The effect of N-acetylcysteine on chloride efflux from airway epithelial cells

Cell Biol Int. 2010 Jan 27;34(3):245-52.

The effect of N-acetylcysteine on chloride efflux from airway epithelial cells.

Varelogianni G, Oliynyk I, Roomans GM, Johannesson M.

Source

Department of Medical Cell Biology, Uppsala University, Box 571, SE-75123 Uppsala, Sweden. georgia.varelogianni@orebroll.se

Abstract

Defective chloride transport in epithelial cells increases mucus viscosity and leads to recurrent infections with high oxidative stress in patients with CF (cystic fibrosis). NAC (N-acetylcysteine) is a well known mucolytic and antioxidant drug, and an indirect precursor of glutathione. Since GSNO (S-nitrosoglutathione) previously has been shown to be able to promote Cl- efflux from CF airway epithelial cells, it was investigated whether NAC also could stimulate Cl- efflux from CF and non-CF epithelial cells and through which mechanisms. CFBE (CF bronchial epithelial cells) and normal bronchial epithelial cells (16HBE) were treated with 1 mM, 5 mM, 10 mM or 15 mM NAC for 4 h at 37 degrees C. The effect of NAC on Cl- transport was measured by Cl- efflux measurements and by X-ray microanalysis. Cl- efflux from CFBE cells was stimulated by NAC in a dose-dependent manner, with 10 mM NAC causing a significant increase in Cl- efflux with nearly 80% in CFBE cells. The intracellular Cl- concentration in CFBE cells was significantly decreased up to 60% after 4 h treatment with 10 mM NAC. Moreover immunocytochemistry and Western blot experiments revealed expression of CFTR channel on CFBE cells after treatment with 10 mM NAC. The stimulation of Cl- efflux by NAC in CF airway epithelial cells may improve hydration of the mucus and thereby be beneficial for CF patients.

Day 2 - Kalydeco

Well, suffice it to say that I feel a bit like I'm flashing back to Fall 2006, about 5 1/2 years ago, when I first started taking NAC. (http://noexcusesnoexcuses.blogspot.com/2008/08/nac.html)

It's true, we look for little signs of medication working or for side effects particularly right when we start something new. I took my first dose of Kalydeco right before bed on 3/9 Friday. Here is what I observed:

• Prior to starting Kalydeco, I had been a bit non-compliant with my green smoothies and felt quite a bit more tight and non-moving mucus-y in my right middle lobe. I would cough but nothing would come up - but I could tell it was there. My FEV1 on 3/5 at clinic was 80%

• When I woke up yesterday (3/10) AM, the first thing I noticed was how clear my sinuses felt. I could feel air moving in my sinuses where I feel like I've never felt air move before. Like up above my eyebrows - it was almost distracting because it was so different and weird

• I coughed up pretty watery, much thinner than what I had the past few day's mucus. My right middle lobe felt much clearer

• I have kind of avoided exercising the past few weeks because it was so exhausting to cough so much - but exercising yesterday was much easier and I could breathe deeper in my right middle lobe. I coughed while exercising but it was mostly a dry cough

• Today I don't notice as much air flowing through my sinuses, but it's possible that I'm used to it or it was just a fluke yesterday. Not sure

• I for sure have a plug stuck in my right middle lobe and it's a bit harder for me to breathe in my right lobe today. I am going to try to go for a run later today to cough it up (that usually does the trick) - it will be cool to see how my endurance is

• I had another feminine side effect that normally I would post here because I'm comfortable posting anything - but I realize that all my readers might not be comfortable reading all I feel to share. Ha. So if you're curious, drop me an email or a PM and I'll fill you in :)

So all in all, some changes that I am cautiously optimistic about. It may be complete placebo effect, but that's fine with me - I feel good, whatever the cause. 

I'll continue to keep you guys posted

1st Kalydeco dose

I was very fortunate and blessed to get my 1st Kalydeco dose in the mail today.

Luckily my doc was willing to give it a try, even though I don't have G551D (I have DF508 and Di507). And my insurance covered Kaly for a really reasonable co-pay.

I'm really not expecting it to do much, but I figured it most likely won't hurt me so I should just give it a shot.

There are so many things that can influence how genes are expressed, such as modifier genes, exercise (Stanford states that exercising actually increases CFTR function) and the foods we eat. So I think our CF genes don't tell the whole story - another reason why just trying Kaly is a good idea in my mind.

I look forward to keeping you all posted on my progress or lack thereof over the next month(s).

Update so far is that I took my 1st Kaly at around 9pm with my dear friend and parents watching me over video chat.

Bottom's up!

According to Vertex: "In recombinant cells VX-770 increased CFTR channel open probability (P(o)) in both the F508del processing mutation and the G551D gating mutation."

http://www.ncbi.nlm.nih.gov/pubmed/19846789

From Annals of Human Genetics, 2003, by Rowntree et al,:

"Measurements of Cl- conductase of intestine and respiratory tissues of DF508 homozygote CF patients suggest, in vivo, that at least some DF508 CFTR can reach the plasma membrane"

http://www.colorado.edu/MCDB/MCDB4600/1ReviewPhenotype.pdf