In Vivo Spin Trapping of Nitric Oxide in Mice

Komarov, Andrei M.; Mattson, David L.; Jones, Mark M.; Singh, Pramod K.; Lai, Ching San

doi:10.1006/bbrc.1993.2170

Cited by 174 publications

(88 citation statements)

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“…Iron dithiocarbamate complexes such as DETC (12), MGD (14), proline dithiocarbamate (28), and N-(dithiocarboxy)sarcosine (29) have been used as spin-trapping agents for NO. Co-existence of these iron complexes and NO leads to an intense three-line EPR signal at room temperature.…”

Section: Discussionmentioning

confidence: 99%

“…The concentration of (MGD) 2 Fe 2ϩ complex in the blood of an animal during the quantitation of NO is initially estimated to be 0.01-5.71 mM (14,49,50,55,(61)(62)(63). As shown in Fig.…”

Section: No-forming Reaction From (Mgd)mentioning

confidence: 99%

“…Although the (DETC) 2 Fe 2ϩ complex has been widely used to trap NO from cells and tissues (12,13), quantitation of NO using (DETC) 2 Fe 2ϩ requires complicated procedures to overcome its low solubility in water. Recently, N-methyl-D-glucamine dithiocarbamate (MGD) has been used to overcome the poor solubility of (DETC) 2 Fe 2ϩ (14). The (MGD) 2 Fe 2ϩ complex ( Fig.…”

Section: ؉mentioning

confidence: 99%

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Nitric Oxide-forming Reaction between the Iron-N-Methyl-d-glucamine Dithiocarbamate Complex and Nitrite

Tsuchiya¹,

Yoshizumi²,

Hishida³

et al. 2000

Journal of Biological Chemistry

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The objective of this study was to elucidate the origin of the nitric oxide-forming reactions from nitrite in the presence of the iron-N-methyl-D-glucamine dithiocarbamate complex ((MGD) 2 Nitric oxide (NO) 1 has many important physiological roles which include that of a cytotoxic mediator of the immune system, regulation of vasomotor tone in the cardiovascular system, and as a neurotransmitter in the central nervous system (1, 2). NO is thought to be identical to the endothelium-derived relaxing factor (1), and its insufficiency is believed to contribute to the pathogenesis of vascular disease such as atherosclerosis, hypertension, and myocardial ischemia. As a result, much attention has been focused on the potential therapeutic ability of nitrovasodilators (e.g. nitroglycerin and nitroprusside) (3) and the anti-cancer drug hydroxyurea (4) to release NO.In order to understand the mechanisms by which NO, a diffusable free radical with a short lifetime, mediates various biological processes, accurate methods for its measurement are required. Several methods for the quantitation of NO such as chemiluminescence (1), methemoglobin formation (5), and electron paramagnetic resonance (EPR) spectroscopy of nitrosylmetal complexes (6) have been developed (7). Production of NO can also be indirectly assessed by measuring the nitric oxide oxidation product, nitrite, with the Griess reaction.EPR spectroscopy is the only specific general technique available for the detection and measurement of radical production, but has severe quantum mechanical limitations for diatomic molecules. EPR methods have been developed which stabilize NO as a polyatomic adduct using endogenous and exogenous spin traps (8 -14). Conventional nitrone-and nitroso-based spin traps are not capable of trapping NO as stable radical adducts, and nitromethane is an effective spin trap only at very alkaline pH values (15). The diethyldithiocarbamate (DETC) ferrous complex is a commonly used spin trap for NO (16), and the resultant (DETC) 2 Fe 2ϩ

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Section: Discussionmentioning

confidence: 99%

“…The concentration of (MGD) 2 Fe 2ϩ complex in the blood of an animal during the quantitation of NO is initially estimated to be 0.01-5.71 mM (14,49,50,55,(61)(62)(63). As shown in Fig.…”

Section: No-forming Reaction From (Mgd)mentioning

confidence: 99%

Section: ؉mentioning

confidence: 99%

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Nitric Oxide-forming Reaction between the Iron-N-Methyl-d-glucamine Dithiocarbamate Complex and Nitrite

Tsuchiya¹,

Yoshizumi²,

Hishida³

et al. 2000

Journal of Biological Chemistry

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“…7 Phototriggered NO generation from the ND micelles was first tested by electron spin resonance (ESR) spin-trapping using Nmethyl-D-glucamine dithiocarbamate complex ((MGD) 2 Fe 2+ ), which reacts with NO to give a stable paramagnetic complex, (MGD) 2 Fe 2+ NO. 10 Since the (MGD) 2 Fe 2+ NO complex gives a typical broadened three-line signal in the ESR spectrum, the generation of NO in the sample solution could be detected from the change in the spectrum. A freshly prepared (MGD) 2 Fe 2+ complex solution and ND micelles were mixed in a quartz cell (molar ratio:…”

