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Inhaled Resveratrol


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#1 Aer O'Head

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Posted 06 September 2010 - 01:03 PM


I'd like to introduce myself to the group as a COPD patient of the emphysema variety. My primary interest in resveratrol is from that angle, as there's a significant body of research regarding its effects on pulmonary oxidative stress, inflammation and accelerated apoptosis. These, of course, are at the very root of the characteristic -- and inevitable -- progression of the disease. SIRT1, HDAC2, NF-κB, AP-1 and Nrf2 all play major roles in this. (As they do in lung cancer, to which COPD patients are many times more susceptible than others because of these very same factors.)

I've ordered some of the micronized bulk powder resveratrol. I've familiarized myself with most of the available literature on bioavailability issues and delivery techniques, which are my main concern at the moment. That includes having scoured this forum for posts on the subject. As far as my reading goes, it would appear that the most promising techniques are buccal mucosa and/or liposomal. However, since I already nebulize reduced glutathione, I've wondered from the start about the safety and efficacy of inhaling pure and micronized resveratrol, either in a nebulized solution or as a dry powder via a device such a RotaHaler. There is a distinct lack of research material to be found on this. I found only one (favorable) study of inhaled resveratrol in mice, and several references to inhaled resveratrol being a promising area of research, but that's about it. It's worth mentioning that one of the leading researchers in the field, Prof. Peter J. Barnes, has shown interest in this area. Indeed, he's obtained at least one or two resveratrol related patents. It should be obvious that I seek to avoid the liver and intestines and directly target the pulmonary epithelium.

So I'd like to ask for the group's help in exploring this topic, as I seem to have exhausted my resources. Any possible leads, thoughts or even just speculative comments will be appreciated. I should probably mention that in addition to the nebulized glutathione, N-acetylcysteine, curcumin, sulforaphane, etc. play major roles in my regimen. I eagerly look forward to hearing your thoughts on this question.

#2 2tender

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Posted 06 September 2010 - 03:57 PM

Its certainly not something I would try unless; I could obtain a Physicians supervision and 100% pure synthetic Resveratrol. I think you could obtain the same level of benefit, albeit in a longer time frame via regular oral ingestion. The idea of nebulizing anything extracted from plant matter, that isnt 100% pure doesnt appeal to me. Is your glutathione pharmaceutical and intended to be used that way? The idea of just buying some bulk powder and inhaling it without a Doctors okay or supervision doesnt sound prudent, unless, of course, I was a physician and had the medical resources on hand, as in a hospital setting, to allay any potential sides. Im sure someone will chime in on this.

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#3 Anthony_Loera

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Posted 06 September 2010 - 11:16 PM

The solubility issue with resveratrol alone, would prevent me from considering it... unless you have some dry nano-resveratrol?

As soon as you take it though... it would not be considered a supplement, according to the FDA. Don't think this will be available anytime soon because of it.

Not many people have dry nano-res.

A

#4 niner

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Posted 07 September 2010 - 12:18 AM

I'm not too crazy about the inhalation of pure resveratrol, due to the solubility issue. I would be concerned that it might form an insoluble mass in the alveoli. One thing that comes to mind is a cyclodextrin complex. These are water soluble and could be nebulized. What sort of markers would you look at to see if it was working? FEV1? This is going beyond mere cutting edge medicine; pretty much uncharted territory. Is there any way to do an animal experiment?

#5 Anthony_Loera

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Posted 07 September 2010 - 01:11 AM

I would be concerned that it might form an insoluble mass in the alveoli. One thing that comes to mind is a cyclodextrin complex.


Yup, I agree with you... however, the cyclodesxtrin complex we have made is about 5-10% res, while most of it is cyclodextrin. Tastes awful, and it was for research purposes only.

If someone would provide it through a local 'lab' ... I am not sure you want to inhale 90% cyclodextrins either, heck I wouldn't.

A

#6 Aer O'Head

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Posted 07 September 2010 - 02:56 AM

Many thanks to all for your interest and comments. I'm gratified by the response to my post.

