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looking for peroxynitrite (ONOO) scavengers ; how to obtain ebselen?


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#1 rotem

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Posted 12 February 2010 - 12:38 PM


ebselen (other name is harmokisane) is one of the peroxynitrite (ONOO) scavengers.
Do you know if it available commercially?

Also I'm looking for Nitric Oxide Synthase inhibitor (NOS inhibitor).
L-NAME [N(G)-nitro-L-arginine methyl ester] is one of them, but unfortunately doesn't available commercially.
Do you know of NOS inhibitor that is available commercially?

I want to take NOS inhibitor, because:
1. To decrease production of peroxynitrite and nitrative ( nitrosative ) stress and inflammation.

because: NO + superoxide -->peroxynitrite--> inflammation, DNA damage

L-Arginine Enhances Nitrative Stress And Exacerbates TNF-Alpha Toxicity To Human Endothelial Cells In Culture: prevention by propofol.

A Novel Mechanism, Uniquely Dependent on Mitochondrial Calcium Accumulation, Whereby Peroxynitrite Promotes Formation of Superoxide/Hydrogen Peroxide and the Ensuing Strand Scission of Genomic DNA.


2. NOS inhibition has anti-depressant properties:

stress -->increase NO--> increase nitrosylation of TPH2 (the enzyme that synthesize serotonin)-->less serotonin is synthesized-->depression, sleep problems
A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test.

The selective serotonin reuptake inhibitor fluoxetine reduces striatal in vivo levels of voltammetric nitric oxide (NO): A feature of its antidepressant activity?

http://www.ncbi.nlm....Pubmed_RVDocSum

http://www.ncbi.nlm....Pubmed_RVDocSum

eNOS gene deletion restores blood-brain barrier integrity and attenuates neurodegeneration in the thiamine-deficient mouse brain.

http://www.ncbi..nlm...t_uids=12668047

-------------
Also there is another kind of peroxynitrite scavenge- Porphyrins (metalloporphyrin) are peroxynitrite decomposition catalysts.
Do you know if one of them is available commercially?

http://www.ncbi.nlm.nih.gov/pubmed/18395709?ordinalpos=247&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

http://www.ncbi.nlm.nih.gov/pubmed/18684473?ordinalpos=106&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum


http://www.ncbi.nlm.nih.gov/pubmed/18591189?ordinalpos=148&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

iron porphyrin=FeTPPS

Edited by rotem, 12 February 2010 - 01:09 PM.

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#2 lynx

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Posted 12 February 2010 - 03:12 PM

PBN, nTBHA
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#3 tunt01

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Posted 12 February 2010 - 03:43 PM

i looked at this issue a bit. i came out drinking rosemary tea. look up rosemary.

#4 rwac

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Posted 12 February 2010 - 04:30 PM

Tocopherols and/or Tocotrienols may do the job.

Have you tried a full spectrum vitamin E ?

Edited by rwac, 12 February 2010 - 04:31 PM.


#5 pycnogenol

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Posted 12 February 2010 - 04:32 PM

Protection by Spices Against Cell Damage Caused by Peroxynitrite

Link:

http://www.life-enha...ate.asp?id=2024

"...many commonly used spices have potent protective properties against peroxynitrite.
A recent paper reports on the protective effects of cardamom, cinnamon, cloves, cumin,
nutmeg, paprika, rosemary, and turmeric..."


#6 VespeneGas

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Posted 12 February 2010 - 04:47 PM

I'd be really cautious reaching for a pharmacological NOS inhibitor. NO is a pretty important signaling molecule, and there would almost definitely be negative unintended consequences to indiscriminately inhibiting its synthesis. Just one that springs to mind:

NO targets SIRT1: a Novel Signaling Network in Endothelial Senescence

Rosemary and other spices are obviously safe in moderate doses, and probably beneficial.

#7 rotem

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Posted 13 February 2010 - 08:23 AM

link to my other queation - looking for ebselen or

#8 sentrysnipe

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Posted 13 February 2010 - 09:27 AM

Watch out for Rosemary contraindications: Hypertension.

#9 rotem

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Posted 13 February 2010 - 11:14 AM

more about why it is good to inhibit NOS. I'm not tlaking of completely inhibit it, but only decrease it.

The selective serotonin reuptake inhibitor fluoxetine reduces striatal in vivo levels of voltammetric nitric oxide (NO): A feature of its antidepressant activity?




also, link to my other queation - looking for ebselen or

#10 pone11

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Posted 26 February 2015 - 01:28 AM

I think the proposal to suppress nitric oxide would be a massive mistake.  Nitric oxide is how the body maintains the health of the endothelial lining, and it is the decline of nitric oxide levels as you age that starts a cascade that leads to inflammation inside the artery and sets you up for heart disease:

http://www.scielo.br...ipt=sci_arttext

 

In addition, I am not clear that the pathway that you describe is the only one to consider.   Tetrahydrobiopterin (BH4) is used in nitric oxide synthesis.  It takes two BH4 to create nitric oxide.  When BH4 goes short, the body creates Hydrogen Peroxide with one BH4.  And if no BH4 is available then the body creates superoxide.

http://www.jbc.org/c.../26736.full.pdf

 

In suppressing nitric oxide synthesis, you might be making other metabolites like BH4 available for increased synthesis of H2O2 and superoxide.

