRACT
The cholinergic anti-inflammatory system and α7 nicotinic receptors in macrophages have been proposed to play a role in neuroimmunomodulation and in the etiology of ulcerative colitis. We investigated the ability of a cholinesterase (ChE) inhibitor rivastigmine, to improve the pathology of ulcerative colitis by increasing the concentration of extracellular acetylcholine in the brain and periphery. In combination with carbachol (10 µM), rivastigmine (1 µM) significantly decreased the release of nitric oxide, TNF-α, IL-1β and IL-6 from lipopolysaccharide-activated RAW 264.7 macrophages and this effect was abolished by α7 nicotinic receptor blockade by bungarotoxin. Rivastigmine (1 mg/kg) but not (0.5 mg/kg), injected subcutaneously once daily in BALB/c mice with colitis induced by 4% dextran sodium sulphate (DSS), reduced the disease activity index (DAI) by 60% and damage to colon structure. Rivastigmine (1 mg/kg) also reduced myeloperoxidase activity and IL-6 by >60%, and the infiltration of CD11b expressing cells by 80%. These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg. Co-administration of rivastigmine (1 mg/kg) with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone. Rivastigmine 1 and 2 mg given rectally to rats with colitis induced by rectal administration of 30 mg dintrobezene sulfonic acid (DNBS) also caused a dose related reduction in ChE activity in blood and colon, the number of ulcers and area of ulceration, levels of TNF-α and in MPO activity. The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh. These include ACh released from vagal nerve endings that activates alpha7 nicotinic receptors on circulating macrophages and in brainstem neurons.

Show MeSH

Related in: MedlinePlus

α-bungarotoxin inhibits effect of rivastigmine and carbachol on release of NO in LPS-activated macrophages.Data represents mean ± SEM of 2 independent experiments performed in eight replicates for each sample. Significantly different from LPS alone *p<0.05, **p<0.01; significantly different from macrophages pretreated with rivastigmine+carbachol; # p<0.05.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585220&req=5

pone-0057668-g002: α-bungarotoxin inhibits effect of rivastigmine and carbachol on release of NO in LPS-activated macrophages.Data represents mean ± SEM of 2 independent experiments performed in eight replicates for each sample. Significantly different from LPS alone *p<0.05, **p<0.01; significantly different from macrophages pretreated with rivastigmine+carbachol; # p<0.05.

Mentions: Carbachol (10 µM) and rivastigmine (1 µM) applied individually did not cause any significant reduction in pro-inflammatory cytokines. A combination of rivastigmine (1 µM) with carbachol (10 µM) reduced TNF-α and IL-6 by 50% and 46%, respectively. The steroid budesonide (100 nM) reduced the level TNF-α by 90% and IL-6 by 80% (Figures 1B and C). Pre-incubation with α-bungarotoxin antagonized the effect of rivastigmine plus carbachol in a dose-related manner (Figure 2).


Rivastigmine alleviates experimentally induced colitis in mice and rats by acting at central and peripheral sites to modulate immune responses.

Shifrin H, Nadler-Milbauer M, Shoham S, Weinstock M - PLoS ONE (2013)

α-bungarotoxin inhibits effect of rivastigmine and carbachol on release of NO in LPS-activated macrophages.Data represents mean ± SEM of 2 independent experiments performed in eight replicates for each sample. Significantly different from LPS alone *p<0.05, **p<0.01; significantly different from macrophages pretreated with rivastigmine+carbachol; # p<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585220&req=5

pone-0057668-g002: α-bungarotoxin inhibits effect of rivastigmine and carbachol on release of NO in LPS-activated macrophages.Data represents mean ± SEM of 2 independent experiments performed in eight replicates for each sample. Significantly different from LPS alone *p<0.05, **p<0.01; significantly different from macrophages pretreated with rivastigmine+carbachol; # p<0.05.
Mentions: Carbachol (10 µM) and rivastigmine (1 µM) applied individually did not cause any significant reduction in pro-inflammatory cytokines. A combination of rivastigmine (1 µM) with carbachol (10 µM) reduced TNF-α and IL-6 by 50% and 46%, respectively. The steroid budesonide (100 nM) reduced the level TNF-α by 90% and IL-6 by 80% (Figures 1B and C). Pre-incubation with α-bungarotoxin antagonized the effect of rivastigmine plus carbachol in a dose-related manner (Figure 2).

Bottom Line: These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg.Co-administration of rivastigmine (1 mg/kg) with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone.The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Institute of Drug Research, Hebrew University Medical Center, Jerusalem, Israel.

ABSTRACT
The cholinergic anti-inflammatory system and α7 nicotinic receptors in macrophages have been proposed to play a role in neuroimmunomodulation and in the etiology of ulcerative colitis. We investigated the ability of a cholinesterase (ChE) inhibitor rivastigmine, to improve the pathology of ulcerative colitis by increasing the concentration of extracellular acetylcholine in the brain and periphery. In combination with carbachol (10 µM), rivastigmine (1 µM) significantly decreased the release of nitric oxide, TNF-α, IL-1β and IL-6 from lipopolysaccharide-activated RAW 264.7 macrophages and this effect was abolished by α7 nicotinic receptor blockade by bungarotoxin. Rivastigmine (1 mg/kg) but not (0.5 mg/kg), injected subcutaneously once daily in BALB/c mice with colitis induced by 4% dextran sodium sulphate (DSS), reduced the disease activity index (DAI) by 60% and damage to colon structure. Rivastigmine (1 mg/kg) also reduced myeloperoxidase activity and IL-6 by >60%, and the infiltration of CD11b expressing cells by 80%. These effects were accompanied by significantly greater ChE inhibition in cortex, brain stem, plasma and colon than that after 0.5 mg/kg. Co-administration of rivastigmine (1 mg/kg) with the muscarinic antagonist scopolamine significantly increased the number of CD11b expressing cells in the colon but did not change DAI compared to those treated with rivastigmine alone. Rivastigmine 1 and 2 mg given rectally to rats with colitis induced by rectal administration of 30 mg dintrobezene sulfonic acid (DNBS) also caused a dose related reduction in ChE activity in blood and colon, the number of ulcers and area of ulceration, levels of TNF-α and in MPO activity. The study revealed that the ChE inhibitor rivastigmine is able to reduce gastro-intestinal inflammation by actions at various sites at which it preserves ACh. These include ACh released from vagal nerve endings that activates alpha7 nicotinic receptors on circulating macrophages and in brainstem neurons.

Show MeSH
Related in: MedlinePlus