It seems that the main concern expressed is that of solubility. I've wondered about that as well. For one thing, the nebulizer (whether jet or ultrasonic; I have both) generates a certain amount of agitation and vibration. We're talking about roughly 2 cc of solution, which can be nebulized in a matter of minutes. My guess is that the vibration, accompanied by additional shaking and swirling if necessary, would be sufficient to keep the resveratrol in suspension, if not exactly dissolved. There's also the option of dry powder inhalation, which might even be preferable for several reasons, not least convenience. Prof. Barnes discusses these and other methods, albeit somewhat speculatively, in his patent #6,878,751

The study I mentioned earlier is "Effect of resveratrol on chronic obstructive pulmonary disease in rats and its mechanism" (PMID 18507337). I don't have access to the actual paper for the specific details, but the abstract (quoted below) states that "The results showed that atomization inhaled resveratrol could alleviate rat COPD lung injury accompanied by amelioration of pathological changes." It would be interesting to see the full paper for a description of their methods and formulations. (The article is in Chinese, but my qigong sifu is a native and could easily translate for me if I could locate a copy.)

I've sent Prof. Barnes an email requesting more information, but I've been informed that he's away until the middle of the month. In the meanwhile, I very much appreciate the discussion here!


[Effect of resveratrol on chronic obstructive pulmonary disease in rats and its mechanism]

[Article in Chinese]

Zhou M, He JL, Yu SQ, Zhu RF, Lu J, Ding FY, Xu GL.

Center of New Drug Research and Development, Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.

Abstract

The purpose of this study is to establish COPD animal model by intra-tracheal instillation of bleomycin (BLM) once and exposure to cigarette smoke for continuous 27 d, and to observe the effects of the inhalation on the model. At the 29th day, blood samples were taken from cervical artery for blood-gas analysis and parameters of lung function were recorded. Bronchoalveolar lavage fluid (BALF) was collected to measure intercellular adhesion molecule-1 (ICAM-1) concentration. The results showed that atomization inhaled resveratrol could alleviate rat COPD lung injury accompanied by amelioration of pathological changes, increase the ratio of forced expiratory volume in 0.3 s (FEV0.3) and forced vital capacity (FVC), and decrease the ICAM-1 level in BALF. The ultimate reduction of inflammatory factors was involved, at least in part, in the mechanism of resveratrol effects.

PMID: 18507337 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....pubmed/18507337

#7 maxwatt

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Posted 07 September 2010 - 09:51 PM

I believe lipid solubility of resveratrol would be an important factor for its bioavailability by this method. THC in marijuana is very fat-soluble, which contributes to efficient absorption on inhalation of the smoke. Resveratrol is not as lipid soluble, if I recall, so the efficiency might be less than desired. Use of a vaporizer might work, or resveratrol might decompose on exposure to heat; one study found cooking at 300 degrees Fahrenheit for 30 minutes reduced the content of resveratrol-spiked muffins by about 50%.

This is uncharted territory.

#8 Aer O'Head

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Posted 08 September 2010 - 12:39 PM

I'm afraid you may have gotten the wrong impression somewhere. It might appear as though someone nebulizing is smoking, but that's actually an extremely fine mist, usually very close to room temperature. A "super vaporizer" you might say.

I believe lipid solubility of resveratrol would be an important factor for its bioavailability by this method. THC in marijuana is very fat-soluble, which contributes to efficient absorption on inhalation of the smoke. Resveratrol is not as lipid soluble, if I recall, so the efficiency might be less than desired. Use of a vaporizer might work, or resveratrol might decompose on exposure to heat; one study found cooking at 300 degrees Fahrenheit for 30 minutes reduced the content of resveratrol-spiked muffins by about 50%.



#9 maxwatt

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Posted 09 September 2010 - 03:00 AM

I'm afraid you may have gotten the wrong impression somewhere. It might appear as though someone nebulizing is smoking, but that's actually an extremely fine mist, usually very close to room temperature. A "super vaporizer" you might say.

I believe lipid solubility of resveratrol would be an important factor for its bioavailability by this method. THC in marijuana is very fat-soluble, which contributes to efficient absorption on inhalation of the smoke. Resveratrol is not as lipid soluble, if I recall, so the efficiency might be less than desired. Use of a vaporizer might work, or resveratrol might decompose on exposure to heat; one study found cooking at 300 degrees Fahrenheit for 30 minutes reduced the content of resveratrol-spiked muffins by about 50%.


