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Super Oxide 101 - Another Reason To Get Out of Fight or Flight (Produces Super Oxide)

This article is not medical or healthcare advice. Before starting any health related regimen please seek the advice of your Primary Care Physician or an M.D.


This article is all about Super Oxide, perhaps the most significant free radical, causing oxidative stress, and is associated with a long list of health issues : Alzheimers, Parksinson's, ME / CFS, Autism, diabetes, endothelial dysfunction, cardio vascular disease, and many others. This series of articles will be followed by articles on how to support the by product of neutralizing Super Oxide, Hydrogen Peroxide. Supporting the body's systems to neutralize Hydrogen Peroxide (a radical itself) before embarking on Super Oxide reduction strategies should be considered.


Irwin Fridovich, a biochemist, first proposed the Super Oxide Theory in 1969 - that super oxide is the origin of most reactive oxygen species, and a major factor in various diseases like Parkinsons, Alzheimers, Cardio vascular disease, and many others. He was the person who first found the SOD genes (Super Oxide Dismutase). He has published more than 500 academic papers, that have been cited more than 50,000 times. He also discovered that excess super oxide inactivates several kreb's cycle enzymes, as well as Fumarases A and B. He was a Professor James B. Duke Emeritus of Medicine 1919-1929.


This article (SU 101) and following series on Super Oxide, will be organized into 4 main parts. Part 1 - this article will provide a general overview, Part 2 of Super Oxide, SU 102, will focus on the body's systems that process and neutralize super oxide, and SU 103 will focus on we can calm down the production of super oxide, and SU 104 will focus on how to support (think necessary cofactors) and up regulate (herbs and compounds that stimulate the body's genes to process super oxide) the body's natural systems to neutralize super oxide. Before i go into details with these various follow on parts - this article will provide an overview.


Super oxide is produced primarily from the following list of the body's systems and issues by two main processes - enzymatic reactions and by hazard events (detox of benzene, radiation, etc):

  1. NOS Uncoupling (NOS2 / NOS3) - found to precede 86% of all cardiac arrests

  2. Mitochondrial Electron Transport Chain (Mainly Complex 1, III, with the primary substrate Succinate) - thought to produce 80% of all super oxide

  3. NADPH (NOX Genes) - in particular NOX2 that produces oxidative bursts of SO to kill pathogens, and NOX4 which is found over active before cardiac arrests often.

    1. NADPH Oxidase can be activated by elevated by Angiotensin and Aldosterone [5]

  4. Glutathione Recycling (GSR Gene)

  5. Intracellular Calcium Dysregulation - from things like EMF exposure, etc

  6. Ferroptosis - a key process found in mold exposure, Long Haul, and cancer. Can be initiated by high doses of Selenium. Doses 200 mcg / day and higher are suspected to initiate ferroptosis and the production of Super Oxide, Inhibits the antiporter SLC7A11 - that imports Cysteine into the glutathione system, Increases DMT and Iron uptake, shuts down GSH (Glutathione), and shuts down GPX4.

  7. Processing compounds such as : Adrenalin, Dopamine, Norepenephrine, Serotonin and hormones like estrogen

  8. Detoxification of various xenobiotics like benzene, etc

  9. Mast Cell Degranulation

  10. High homocysteine [8]

  11. Hemoglobin degradation and oxidation [11]

The body's systems to neutralize Super Oxide Include:

  1. Super Oxide Dismutase (SOD1 - Cu, Zn, SOD2 - Manganese, SOD3 - Cu)

  2. F12 - a gene that is directly correlated to SOD2 concentrations inside the mitochondria

  3. PON1 - yes the same gene that processes glyphosate and other xenobiotics, like Saran gas in GWS. Its the back up system to help neutralize Super Oxide.

  4. NQO1 - Yep! The same gene that converts ubiquinol to ubiquinone, recycles NAD, detoxes benzene, also cleans up super oxide from quinones produces in various processes.

    1. A list of substances that NQO1 breaks down producing super oxide include: Rosemary, Milk Thistle, Quercetin, Luteolin, Genistein, Resveratrol, tea, caeffeic acid, tryptamine, ECGC, Black Cummin Seed, BPA breakdown products, PCB breakdown products, and more!!!!

  5. Super Oxide Scavenging compounds:

    1. B12 - this is really about scavenging Super Oxide. Hydroxy b12 is an excellent pyroxynitrite scavenger.

    2. Other super oxide scavengers include : Rutin, Quercetin, Naringin, and Garlic, Schima wallichii. [1, 2]

    3. Other studies on Super Oxide Scavengers find the following in rank order of effectiveness: dihydromyricetin, myricetin, quercetin, kaempferol, , baicalein.[3]

    4. Another study evaluated other compounds and found them effective in the following order:  Ginkgo biloba extract, pycnogenol, ~3-catechin, tea and BioNormalizer. [4]



References:

  1. Superoxide scavenging by polyphenols: effect of conjugation and dimerization A. Cano, M.B. Arnao, G. Williamson & M-T. Garcia-Conesa . Redox Report Communications in Free Radical Research ISSN: 1351-0002. (2002) Redox Report, 7:6, 379-383, DOI: 10.1179/135100002125001153.