Section: ¹1mentioning

confidence: 99%

PEGylated Polymer Micelle-based Nitric Oxide (NO) Photodonor with NO-mediated Antitumor Activity

Kanayama¹,

Yamaguchi²,

Nagasaki³

2010

Chemistry Letters

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PEGylated polymer micelles containing 4-nitro-3-trifluoromethylphenyl units within the core moiety were prepared, and their phototriggered nitric oxide (NO)-generating ability was confirmed by electron spin resonance (ESR) spin-trapping and the Griess method. These micelles were found to be capable of delivering exogenous NO into tumor cells in a photocontrolled manner and showed an NO-mediated antitumor effect, indicating the usability of this molecular system in NO-based tumor therapy.Nitric oxide (NO) is a free radical endogenously synthesized in the body and plays multiple physiological roles, including vasodilation, angiogenesis, neurotransmission, and immune response. Depending on its concentration and localization, NO has diverse biological functions.2 For example, NO can both promote and inhibit tumor progression depending on its local concentration. Relatively high concentrations of NO have been shown to inhibit tumor progression by promoting apoptosis.2 This means that a molecular system capable of site-specific delivery of a high amount of NO should be useful in antitumor treatment. Due to the poor bioavailability of NO, great efforts have been made to develop a methodology for the controlled delivery of exogenous NO in living systems.3 One promising approach is the exploitation of a photochemical process which can be spatiotemporally controlled by manipulating the incident light. Until now, various NO-photogenerative compounds (NO photodonors) have been developed and applied for the examination of photocontrolled NO delivery. 4,5 However, the development of NO photodonors with excellent water solubility, biocompatibility, and tumor specificity is still challenging. In this regard, we newly designed a PEGylated polymer micelle-based NO photodonor which contains NO photogenerative units in the core moiety. It is well recognized that PEGylated polymer micelles several tens of nanometers in size are potent carriers of various therapeutics agents.6 They show high colloidal stability under physiological conditions and preferentially accumulate in solid tumors by the enhanced permeation and retention (EPR) effect.7 Here, we wish to communicate the preparation of a PEGylated polymer micelle-based NO photodonor and its potential for NO-based therapeutic application.The PEG-based amphiphilic block copolymer used in this study [PEG-b-PNTP (PEG: 5000 g mol ¹1, PNTP: 3600 g mol ¹1 , DP PNTP (n) = 11] in Figure 1) was synthesized via conjugation between PEG-b-poly(4-chloromethylstyrene) 8 and 4-nitro-3-trifluoromethylphenol (NTP) in the presence of potassium carbonate. 9Nitrobenzene derivatives having bulky substituents at the orthoposition are known to generate NO upon appropriate light irradiation though a nitro-to-nitrite photorearrangement followed by the rupture of the ONO bond (Figure 1). 5 Micellization of PEGb-PNTP was carried out by dialysis. The hydrodynamic diameter and polydispersity index (PDI) of the resulting micelles (ND micelles) were determined by dynamic light scattering to be 42.3 nm and 0....

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“…These agents take advantage of the avid binding characteristics of metal complexes. Among the most characterized are NO complexes with iron [40][41][42], cobalt [43][44][45] and ruthenium [46,47] derivatives. At the time that other laboratories were evaluating the effect of broad-spectrum NOS inhibitors, early work in our laboratory took into consideration the principle that dithiocarbamate derivatives bind iron and this complex serves to bind NO.…”

Section: Evidence Using No Neutralizing Agentsmentioning

confidence: 99%

The complex role of iNOS in acutely rejecting cardiac transplants

Pieper

Roza

2008

Free Radical Biology and Medicine

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This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutelyrejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed.

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In Vivo Spin Trapping of Nitric Oxide in Mice

Cited by 174 publications

References 0 publications

Nitric Oxide-forming Reaction between the Iron-N-Methyl-d-glucamine Dithiocarbamate Complex and Nitrite

Nitric Oxide-forming Reaction between the Iron-N-Methyl-d-glucamine Dithiocarbamate Complex and Nitrite

PEGylated Polymer Micelle-based Nitric Oxide (NO) Photodonor with NO-mediated Antitumor Activity

The complex role of iNOS in acutely rejecting cardiac transplants

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