I missed that you are using a nebulizer; the part about lipid solubility still holds, and I would not recommend inhling oil droplets. Resveratrol does dissolve in water, but poorly: 30 mg per liter. This would be a very weak solution, but might be sufficient for the effects you want.

Edited by maxwatt, 09 September 2010 - 03:09 AM.
more information


#10 2tender

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Posted 09 September 2010 - 04:40 PM

I believe lipid solubility of resveratrol would be an important factor for its bioavailability by this method. THC in marijuana is very fat-soluble, which contributes to efficient absorption on inhalation of the smoke. Resveratrol is not as lipid soluble, if I recall, so the efficiency might be less than desired. Use of a vaporizer might work, or resveratrol might decompose on exposure to heat; one study found cooking at 300 degrees Fahrenheit for 30 minutes reduced the content of resveratrol-spiked muffins by about 50%.

This is uncharted territory.


Purely speculative, and futuristic, first there must be conclusive and consistent studies that verify Resveratrol is beneficial. If Resveratrol was the "Soma" or "The fountain of youth" per se it would be scheduled and everyone that could afford it, would be using it. However, it does seem to do something positive for me, even with irregular dosing..

#11 Aer O'Head

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Posted 12 September 2010 - 02:59 PM

As Hannibal of the A-Team series used to say, "I love it when a plan comes together." My first two experiments didn't quite work out the way I had anticipated. I'm comforted, however, by Einstein's sage comment, "If we knew what it was we were doing, it would not be called research, would it?"

I decided to go with dry powder inhalation first, mainly because of the simplicity and because of the solubility question. I put 250 mg pure micronized trans-resveratrol powder into a RotaHaler device (from Cipla) and took a very deep and forceful inhalation, hoping to get as much as possible into the lower lungs. It took only a split second to realize that it was a failure. The powder stuck to every single surface it encountered, most especially the upper back palate and the back of the throat. I'm guessing that I got at least some benefit through the buccal effect. There was a slight burning sensation at the back of the throat, quite similar to a mild sore throat. I believe that a very small amount (1/8? 1/4?) actually made it into the lungs, as I could feel a slight burning sensation there as well.

This morning, I decided to try the nebulization route. I mixed 250 mg with 5 ml .9% NaCl solution (AddiPak). Throughout, the resveratrol seemed to stay in suspension just fine, making a solution very similar to milk in appearance. Things seem to start okay, but very quickly went south. When things trickled a stop at the mouthpiece, I found that the resveratrol had once again stuck to every available surface, forming something of a paste. I speculated that I might get better results with a different nebulizer kit, as the Pari LC Plus that I was using has an extremely small jet aperture. I switched the remaining contents (after swishing around to try to reclaim the stuck particles) over to a more "generic" kit (Salter 8900). This gave somewhat better results as to throughput (to borrow a computer term), as the flow rate improved and I could feel some effects in my airways. But once again, the resveratrol was sticking on every surface it could find. In short, I cannot even make a good guess as to how much I may have actually inhaled, except to say that it was very little indeed.

I'm now thinking along the lines of working with some sort of mixture. I've come across several references in the literature that I'll need to revisit. There are also some ideas to be found in another paper on the topic that I managed to find, "Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-κB-independent mechanism"(http://www.fasebj.or...4-2691fjev1.pdf).

Regarding Anthony's comment about the FDA not considering this to be a supplement under such circumstances, it should be noted that thousands of people have been nebulizing reduced l-glutathione (a widely available supplement, also referred to as GSH) for at least ten years now. Indeed, it has become something of an accepted respiratory treatment and it is mentioned frequently in the literature. Nevertheless, it has never lost its standing as a supplement. To my knowledge, the FDA has never even questioned this at all. (The supplement itself has FDA GRAS certification.)

Edited by Aer O'Head, 12 September 2010 - 03:01 PM.


#12 maxwatt

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Posted 12 September 2010 - 04:34 PM

Aero - How did they administer resveratrol to the mice in the COPD model you cited in our first post? Do you have full access to the paper and the methods section?

#13 Lufega

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Posted 12 September 2010 - 06:45 PM

Do you have COPD as a result of smoking or because of a genetic disease? I have emphysema from the latter. I've also researched this problem quite a bit but it's the first time I learn about resveratrol helping. NAC has made a big different for me reducing shortness of breath significantly. There is also a body of research pointing to Vitamin A in the form of ATRA can actually regenerated the lung. Have you any info. on this ?