  2. Evaluation of the free-radical scavenging and antioxidant activities of Chilauni, Schima wallichii Korth in vitro. K Lalhminghlui ‡ , 1 and Ganesh Chandra JagetiaFuture Sci OA. 2018 Feb; 4(2): FSO272. Published online 2018 Jan 4. doi: 10.4155/fsoa-2017-0086 PMCID: PMC5778377. PMID: 29379645

  3. An Improved System to Evaluate Superoxide-Scavenging Effects of Bioflavonoids Prof. Yuanyong Yao, Prof. Shixue Chen, Dr. Hu Li. Chemistry Open. First published: 28 April 2021. https://doi.org/10.1002/open.202100013

  4. HYDROXYL AND SUPEROXIDE ANION RADICAL SCAVENGING ACTIVITIES OF NATURAL SOURCE ANTIOXIDANTS USING THE COMPUTERIZED JES-FR30 ESR SPECTROMETER SYSTEM Yasuko Noda*, Kazunori Anza. Vol. 42, No. 1, June 1997 BIOCHEMISTRY and MOLECULAR BIOLOGY INTERNATIONAL Pages 35-44

  5. Superoxide anion and hydrogen peroxide-induced signaling and damage in angiotensin II and aldosterone action. Nina Queisser 1Gholamreza FazeliNicole Schupp. Biol Chemistry.  2010 Nov;391(11):1265-79. doi: 10.1515/BC.2010.136. PMID: 20868230. DOI: 10.1515/BC.2010.136

  6. Role of oxidative stress in neurodegenerative disorders: a review of reactive oxygen species and prevention by antioxidants Annwyne Houldsworth. https://doi.org/10.1093/braincomms/fcad356 BRAIN COMMUNICATIONS 2024

  7. The Effect of Homocysteine on the Secretion of Il-1β, Il-6, Il-10, Il-12 and RANTES by Peripheral Blood Mononuclear Cells—An In Vitro Study Magdalena Borowska,1,* Hanna Winiarska. Molecules. 2021 Nov; 26(21): 6671. Published online 2021 Nov 4. doi: 10.3390/molecules26216671.PMCID: PMC8588228. PMID: 34771080

  8. Hyperhomocysteinemia, Oxidative Stress, and Cerebral Vascular Dysfunction. By Frank M. Faraci and Steven R. Lentz. 1 Feb 2004 in Stroke Vol 35. Number 2. https://doi.org/10.1161/01.STR.0000115161.10646.67Stroke. 2004;35:345–347.

  9. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. By Hoi-Shan Wong,1 Pratiksha A. Dighe, Vojtech MezerJ Biol Chem. 2017 Oct 13; 292(41): 16804–16809. Published online 2017 Aug 24. doi: 10.1074/jbc.R117.789271. PMCID: PMC5641882. PMID: 28842493

  10. A mitochondrial superoxide theory for oxidative stress diseases and aging. By Hiroko P. Indo,1,2,3 Hsiu-Chuan Yen,. J Clin Biochem Nutr. 2015 Jan; 56(1): 1–7. Published online 2014 Dec 23. doi: 10.3164/jcbn.14-42. PMCID: PMC4306659. PMID: 25834301

  11. Superoxide Dismutase: Therapeutic Targets in SOD Related Pathology. Filip Cristiana, Albu Elena, Zamosteanu Nina. Vol.6 No.10, April 2014. DOI: 10.4236/health.2014.610123

  12. Reactive Oxygen Species and Their Involvement in Red Blood Cell Damage in Chronic Kidney Disease. Krzysztof Gwozdzinski, Anna Pieniazek, and Lukasz Gwozdzinski. Oxid Med Cell Longev. 2021; 2021: 6639199. Published online 2021 Feb 25. doi: 10.1155/2021/6639199. PMCID: PMC7932781. PMID: 33708334

  13. Role of peroxiredoxin-2 in protecting RBCs from hydrogen peroxide-induced oxidative stress E. Nagababu,1 J. G. Mohanty,. Free Radic Res. Author manuscript; available in PMC 2018 Apr 23. Free Radic Res. 2013 Mar; 47(3): 164–171. Published online 2013 Jan 9. doi: 10.3109/10715762.2012.756138. PMCID: PMC5911927. NIHMSID: NIHMS949983 PMID: 23215741

  14. ReviewImplications and progression of peroxiredoxin 2 (PRDX2) in various human diseases. By Priyanka Balasubramanian a, Varshini Vijayarangam. Volume 254, February 2024, 155080. https://doi.org/10.1016/j.prp.2023.155080

  15. The critical role of peroxiredoxin-2 in colon cancer stem cells Linglong Peng,1,* Yongfu Xiong. Aging (Albany NY). 2021 Apr 30; 13(8): 11170–11187. Published online 2021 Mar 26. doi: 10.18632/aging.202784. PMCID: PMC8109100 PMID: 33819194

  16. Deficiency of peroxiredoxin 2 exacerbates angiotensin II-induced abdominal aortic aneurysm. By Se-Jin Jeong, Min Ji Cho, et. al. Experimental & Molecular Medicine volume 52, pages1587–1601 (2020)

  17. Peroxiredoxin 2 is associated with colorectal cancer progression and poor survival of patients. Oncotarget. 2017; 8:15057-15070. https://doi.org/10.18632/oncotarget.14801. By   LingLong Peng1,*, Rong Wang1,*, JingKun Shang.

  18. Roles of peroxiredoxins in cancer, neurodegenerative diseases and inflammatory diseases Mi Hee Park,a MiRan Jo. Pharmacol Ther. 2016 Jul; 163: 1–23. Published online 2016 Apr 26. doi: 10.1016/j.pharmthera.2016.03.018. PMCID: PMC7112520. PMID: 27130805

  19. Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Sonia Salzano,a,1 Paola Checconi,.  Proc Natl Acad Sci U S A. 2014 Aug 19; 111(33): 12157–12162. Published online 2014 Aug 5. doi: 10.1073/pnas.1401712111. PMCID: PMC4143057. PMID: 25097261

  20. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Tarique Hussain,1,2Bie Tan. Volume 2016 | Article ID 7432797 https://doi.org/10.1155/2016/7432797.

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