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- Peroxynitrites -


General Information:

Names:
Wikipedia entry:
Dr. Ray Shahelien entry: 

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Observations:

It turns out that the same toxin (peroxynitrite) that probably causes damage to the brain in Alzheimer's disease also damages the brain as a result of a stroke.

http://www.jneurosci.org/content/19/14/5910.short
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865248/

Various essential oils protect the brain in four ways: they limit the formation of peroxynitrites, they lower levels of peroxynitrites, they inhibit peroxynitrite-mediated damage, and they partially reverse the damage done by peroxynitrites.  In essence, they limit the damage done to the brain by stroke and Alzheimer's disease.
See also"aromatherapy in the treatment of Alzheimer's disease" http://www.alzconnected.org/discussion.aspx?g=posts&t=2147484055

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Known sources:


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Natural sources:


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References:

Richardson:
Free radicals in the genesis of Alzheimer's disease
J. S. Richardson
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
 
"As part of an ongoing investigation of the role of oxygen free radicals in Alzheimer's disease (AD), the formation of peroxidation products, the activities of free radical defense enzymes, and the level of total iron were determined in autopsy brain tissue from donors with AD and from age-matched non-demented donors."
[Is this the "Dr. Richardson" cited by http://www.consumerhealth.org/articles/display.cfm?ID=19990303140150 ?  If so, they got his title wrong!]
[Seems as though chelation therapy with EDTA depletes excess iron as well as other metals.  Perhaps this is the reason why chelation therapists have noticed an improvement in their patients who suffer from AD.  Aluminum might be, as someone put it, "an innocent bystander".]
http://www.annalsnyas.org/cgi/content/abstract/695/1/73
 
[An interesting Google search on on-line articles referencing the above.  Hopefully the link works.]
http://scholar.google.com/scholar?q=link:http%3A%2F%2Fwww.annalsnyas.org%2Fcgi%2Fcontent%2Fabstract%2F695%2F1%2F73
 
[Other papers by Richardson]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=PubMed&term=Richardson+%22University+of+Saskatchewan%22+Alzheimer%27s&tool=QuerySuggestion
"Cerebral microischemia as a potential precipitant of the neurodegenerative cascade of Alzheimer's disease."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9329719&dopt=Abstract


Neuroprotection by minocycline caused by direct and specific scavenging of peroxynitrite.
Schildknecht S, Pape R, Müller N, Robotta M, Marquardt A, Bürkle A, Drescher M, Leist M.
J Biol Chem. 2011 Feb 18;286(7):4991-5002. Epub 2010 Nov 16.
Source: Department of In Vitro Toxicology and Biomedicine, Faculty of Biology, University of Konstanz, 78457 Konstanz, Germany.
Abstract
Minocycline prevents oxidative protein modifications and damage in disease models associated with inflammatory glial activation and oxidative stress. Although the drug has been assumed to act by preventing the up-regulation of proinflammatory enzymes, we probed here its direct chemical interaction with reactive oxygen species. The antibiotic did not react with superoxide or (•)NO radicals, but peroxynitrite (PON) was scavenged in the range of ∼1 μm minocycline and below. The interaction of pharmacologically relevant minocycline concentrations with PON was corroborated in several assay systems and significantly exceeded the efficacy of other antibiotics. Minocycline was degraded during the reaction with PON, and the resultant products lacked antioxidant properties. The antioxidant activity of minocycline extended to cellular systems, because it prevented neuronal mitochondrial DNA damage and glutathione depletion. Maintenance of neuronal viability under PON stress was shown to be solely dependent on direct chemical scavenging by minocycline. We chose α-synuclein (ASYN), known from Parkinsonian pathology as a biologically relevant target in chemical and cellular nitration reactions. Submicromolar concentrations of minocycline prevented tyrosine nitration of ASYN by PON. Mass spectrometric analysis revealed that minocycline impeded nitrations more effectively than methionine oxidations and dimerizations of ASYN, which are secondary reactions under PON stress. Thus, PON scavenging at low concentrations is a novel feature of minocycline and may help to explain its pharmacological activity.
PMID: 21081502 [PubMed] PMCID: PMC3037611
http://www.ncbi.nlm.nih.gov/pubmed/21081502
Full Text:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037611/


Prevention of peroxynitrite-dependent tyrosine nitration and inactivation of alpha1-antiproteinase by antibiotics.
Whiteman M, Halliwell B.
Free Radic Res. 1997 Jan;26(1):49-56.
Source: Neurodegenerative Disease Research Centre, King's College London, UK.
Abstract

Peroxynitrite, formed by reaction of superoxide and nitric oxide, appears to be an important tissue damaging species generated at sites of inflammation. In this paper, we compare the abilities of several antibiotics to protect against peroxynitrite-dependent inactivation of alpha1-antiproteinase, and to inhibit tyrosine nitration by peroxynitrite, in vitro. Tetracycline, minocycline, doxycycline, rifamycin and rifampicin were highly protective in both assay systems, whereas several other antibiotics tested were not. The possibility that antibiotics could affect tissue injury at sites of inflammation by scavenging peroxynitrite is discussed.
PMID: 9018471 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/9018471

http://ukpmc.ac.uk/abstract/MED/9018471


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Updated: July 2, 2012
Inception: July 2, 2012