I thought about using nebulized Vitamin A for just this purpose. Can this be done ? I'm also curious about your regimen. I've seem to hit a wall in my research and maybe you can open new areas of interest for me.

#14 Aer O'Head

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Posted 13 September 2010 - 12:05 AM

Aero - How did they administer resveratrol to the mice in the COPD model you cited in our first post? Do you have full access to the paper and the methods section?

I can't find it right offhand ... it's "around here somewhere." Plus, I can't recall if I have the entire paper or just the abstract. I do remember that it was administered intratracheally, so that doesn't help with the inhalation problem. But it stuck in my head because it was my very first clue that direct administration to the pulmonary epithelium was safe and efficacious. At least with rodents ... and at least to some degree. If I spot it again (it's in ONE of these piles!), I'll be sure to post it. Thanks for your interest.

#15 Aer O'Head

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Posted 13 September 2010 - 12:25 AM

Do you have COPD as a result of smoking or because of a genetic disease? I have emphysema from the latter. I've also researched this problem quite a bit but it's the first time I learn about resveratrol helping. NAC has made a big different for me reducing shortness of breath significantly. There is also a body of research pointing to Vitamin A in the form of ATRA can actually regenerated the lung. Have you any info. on this ?

I thought about using nebulized Vitamin A for just this purpose. Can this be done ? I'm also curious about your regimen. I've seem to hit a wall in my research and maybe you can open new areas of interest for me.

There's plenty of information about resveratrol vis-a-vis emphysema. Use Google Scholar to search on resveratrol combined with any or several of the following: emphysema, copd, pulmonary, respiratory, lungs ... and then get carried away. As I mentioned in my original post, it all goes to oxidative stress, inflammation and the pathological responses thereto. I also mentioned that curcumin, NAC, and sulforaphane are basics in my regimen. I also nebulize reduced l-glutathione (GSH).

Yes, I've heard of the ATRA study (tretinoin, the acid form of Vitamin A that I've only seen in creams and gels) but I haven't seen much in its aftermath. Personally, I wouldn't be nuts about the idea of nebulizing Vitamin A, but if you do decide to go that route, be certain it's unadulterated! As for regeneration, you might also like to have a look at stem cells, hepatocyte growth factor and adrenomedullin. I wouldn't have the slightest idea as to where to obtain the latter two, at least at an affordable price, but I CAN refer you to a good stem cell doc. And no, he hasn't appeared on 60 Minutes, Dateline, or CNN, if you know what I mean! ;-)

P.S. After I walked away from the computer, I got to wondering if stem cell therapy would even work well for you. I assume that you're referring to alpha-1 antitrypsin deficiency when you state that you have the genetic form of emphysema. Which leads me to wonder if any regeneration would only be temporary in light of the underlying problem. Offhand, I simply don't know.

Edited by Aer O'Head, 13 September 2010 - 01:00 AM.


#16 Lufega

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Posted 13 September 2010 - 08:43 PM

I did more research on the ATRA study and concluded and vitamin A itself would work as well with chronic low/average doses. You guessed it right, I do have A1AT def. ( the MZ type). I am working hard to find a regimen that will increase AAT levels. I've come up with selenium and proline. I've posted the relevant research already. I'm confident that it's only a matter of time before I figure this out. At the same time, regenerating the lungs (which the research says is totally possible) at best, will level out the ongoing destruction. That is, I repair what's currently being destroyed to prevent any further long term damage.

One thing that is puzzling to me, however, is that all the supplements that are supposed to be helping me seem to be causing shortness of breat which is something I rarely experienced before. Either something is not working right (for instance, something in the Jarrow B-right gave me shortness of breath - I suspected niacin) or things are getting a bit worse before they get better.

I'm sorry you suffer from COPD but I'm happy to see someone else dedicating time and effort to researching this.

#17 Lufega

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Posted 13 September 2010 - 08:48 PM

Btw, thanks for leading me onto sulforaphane, I had missed that one (and resveratrol). I'm still a noob. I would be cautious with resveratrol. It is a potent copper chelator. Low copper status can further weaken your lungs and possibly exacerbate COPD. In fact, there is a type of emphysema caused solely by low copper status. I'll look it up later.

