Re: Nicotine and gut permeability: the smoking/PSC link clarified

[Guest guest]

Nicotine hasn't protected me from PSC or UC. I've been a smoker for a long

time (decades). For about 7 years now I've been chewing nicorette gum

instead of smoking, and it's during that time that the PSC has reared its

ugly head. I'm weaning myself off the gum now (for financial reasons - the

gum is very expensive). I'll let you know if the PSC gets worse.

-Marie

>

>Cullen and Chapman (2001) have proposed that " PSC may be triggered in

>genetically susceptible individuals by toxic or infectious agents

>gaining access to the liver via a diseased and permeable colon "

>(Cullen S, Chapman R 2001 Aetiopathogenesis of primary sclerosing

>cholangitis. Best Pract. Res. Clin. Gastroenterol. 15: 577-589).

>

>Smoking seems to be protective against both UC and PSC ( " PSC, like

>UC, is a disease of non-smokers as the odds of having PSC was

>significantly decreased among current and former smokers " [

>SA, Thyssen M, Orchard TR, Jewell DP, Fleming KA, Chapman RW 2002

>Cigarette smoking, appendectomy, and tonsillectomy as risk factors

>for the development of primary sclerosing cholangitis: a case control

>study. Gut 51: 567-573]).

>

>Does this imply that smoking somehow reduces the permeability of the

>colon? A recent study now sheds some light on this question ... it

>seems that nicotine does indeed reduce gut permeability by increasing

>expression of tight junction proteins:

>

>Food Chem Toxicol. 2007 Feb 24; [Epub ahead of print]

>

>The effect of nicotine in vitro on the integrity of tight junctions

>in Caco-2 cell monolayers.

>

>McGilligan VE, Wallace JM, Heavey PM, Ridley DL, Rowland IR

>

>Northern Ireland Centre for Food and Health (NICHE), Biomedical

>Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland,

>UK.

>

>Ulcerative colitis is characterised by impairment of the epithelial

>barrier and tight junction alterations resulting in increased

>intestinal permeability. UC is less common in smokers with smoking

>reported to decrease paracellular permeability. The aim of this study

>was thus to determine the effect of nicotine, the major constituent

>in cigarettes and its metabolites on the integrity of tight junctions

>in Caco-2 cell monolayers. The integrity of Caco-2 tight junctions

>was analysed by measuring the transepithelial electrical resistance

>(TER) and by tracing the flux of the fluorescent marker fluorescein,

>after treatment with various concentrations of nicotine or nicotine

>metabolites over 48h. TER was significantly higher compared to the

>control for all concentrations of nicotine 0.01-10muM at 48h

>(p<0.001), and for 0.01muM (p<0.001) and 0.1muM and 10muM nicotine

>(p<0.01) at 12 and 24h. The fluorescein flux results supported those

>of the TER assay. TER readings for all nicotine metabolites tested

>were also higher at 24 and 48h only (p0.01). Western blot analysis

>demonstrated that nicotine up-regulated the expression of the tight

>junction proteins occludin and claudin-1 (p0.01). Overall, it appears

>that nicotine and its metabolites, at concentrations corresponding to

>those reported in the blood of smokers, can significantly improve

>tight junction integrity, and thus, decrease epithelial gut

>permeability. We have shown that in vitro, nicotine appears more

>potent than its metabolites in decreasing epithelial gut

>permeability. We speculate that this enhanced gut barrier may be the

>result of increased expression of claudin-1 and occludin proteins,

>which are associated with the formation of tight junctions. These

>findings may help explain the mechanism of action of nicotine

>treatment and indeed smoking in reducing epithelial gut permeability.

>PMID: 17399881.

>

>This seems to be a good explanation for the protective effect of

>smoking/nicotine on UC and PSC, and begins to clear up one mystery

>about UC/PSC.

>

>Dave

>(father of (21); PSC 07/03; UC 08/03)

>

>

>

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[Guest guest]

Interesting Dave,Should I be getting Bill some nicotine gum?? Or a nicotine patch?I need to look up the side effects of nicotine because experimenting with smoking is not an option.LeeSmoking seems to be protective against both UC and PSC ("PSC, like UC, is a disease of non-smokers as the odds of having PSC was significantly decreased among current and former smokers" [ SA, Thyssen M, Orchard TR, Jewell DP, Fleming KA, Chapman RW 2002 Cigarette smoking, appendectomy, and tonsillectomy as risk factors for the development of primary sclerosing cholangitis: a case control study. Gut 51: 567-573]).Does this imply that smoking somehow reduces the permeability of the colon? A recent study now sheds some light on this question ... it seems that nicotine does indeed reduce gut permeability by increasing expression of tight junction proteins:

[Guest guest]

Well, I guess that answers my chewing gum question !!

Lee

>

>

> Nicotine hasn't protected me from PSC or UC. I've been a smoker for

> a long

> time (decades). For about 7 years now I've been chewing nicorette gum

> instead of smoking, and it's during that time that the PSC has

> reared its

> ugly head. I'm weaning myself off the gum now (for financial

> reasons - the

> gum is very expensive). I'll let you know if the PSC gets worse.

>

> -Marie

>

[Guest guest]

I seem to remember a study on smoking which concluded that smoking after

PSC had already developed was not helpful, and was in fact a risk factor

for developing CCA.

When I first heard about the link I thought about whether I'd use

nicotine if it was shown to help, but so far I haven't had to make the

decision, because the risk/benefit ratio isn't there for me (to put it

mildly!)

athan