scholarly journals Peroxynitrite: mediator of the toxic action of nitric oxide.

1996 ◽  
Vol 43 (4) ◽  
pp. 645-659 ◽  
Author(s):  
G Bartosz

Peroxynitrite (oxoperoxonitrate(-1)), anion of peroxynitrous acid, is thought to mediate the toxic action of nitric oxide and superoxide anion. Peroxynitrite is formed in a fast reaction between these species, reacts with all classes of biomolecules, is cytotoxic, and is thought to be involved in many pathological phenomena. Its main reactions involve one- and two-electron oxidation and nitration. Protein nitration is often used as a footprint of peroxynitrite reactions in vivo. Nitration of tyrosine and of tyrosyl residues in proteins may be an important mechanism of derangement of biochemical signal transduction by this compound. However, apparently beneficial effects of peroxynitrite have also been described, among them formation of nitric oxide and nitric oxide donors in reactions of peroxynitrite with thiols and alcohols.

2002 ◽  
Vol 161 (4) ◽  
pp. 1409-1418 ◽  
Author(s):  
Maria Laura Giustizieri ◽  
Cristina Albanesi ◽  
Claudia Scarponi ◽  
Ornella De Pità ◽  
Giampiero Girolomoni

2004 ◽  
Vol 286 (2) ◽  
pp. H768-H774 ◽  
Author(s):  
Chu Kataoka ◽  
Kensuke Egashira ◽  
Minako Ishibashi ◽  
Shujiro Inoue ◽  
Weihua Ni ◽  
...  

Amlodipine (a new class of calcium channel antagonist) has been shown to limit the progression of arteriosclerosis and decrease the incidence of cardiovascular events. The mechanisms underlying the beneficial effects of amlodipine, however, remain unclear. Therefore, we hypothesized that amlodipine attenuates the development of arteriosclerosis through the inhibition of inflammation in vivo. Long-term inhibition of nitric oxide (NO) by administration of a NO synthase inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), to rats induces coronary vascular inflammation [monocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, increased activity of angiotensin-converting enzyme (ACE)], and arteriosclerosis. Here, we used the rat model to investigate the anti-inflammatory effects of amlodipine in vivo. Treatment with amlodipine markedly inhibited the l-NAME-induced increase in vascular inflammation, oxidative stress, and local ACE and Rho activity and prevented arteriosclerosis. Interestingly, amlodipine prevented the l-NAME-induced increase in MCP-1 receptor CCR2 expression in circulating monocytes. Amlodipine markedly attenuated the high mortality rate at 8 wk of treatment. These data suggest that amlodipine attenuated arteriosclerosis through inhibiting inflammatory disorders in the rat model of long-term inhibition of NO synthesis. The anti-inflammatory effects of amlodipine seem to be mediated not only by the inhibition of local factors such as MCP-1 but also by the decrease in CCR2 in circulating monocytes. Inhibition of the MCP-1 to CCR2 pathway may represent novel anti-inflammatory actions of amlodipine beyond blood pressure lowering.


2009 ◽  
Vol 25 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Samantha Carreiro ◽  
Scott Anderson ◽  
Hovhannes J. Gukasyan ◽  
Achim Krauss ◽  
Ganesh Prasanna

Author(s):  
Tianxiang Ma ◽  
Zhexi Zhang ◽  
Yu Chen ◽  
Haoran Su ◽  
Xiaoyan Deng ◽  
...  

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of Coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in cardiovascular system, the clinical applications centered on the NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process based on the clinical images and mathematical modeling to assess the endothelial function and vulnerability of atherosclerotic plaque. Then, the emerging bioimaging technologies that have the potential to directly measure the arterial NO concentration were discussed, including the Raman spectroscopy and electrochemical sensor. Aside from the diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the inhaled NO therapy to treat the pulmonary hypertension and COVID-19, stem cell therapy and NO-releasing platform to treat endothelial dysfunction and atherosclerosis.


2016 ◽  
Vol 43 (9) ◽  
pp. 870 ◽  
Author(s):  
Santiago Signorelli ◽  
Camila Imparatta ◽  
Marta Rodríguez-Ruiz ◽  
Omar Borsani ◽  
Francisco J. Corpas ◽  
...  

Plants accumulate proline under diverse types of stresses, and it has been suggested that this α-amino acid has the capacity to protect against oxidative stress. However, it is still controversial whether its protection is due to the direct scavenging of reactive oxygen species (ROS). To solve this issue and considering that nitrosative stress is directly related with an oxidative stress condition, we evaluated whether proline can protect against nitrosative damage. Using proteins of Lotus japonicus (Regel) K.Larsen leaves exposed to a peroxynitrite (ONOO–/ONOOH) generator in presence and absence of 100mM proline, the potential of proline to protect was analysed by the protein nitration profile and NADP-dependent isocitrate dehydrogenase activity, which is inhibited by nitration. In both cases, the presence of proline did not diminish the peroxynitrite effects. Additionally, proline biosynthesis Arabidopsis knockout (KO) mutant plants of Δ(1)-pyrroline-5-carboxylate synthetase1 (P5CS1) gene, designated as Atp5cs1-1 and Atp5cs1-4, showed similar protein nitration levels as wild-type plants under salinity-induced oxidative stress, despite mutants having higher levels of lipid oxidation, H2O2 and superoxide (O2·–). Finally, by a fluorometric assay using specific fluorescent probes, it was determined that the presence of 100mM proline did not affect the time-course content of peroxynitrite or nitric oxide generation in vitro. Our results reveal the relevance of proline accumulation in vivo under stress, but unequivocally demonstrate that proline is not a direct scavenger of peroxynitrite, superoxide, ·NO and nitrogen dioxide (·NO2).


2011 ◽  
Vol 36 (2) ◽  
pp. 07-20 ◽  
Author(s):  
José Carlos Rebuglio Vellosa ◽  
Luis O. Regasini ◽  
Najeh Maissar Khalil ◽  
Vanderlan da Silva Bolzani ◽  
Omar A. K. Khalil ◽  
...  

The aim of the present study was to investigate a cytotoxic oxidative cell stress related and the antioxidant profile of kaempferol, quercetin, and isoquercitrin. The flavonol compounds were able to act as scavengers of superoxide anion (but not hydrogen peroxide), hypochlorous acid, chloramine and nitric oxide. Although flavonoids are widely described as antioxidants and this activity is generally related to beneficial effects on human health, here we show important cytotoxic actions of three well known flavonoids. They were able to promote hemolysis which one was exacerbated on the presence of hypochlorous acid but not by AAPH radical. Therefore, despite they expected scavenger action over free radicals an oxidants, these compounds could be very lesive to living organisms by acting over erythrocytes and maybe other cellular types.


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