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Review ArticleOpen Access

The Underrated Carbonate Radical (CO3) – Detoxification and Reduced Formation by Melatonin

Rüdiger Hardeland*

DOI: 10.26717/BJSTR.2017.01.000264

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    • University of Goettingen, Germany
    • Corresponding author: Rüdiger Hardeland, Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Goettingen, Buergerstr. 50, D-37073 Göttingen, Germany

Received: July 27, 2017;   Published: August 09, 2017

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Carbonate radicals are frequently overlooked or underrated oxidants that have a considerably larger range of action than the short-lived hydroxyl radicals. They possess sufficient reactivity for abstracting electrons or hydrogen atoms from many biomolecules. Carbonate radicals are formed in several reactions, e.g., via hydrogen abstraction from bicarbonate by a hydroxyl radical, through interaction of a formate radical with bicarbonate and, most importantly, from the peroxynitrite-carbon dioxide adduct. All these pathways of formation indicate an important role of carbon dioxide and bicarbonate levels for the generation of carbonate radicals and, therefore, many oxidizing reactions with aromates can be considerably enhanced by adding bicarbonate. Under physiological and, even more, pathophysiological conditions, high CO2/HCO3 concentrations are found in mitochondria and in situations of under-perfusion or ischemia. Increased levels of nitric oxide considerably increase via generation of peroxynitrite the formation of carbonate radicals, effects of relevance with regard to inflammation, Alzheimer’s disease, stroke, and all pathologies related to mitochondrial dysfunction. Melatonin counteracts both the formation and persistence of carbonate radicals, by down regulating inducible and neuronal NO synthases, by scavenging carbonate radicals, and by protecting mitochondria. By interaction with carbonate radicals, melatonin is converted to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), another protective compound, which is metabolized to N1-acetyl-5-methoxykynuramine (AMK). AMK also down regulates inducible and neuronal NO synthases and scavenges carbonate radicals as well as various reactive oxygen species.

|Abstract| |Introduction| |Damage by Free Radicals in Relation to CO2 Abundance| |Multiple Levels of Protection by Melatonin Against Damage by CO3| |Conclusion| |References|