Peroxynitrite, a Stealthy Biological Oxidant

Abstract

Peroxynitrite is the product of the diffusion-controlled reaction of nitric oxide and superoxide radicals. Peroxynitrite, a reactive short-lived peroxide with a pK a of 6.8, is a good oxidant and nucleophile. It also yields secondary free radical intermediates such as nitrogen dioxide and carbonate radicals. Much of nitric oxide-and superoxide-dependent cytotoxicity resides on peroxynitrite, which affects mitochondrial function and triggers cell death via oxidation and nitration reactions. Peroxynitrite is an endogenous toxicant but is also a cytotoxic effector against invading pathogens. The biological chemistry of peroxynitrite is modulated by endogenous antioxidant mechanisms and neutralized by synthetic compounds with peroxynitrite-scavenging capacity.

Pyruvate-Dependent Changes in Neutrophil Amino- and Alpha-Keto Acid Profiles or Immunity: Which Mechanisms Are Involved?

“…As studies impressively demonstrated: superoxide is able to kill bacteria directly, especially when the virulence of the pathogen is dramatically attenuated (i.e. by superoxide dismutase deficiency) [46] [47]. Here in this study, the inhibition of specific glutamine-dependent pathways were one important constituent in the significant turnaround of the pyruvate-induced alterations in the immune parameters examined.…”

Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases?

“…The term cytokine storm is used to accommodate the observation that multiple excessive inflammatory causes can induce excessive release of inflammation factors like interleukin-1, interleukin-6, interleukin-12, tumor necrosis factor-α, interferon-α, interferon-β, interferon-γ, Monocyte Chemoattractant Protein-1 and interleukin-8 thereby leading to a disease that appears similar to sepsis [30,31]. Importantly, excessive inflammation reactions can also induce acute oxidative stress [2]. Together, both cytokine storm and oxidative stress promote each other and induce MODS, result in high mortality rate [15].…”

“…In the past decade, molecular hydrogen was considered a surprising agent, which can significantly reduce oxidative stress by selectively reducing hydroxyl radical Hutaohong2010@163.com (•OH) and Peroxynitrite (ONOO-) [1,[8][9][10]. It has recently been revealed that hydrogen can both down-regulate expression of oxidative-related genes and pro-inflammatory cytokine genes directly and indirectly [2][3][4][5]11,12]. Oxidative stress and systemic inflammatory response syndrome have been confirmed to play critical roles in tissue and organ damages after polymicrobial sepsis injury, acute peritonitis injury, and peritonitis, which can develop into lethal sepsis with inappropriate treatment [13,14].…”

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AbstractHydrogen, a non-cytotoxic molecule, is one of nature's most simple elements [1,2]. Recent studies revealed that intraperitoneal injection of hydrogen-rich saline has surprising anti-inflammation, anti-oxidant, anti-apoptosis effects and protected organism against polymicrobial sepsis injury, acute peritonitis injury both by reducing oxidative stress and via decreasing mass proinflammatory responses.

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The neurotoxic effects of vitamin A and retinoids

“…They found that all-trans-retinoic acid induced nNOS expression through activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the orphan nuclear receptor DAX1 (NR0B1). All-trans-retinoic acid, among other retinoids, as for example, 9-cis-retinoic acid, are originated from vitamin A intake in vivo (Napoli 1996(Napoli , 1999(Napoli , 2012, and increased access to retinoids may lead to an increased expression of nNOS and augmented rates of NO production, which favors increased production of peroxynitrite (ONOO -), a reactive specie that give rise to nitryl cation (NO 2 + ), nitrogen diozide radical ( l NO 2 ), and hydroxyl radical ( l OH) through a reaction called homolytic fission (Radi 2013, Carballal et al 2014. In spite of this evidences, the effects of vitamin A supplementation on NOS enzyme activity and expression in the mammalian brain remain to be investigated.…”