#18 maxwatt

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Posted 13 September 2010 - 09:08 PM

Btw, thanks for leading me onto sulforaphane, I had missed that one (and resveratrol). I'm still a noob. I would be cautious with resveratrol. It is a potent copper chelator. Low copper status can further weaken your lungs and possibly exacerbate COPD. In fact, there is a type of emphysema caused solely by low copper status. I'll look it up later.

The copper chelation effect is much exaggerated; concentrations of resveratrol that exhibited this in the lab are several orders of magnitude higher than can be obtained under physiological conditions.

Edited by maxwatt, 13 September 2010 - 09:08 PM.


#19 Lufega

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Posted 10 January 2011 - 01:54 AM

Bromelain reduces neutrophil migration in COPD. But I'm afraid that bromelain, being a protease itself, can damage elasin further. Any thoughts ??

Bromelain treatment decreases neutrophil migration to sites of inflammation.
Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP.

Department of Pathology, DUMC 3712, Duke University Medical Center, Durham, NC 27710, USA.


Abstract
Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50-85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.



#20 Young Paul

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Posted 07 February 2011 - 11:57 AM

what about dissolving in vodka then dilute with water, and then the nebulizer?

#21 maxwatt

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Posted 07 February 2011 - 12:01 PM

what about dissolving in vodka then dilute with water, and then the nebulizer?

I believe it would sting.

#22 Lufega

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Posted 26 February 2011 - 11:17 PM

I was a bit surprised by this. Lithium can improve lung healing by activation of the Wnt/beta-catenin signaling pathway. Awsome ! No idea what dose they used of if this could also work with low doses of lithium orotate.

Activation of the WNT/{beta}-Catenin Pathway Attenuates Experimental Emphysema.

Abstract
RATIONALE: Chronic obstructive pulmonary disease (COPD) is a devastating disease, for which no causal therapy is available.

OBJECTIVES: To characterize WNT/β-catenin signaling in COPD in humans and elucidate its potential role as a preventive and therapeutic target in experimental emphysema in mice.

METHODS: The expression, localization, and activity of WNT/β-catenin signaling was assessed in 12 COPD and 12 transplant donor samples using quantitative RT-PCR, immunohistochemistry, and Western blotting. The role of WNT/β-catenin signaling was assessed in elastase- and cigarette smoke-induced emphysema and therapeutic modulation thereof in elastase-induced emphysema in TOPGAL reporter and wild type mice in vivo.

MEASUREMENTS AND MAIN RESULTS: No differences in the mRNA expression profile of the main WNT/β-catenin signaling components were observed comparing COPD and donor lung homogenates. Immunohistochemical analysis revealed reduced numbers of nuclear !-catenin-positive alveolar epithelial cells in COPD. Similarly, WNT/β-catenin signaling was downregulated in both experimental emphysema models. Preventive, as well as therapeutic, WNT/β-catenin activation by lithium chloride attenuated experimental emphysema, as assessed by decreased airspace enlargement, improved lung function, reduced collagen content, and elevated expression of alveolar epithelial cell markers.

CONCLUSION: Decreased WNT/β-catenin signaling is involved in parenchymal tissue destruction and impaired repair capacity in emphysema. These data indicate a crucial role of WNT/β-catenin signaling in lung repair mechanisms in vivo, and highlight WNT/β-catenin activation as a future therapeutic approach for emphysema.

PMID: 20889911


Edited by Lufega, 26 February 2011 - 11:18 PM.


#23 niner

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Posted 27 February 2011 - 03:59 AM

what about dissolving in vodka then dilute with water, and then the nebulizer?

When the alcoholic resveratrol solution was diluted with water, the resveratrol would come out of solution as a fine suspension. Nebulizing this would result in insoluble fine particles being deposited in the lung, which I find pretty scary. I'm not confident that they would be absorbed; on the contrary I worry that a bad outcome might result. Without some evidence that this would work, I just wouldn't attempt it.

#24 rwac

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Posted 27 February 2011 - 04:25 AM

When the alcoholic resveratrol solution was diluted with water, the resveratrol would come out of solution as a fine suspension. Nebulizing this would result in insoluble fine particles being deposited in the lung, which I find pretty scary. I'm not confident that they would be absorbed; on the contrary I worry that a bad outcome might result. Without some evidence that this would work, I just wouldn't attempt it.


