Nitric Oxide and Effect of a Radical Scavenger N-&lt;i&gt;tert&lt;/i&gt;-butyl-α-phenylnitrone on Stroke in a Rat Model

Saito, Kieko; Ikeda, Masahiko; Yoshioka, Hisashi; Tomita, Takako

doi:10.1159/000081223

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…Literature data suggest that PBN is able to reduce nitric oxide synthesis in vivo by blocking the nitric oxide synthase activity (23)(24)(25). Our results confirm the ability of PBN to reduce nitric oxide production, since in this experiment, PBN not only completely abolished the increase of nitrite concentration induced by the blank administration, but reduced even the nitritemia of the experimental animals.…”

Section: Discussionsupporting

confidence: 87%

Is nitrate a good biomarker of the nitric oxide status? / Este ionul nitrat un bun biomarker al producţiei endogene de monoxid de azot?

Croitoru¹,

Fülöp²,

Fogarasi³

et al. 2015

Romanian Review of Laboratory Medicine

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Section: Discussionsupporting

confidence: 87%

Is nitrate a good biomarker of the nitric oxide status? / Este ionul nitrat un bun biomarker al producţiei endogene de monoxid de azot?

Croitoru¹,

Fülöp²,

Fogarasi³

et al. 2015

Romanian Review of Laboratory Medicine

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“…In summary, all these effects by RNS and their derivatives described, i.e., binding of •NO to ETC irons, S-nitrosation, nitration and oxidation of respirasomal proteins, as well as peroxidation of lipids in the inner mitochondrial membrane, in particular, cardiolipin, can cause ETC dysfunction, since they block electron flux to a variable degree depending on the rates of •NO formation. Moderately elevated concentrations of •NO are not per se detrimental, but have, on the contrary, even been judged to be beneficial because of •OH scavenging, initiation of cGMP-mediated processes and stimulation of mitochondrial biogenesis [9,[60][61][62][63][64][65][66]. However, secondary bottlenecks or regional blockades of the ETC cause interruption of electron flux, eventually electron backflow and electron leakage [9,[14][15][16].…”

Section: Damage By Reactive Nitrogen Speciesmentioning

confidence: 99%

“…This would especially be the case under conditions of inflammation and in several neurodegenerative disorders. Although peroxynitrite and its products are responsible for a variety of diseases, basal or moderately enhanced •NO levels are obviously not detrimental, but rather beneficial [9,[60][61][62][63][64][65][66]111]. Therefore, the intention should never be to totally suppress •NO formation, nor should the physiological role of melatonin be sought in a complete downregulation of melatonin-sensitive NOS subforms.…”

Section: Regulation Of No Synthases By Melatonin and Amkmentioning

confidence: 99%

Melatonin and its metabolites as anti-nitrosating and anti-nitrating agents

Hardeland¹

2011

J Exp Integr Med

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Although basal and moderately elevated levels of nitric oxide are physiologically necessary and beneficial, excessive upregulations of this signaling molecule can be a cause of damage and cellular dysfunctions. In the presence of increased amounts of superoxide anions (•O2 -) and carbon dioxide, peroxynitrite (ONOO -) and the peroxynitrite-CO2 adduct (ONOOCO2 -) generate hydroxyl (•OH), nitrogen dioxide (•NO2) and carbonate (•CO3 -) radicals, which damage biomolecules by oxidation/peroxidation, nitration and nitrosation reactions. Nitrosation also occurs with all three NO congeners (NO + , •NO, and HNO = protonated NO -), with •NO especially in combination with electron/hydrogen-abstracting compounds, or with N2O3.3-Nitrotyrosine, found in low-density lipoprotein particles (LDL), atherosclerotic plaques, ion channels, receptors, transporters, enzymes and respirasomal subunits, is associated with numerous dysfunctions. Damage to the mitochondrial electron transport chain (ETC) is of particular significance and involves nitration, nitrosation and oxidation of proteins, cardiolipin peroxidation, and binding of •NO to ETC irons. Resulting bottlenecks of electron flux cause enhanced electron leakage which leads to elevated •O2 -. In combination with high •NO, •O2initiates a vicious cycle by generating more peroxynitrite that leads to further blockades and electron dissipation. Mitochondrial dysfunction, as induced via the •NO/peroxynitrite pathway, is of utmost importance in inflammatory diseases, especially sepsis, but also relevant to neurodegenerative and various other disorders. It may contribute to processes of aging.Melatonin, hormone of the pineal gland and product of other organs, interacts directly with reactive nitrogen species, but, more importantly, has antiinflammatory properties and downregulates inducible and neuronal NO synthases (iNOS, nNOS). It does not block moderately elevated •NO formation, but rather blunts excessive rises as occurring in sepsis and breaks the vicious cycle of mitochondrial electron leakage. The melatonin metabolite N 1 -acetyl-5-methoxykynuramine (AMK) forms stable nitrosation products and efficiently inhibits iNOS and nNOS, in conjunction with other antiinflammatory properties.

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“…Even beyond its obvious value in ischemia, beneficial effects have been described, which are also related to mitochondrial function. Scavenging of free radicals other than superoxide anions, such as hydroxyl radicals, were reported [ 173 , 174 ], but this may be judged critically because of simultaneous formation of peroxynitrite by interaction with the more abundant superoxide. However, NO was also shown to act, in PC12 cells, as an antiapoptotic agent, via activation of guanylate cyclase and the PI3 kinase/Akt pathway [ 175 ].…”

Section: Nitronesmentioning

confidence: 99%

Neuroprotection by Radical Avoidance: Search for Suitable Agents

Hardeland

2009

Molecules

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Neurodegeneration is frequently associated with damage by free radicals. However, increases in reactive oxygen and nitrogen species, which may ultimately lead to neuronal cell death, do not necessarily reflect its primary cause, but can be a consequence of otherwise induced cellular dysfunction. Detrimental processes which promote free radical formation are initiated, e.g., by disturbances in calcium homeostasis, mitochondrial malfunction, and an age-related decline in the circadian oscillator system. Free radicals generated at high rates under pathophysiological conditions are insufficiently detoxified by scavengers. Interventions at the primary causes of dysfunction, which avoid secondary rises in radical formation, may be more efficient. The aim of such approaches should be to prevent calcium overload, to reduce mitochondrial electron dissipation, to support electron transport capacity, and to avoid circadian perturbations. L-Theanine and several amphiphilic nitrones are capable of counteracting excitotoxicity and/or mitochondrial radical formation. Resveratrol seems to promote mitochondrial biogenesis. Mitochondrial effects of leptin include attenuation of electron leakage. Melatonin combines all the requirements mentioned, additionally regulates anti- and pro-oxidant enzymes and is, with few exceptions, very well tolerated. In this review, the perspectives, problems and limits of drugs are compared which may be suitable for reducing the formation of free radicals.

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Nitric Oxide and Effect of a Radical Scavenger N-<i>tert</i>-butyl-α-phenylnitrone on Stroke in a Rat Model

Cited by 6 publications

References 42 publications

Is nitrate a good biomarker of the nitric oxide status? / Este ionul nitrat un bun biomarker al producţiei endogene de monoxid de azot?

Is nitrate a good biomarker of the nitric oxide status? / Este ionul nitrat un bun biomarker al producţiei endogene de monoxid de azot?

Melatonin and its metabolites as anti-nitrosating and anti-nitrating agents

Neuroprotection by Radical Avoidance: Search for Suitable Agents

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