 

Nitric oxide is a critical signaling metabolite for the body, and I think you should not tinker with it without very very conclusive science and today what you have instead is a LOT of published research saying that nitric oxide is good for the endothelial lining and immune system, against some research that suggests it can have a negative effect.   

 

What you should do as a starting point is go buy some nitrite test strips from Berkeley Test:

http://www.berkeleyt...est-strips.html

 

If you are older you may just discover that you have the nitric oxide levels of a corpse, in which case your attempts to further suppress nitric oxide would be incredibly misguided and possibly dangerous.


Edited by pone11, 26 February 2015 - 01:31 AM.


#11 Darryl

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Posted 26 February 2015 - 06:56 AM

Folate.

 

Rezk, B. M., Haenen, G. R., van der Vijgh, W. J., & Bast, A. (2003). Tetrahydrofolate and 5-methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophoreFEBS letters555(3), 601-605.


The presumed protective effect of folic acid on the pathogenesis of cardiovascular, hematological and neurological diseases and cancer has been associated with the antioxidant activity of folic acid. Peroxynitrite (PON) scavenging activity and inhibition of lipid peroxidation (LPO) of the physiological forms of folate and of structurally related compounds were tested. It was found that the fully reduced forms of folate, i.e. tetrahydrofolate (THF) and 5-methyltetrahydrofolate (5-MTHF), had the most prominent antioxidant activity. It appeared that their protection against LPO is less pronounced than their PON scavenging activity. The antioxidant activity of these forms of folic acid resides in the pterin core, the antioxidant pharmacophore is 4-hydroxy-2,5,6-triaminopyrimidine. It is suggested that an electron donating effect of the 5-amino group is of major importance for the antioxidant activity of 4-hydroxy-2,5,6-triaminopyrimidine. A similar electron donating effect is probably important for the antioxidant activity of THF and 5-MTHF.
 
See also

 

Gori, T., Burstein, J. M., Ahmed, S., Miner, S. E., Al-Hesayen, A., Kelly, S., & Parker, J. D. (2001). Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance a human in vivo studyCirculation,104(10), 1119-1123. Van Etten, R., de Koning, E., Verhaar, M., Gaillard, C. A. J. M., & Rabelink, T. (2002). Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folateDiabetologia45(7), 1004-1010.

Shirodaria, C., Antoniades, C., Lee, J., Jackson, C. E., Robson, M. D., Francis, J. M., ... & Channon, K. M. (2007). Global Improvement of Vascular Function and Redox State With Low-Dose Folic Acid Implications for Folate Therapy in Patients With Coronary Artery DiseaseCirculation115(17), 2262-2270.

McCarty, M. F., Barroso-Aranda, J., & Contreras, F. (2009). High-dose folate and dietary purines promote scavenging of peroxynitrite-derived radicals–Clinical potential in inflammatory disordersMedical hypotheses73(5), 824-834..

Antoniades, C., Shirodaria, C., Leeson, P., Baarholm, O. A., Van-Assche, T., Cunnington, C., ... & Channon, K. M. (2009). MTHFR 677 C> T Polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosisCirculation119(18), 2507-2515.

Stanger, O., & Wonisch, W. (2012). Enzymatic and non-enzymatic antioxidative effects of folic acid and its reduced derivates. In Water Soluble Vitamins (pp. 131-161). Springer Netherlands.

 



#12 timar

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Posted 26 February 2015 - 09:39 AM

The amount of folate in the bloodstream is minuscle, though, and its antioxidant activity negligible compared to endogenous antioxidants.

 

(That should not stop you from eating your leafy greens, as folate is critical for the synthesis of DNA repair enzymes)

 

Anyway, I have to agree with pone11 - you really don't want to supress nitric oxide production!


Edited by timar, 26 February 2015 - 09:42 AM.


#13 Hepoberman

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Posted 28 February 2015 - 02:04 PM

Gamma Tocopherols.

 

"Despite alpha tocopherol’s superior antioxidant abilities, gamma tocopherol is required to remove peroxynitrite and other nitrogen- containing toxins that are responsible for initiating the inflammatory response. Acting through a mechanism unavailable to alpha tocopherol, gamma tocopherol reacts with and removes these harmful reactive nitrogen oxides, thereby helping to subdue the inflammatory cascade."

 

What Makes Gamma Tocopherol Superior to Alpha Tocopherol By Lyle MacWilliam, MSc, FP  

 


Edited by Hepoberman, 28 February 2015 - 02:04 PM.


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#14 timar

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Posted 28 February 2015 - 06:09 PM

 

What a ridiculous title - the usual LEF puffery. "What makes pears superior to apples"... well, they are two similar things with some similar but also very different properties and none is superior to the other. But of course, alpha-tocopherol is dirt-cheap, so you have to come up with a good story in order to convince people to buy the much more expensive mixed tocopherol supplement.

 

I'm all for getting a good mix of tocols, but I'm annoyed by all this pseudo-scientific puffery based on some animal or petri dish studies. If we look at dietary patterns, wo know that one of healthiest ever studied, the traditional Mediterranean diet, is rich in alpha-tocopherol (from olive oil and nuts) and relatively poor in gamma-tocopherol, whereas the SAD with all its fried food and processed convenience food is poor in alpha-tocopherol and extremely rich in gamma-tocopherol (from sunflower, soy and corn oils). Now lets see wich diet causes inflammation...
 


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