Hmm, I believe you can inhale alcohol straight from a nebulizer. I wonder if you need to be that scared, after all people inhale dust all the time and I'm sure the lungs have some self-cleaning mechanism.

#25 niner

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Posted 27 February 2011 - 04:34 AM

When the alcoholic resveratrol solution was diluted with water, the resveratrol would come out of solution as a fine suspension. Nebulizing this would result in insoluble fine particles being deposited in the lung, which I find pretty scary. I'm not confident that they would be absorbed; on the contrary I worry that a bad outcome might result. Without some evidence that this would work, I just wouldn't attempt it.


Hmm, I believe you can inhale alcohol straight from a nebulizer. I wonder if you need to be that scared, after all people inhale dust all the time and I'm sure the lungs have some self-cleaning mechanism.

The alcohol wouldn't be a problem (in reasonable quantities, and assuming it's diluted) but particulates are a huge problem. The lungs do have self cleaning mechanisms for the large particles that we are likely to encounter in nature. The sub-micron particulates that are produced by various modern industrial processes are a different story. They can get down into the alveoli where they are beyond the cilia that would sweep out large particles.

#26 Lufega

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Posted 27 February 2011 - 06:20 PM

Increasing expression of SOD-3 (copper/zinc) is very protective of the lung. Now, how to go about doing that ..... ?

Extracellular superoxide dismutase in the airways of transgenic mice reduces inflammation and attenuates lung toxicity following hyperoxia.
Folz RJ, Abushamaa AM, Suliman HB.

Department of Medicine, Duke University Medical Center, Durham, North Carolina, 27710, USA. rodney.folz@duke.edu


Abstract
Extracellular superoxide dismutase (EC-SOD, or SOD3) is the major extracellular antioxidant enzyme in the lung. To study the biologic role of EC-SOD in hyperoxic-induced pulmonary disease, we created transgenic (Tg) mice that specifically target overexpression of human EC-SOD (hEC-SOD) to alveolar type II and nonciliated bronchial epithelial cells. Mice heterozygous for the hEC-SOD transgene showed threefold higher EC-SOD levels in the lung compared with wild-type (Wt) littermate controls. A significant amount of hEC-SOD was present in the epithelial lining fluid layer. Both Tg and Wt mice were exposed to normobaric hyperoxia (>99% oxygen) for 48, 72, and 84 hours. Mice overexpressing hEC-SOD in the airways attenuated the hyperoxic lung injury response, showed decreased morphologic evidence of lung damage, had reduced numbers of recruited inflammatory cells, and had a reduced lung wet/dry ratio. To evaluate whether reduced numbers of neutrophil infiltration were directly responsible for the tolerance to oxygen toxicity observed in the Tg mice, we made Wt and Tg mice neutropenic using anti-neutrophil antibodies and subsequently exposed them to 72 hours of hyperoxia. Both Wt and Tg neutrophil-depleted (ND) mice have less severe lung injury compared with non-ND animals, thus providing direct evidence that neutrophils recruited to the lung during hyperoxia play a distinct role in the resultant acute lung injury. We conclude that oxidative and inflammatory processes in the extracellular lung compartment contribute to hyperoxic-induced lung damage and that overexpression of hEC-SOD mediates a protective response to hyperoxia, at least in part, by attenuating the neutrophil inflammatory response.



Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM.
Yao H, Arunachalam G, Hwang JW, Chung S, Sundar IK, Kinnula VL, Crapo JD, Rahman I.

Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, NY 14642, USA.


Abstract
Extracellular superoxide dismutase (ECSOD or SOD3) is highly expressed in lungs and functions as a scavenger of O(2)(*-). ECM fragmentation, which can be triggered by oxidative stress, participates in the pathogenesis of chronic obstructive pulmonary disease (COPD) through attracting inflammatory cells into the lungs. The level of SOD3 is significantly decreased in lungs of patients with COPD. However, the role of endogenous SOD3 in the development/progression of emphysema is unknown. We hypothesized that SOD3 protects against emphysema by attenuating oxidative fragmentation of ECM in mice. To test this hypothesis, SOD3-deficient, SOD3-transgenic, and WT C57BL/6J mice were exposed to cigarette smoke (CS) for 3 d (300 mg total particulate matter/m(3)) to 6 mo (100 mg/m(3) total particulate matter) or by intratracheal elastase injection. Airspace enlargement, lung inflammation, lung mechanical properties, and exercise tolerance were determined at different time points during CS exposure or after elastase administration. CS exposure and elastase administration caused airspace enlargement as well as impaired lung function and exercise capacity in SOD3-null mice, which were improved in mice overexpressing SOD3 and by pharmacological SOD mimetic. These phenomena were associated with SOD3-mediated protection against oxidative fragmentation of ECM, such as heparin sulfate and elastin, thereby attenuating lung inflammatory response. In conclusion, SOD3 attenuates emphysema and reduces oxidative fragmentation of ECM in mouse lung. Thus, pharmacological augmentation of SOD3 in the lung may have a therapeutic potential in the intervention of COPD/emphysema.


Does oral SOD/Glysodin make it inside the cell or does it stay in the extracellular area ? If so, it could act as an SOD3 mimetic.




Edited by Lufega, 27 February 2011 - 06:47 PM.


#27 Lufega

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Posted 27 February 2011 - 07:38 PM

Overexpression of Extracellular SOD/SOD3 also protects memory impairment in the brain.

#28 Lufega

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Posted 03 March 2011 - 04:04 AM

I was a bit surprised by this. Lithium can improve lung healing by activation of the Wnt/beta-catenin signaling pathway. Awsome ! No idea what dose they used of if this could also work with low doses of lithium orotate.

Activation of the WNT/{beta}-Catenin Pathway Attenuates Experimental Emphysema.

Abstract
RATIONALE: Chronic obstructive pulmonary disease (COPD) is a devastating disease, for which no causal therapy is available.

OBJECTIVES: To characterize WNT/β-catenin signaling in COPD in humans and elucidate its potential role as a preventive and therapeutic target in experimental emphysema in mice.

METHODS: The expression, localization, and activity of WNT/β-catenin signaling was assessed in 12 COPD and 12 transplant donor samples using quantitative RT-PCR, immunohistochemistry, and Western blotting. The role of WNT/β-catenin signaling was assessed in elastase- and cigarette smoke-induced emphysema and therapeutic modulation thereof in elastase-induced emphysema in TOPGAL reporter and wild type mice in vivo.

MEASUREMENTS AND MAIN RESULTS: No differences in the mRNA expression profile of the main WNT/β-catenin signaling components were observed comparing COPD and donor lung homogenates. Immunohistochemical analysis revealed reduced numbers of nuclear !-catenin-positive alveolar epithelial cells in COPD. Similarly, WNT/β-catenin signaling was downregulated in both experimental emphysema models. Preventive, as well as therapeutic, WNT/β-catenin activation by lithium chloride attenuated experimental emphysema, as assessed by decreased airspace enlargement, improved lung function, reduced collagen content, and elevated expression of alveolar epithelial cell markers.

CONCLUSION: Decreased WNT/β-catenin signaling is involved in parenchymal tissue destruction and impaired repair capacity in emphysema. These data indicate a crucial role of WNT/β-catenin signaling in lung repair mechanisms in vivo, and highlight WNT/β-catenin activation as a future therapeutic approach for emphysema.

PMID: 20889911


Resveratrol is not a good supplement to use if you have COPD. It will impede healing and lung parenchyma regeneration. The same goes for NAC, Curcumin, Quercetin and many other common nutraceuticals we use. What this study implies in treating COPD is monumental.

#29 Destiny's Equation

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Posted 16 March 2011 - 08:21 AM

Nebulizing supplements...you stole my idea! :P

Perhaps try choline or glutathione?

If you aren't sqeamish about particulate matter mullein in a cannabis-style vaporizer speeds lung healing.

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#30 Lufega

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Posted 16 March 2011 - 11:53 AM

Nebulizing supplements...you stole my idea! :P

Perhaps try choline or glutathione?

If you aren't sqeamish about particulate matter mullein in a cannabis-style vaporizer speeds lung healing.


I found mullein is awsome for breaking up mucus in the lung. It's much more effective than NAC. The mucus almost instantly dissolves. I would think that choline would have a broncho-constrictive effect ? Glutathione and maybe even SOD are possible candidates for inhaled therapy, if you could get them to dissolve into a solution.

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