Appearance of Electron Spin Resonance Signals in the Interaction of Dithiocarbamate-Fe(II) with Nitrogen Dioxide and Nitrite

Hiramoto, Kazuyuki; Tomiyama, Susumu; Kikugawa, Kiyomi

doi:10.3109/10715769709065790

Cited by 22 publications

(11 citation statements)

References 17 publications

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“…This is consistent with findings in our laboratory that NOX-101 reduces the increase in plasma nitrate plus nitrite during cardiac allograft rejection [59]. We believe that the property of NOX-101 to scavenge NO is relatively specific as electron spin resonance spectroscopy confirms that similar derivatives bind nitrite and nitrogen dioxide with only 2±3 % efficiency and do not bind nitrate or peroxynitrite [60].…”

Section: Discussionsupporting

confidence: 80%

Long-term treatment in vivo with NOX-101, a scavenger of nitric oxide, prevents diabetes-induced endothelial dysfunction

1998

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Considerable evidence using experimental models [1±5] have shown that diabetes mellitus is an independent risk factor for the development of impaired endothelium-dependent relaxation ± that is, endothelial dysfunction. This defect has been confirmed in Type I (insulin-dependent) [6,7] and Type II (non-insulindependent) [8] diabetic patients. The factor(s) which contribute to endothelial dysfunction in diabetic patients is not known but data derived in experimental models have suggested several possibilities including: (a) concurrent release of an endothelium-derived constricting factor arising from the cyclooxygenase pathway [9,10] Summary Substantial evidence exists that diabetes results in impaired endothelial dysfunction suggesting diminished nitric oxide production from diabetic endothelium. It is not known what factors contribute to the development of this defect. In this study, we tested whether chronic treatment in vivo with NOX-101, a water-soluble nitric oxide scavenger, prevents endothelial dysfunction in diabetes. Sprague-Dawley rats were made diabetic by an intravenous injection of streptozotocin. A subgroup of control or diabetic animals received twice daily subcutaneous injections of 80 mg/kg NOX-101 beginning at 48 h after streptozotocin was injected and throughout 8 weeks of diabetes. Body weights and glucose concentrations were monitored weekly. At the end of 8 weeks, blood glucose and glycosylated haemoglobin was raised in diabetic rats but serum insulin concentrations were reduced. Treatment with NOX-101 did not alter glucose or insulin concentrations in control or diabetic rats; however, total glycosylated haemoglobin was partially reduced compared with untreated rats. In a subgroup of 2-week diabetic and age-matched rats fasted for 24 h, NOX-101 abolished total urinary nitrate plus nitrite (an index of nitric oxide production in vivo). In isolated tissue baths, relaxation to the endothelium-dependent vasodilator, acetylcholine, was impaired in diabetic aortic rings and relaxation to nitroglycerin was unaltered. Treatment of control rats with NOX-101 did not alter maximum relaxation to acetylcholine but shifted the response curve slightly to the right. In contrast in diabetic rats, NOX-101 prevented the impairment in endothelium-dependent relaxation but had no effect on relaxation induced by nitroglycerin. These data suggest the possibility that diabetes-induced endothelial dysfunction in diabetes results, in part, from a paradoxical increase in nitric oxide production during the course of the disease. This suggests a novel pathway of vascular complications. [Diabetologia (1998

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Section: Discussionsupporting

confidence: 80%

Long-term treatment in vivo with NOX-101, a scavenger of nitric oxide, prevents diabetes-induced endothelial dysfunction

1998

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“…This setup (Fig. 1A) was designed to isolate the reaction solution in the purging vessel from the spin trap and thus avoid any possible perturbation caused by the reaction of (MGD) with nitrite or with the enzyme (16,17). Samples from purging vessel 2 were aliquoted at desired times for EPR measurements.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the Effects of Oxygen on Xanthine Oxidase-mediated Nitric Oxide Formation

Samouilov

et al. 2004

Journal of Biological Chemistry

132

144

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Under anaerobic conditions, xanthine oxidase (XO)-catalyzed nitrite reduction can be an important source of nitric oxide (NO). However, questions remain regarding whether significant XO-mediated NO generation also occurs under aerobic conditions. Therefore, electron paramagnetic resonance, chemiluminescence NO-analyzer, and NO-electrode studies were performed to characterize the kinetics and magnitude of XO-mediated nitrite reduction as a function of oxygen tension. With substrates xanthine or 2,3-dihydroxybenz-aldehyde that provide electrons to XO at the molybdenum site, the rate of NO production followed Michaelis-Menten kinetics, and oxygen functioned as a competitive inhibitor of nitrite reduction. However, with flavin-adenine dinucleotide site-binding substrate NADH as electron donor, aerobic NO production was maintained at more than 70% of anaerobic levels, and binding of NADH to the flavin-adenine dinucleotide site seemed to prevent oxygen binding. Therefore, under aerobic conditions, NADH would be the main electron donor for XO-catalyzed NO production in tissues. Studies of the pH dependence of NO formation indicated that lower pH values decrease oxygen reduction but greatly increase nitrite reduction, facilitating NO generation. Isotope tracer studies demonstrated that XO-mediated NO formation occurs in normoxic and hypoxic heart tissue. Thus, XO-mediated NO generation occurs under aerobic conditions and is regulated by oxygen tension, pH, nitrite, and reducing substrate concentrations. Nitric oxide (NO)1 is a free radical endogenously produced in biological tissues and is an important regulator of numerous biological functions (1-4). NO can also cause cellular injury by means of reaction with superoxide to form the potent oxidant peroxynitrite (5-7). Specific nitric oxide synthase (NOS) enzymes have been generally considered to be the primary source of NO in biological systems. These enzymes metabolize arginine to citrulline with the formation of NO, and oxygen is required for this process (8, 9). Under severe hypoxic conditions, such as those that occur in ischemic tissues, the NO production from NOS is impaired because of the lack of oxygen. In ischemic tissues, other factors including marked acidosis also impair the function of NOS. More recently, it has been demonstrated that there is another enzymatic pathway of NO generation that does not require oxygen. It has been shown that under anaerobic conditions, XO-mediated nitrite or nitrate reduction can be a prominent source of [10][11][12][13][14]. This pathway is also enhanced under the acidotic conditions that occur during ischemia. Such XO-mediated NO generation can serve as an alternative source of NO under the near anoxic conditions that occur with no-flow ischemia (13,14).Xanthine oxidase (XO) is a flavoprotein enzyme that is widely distributed in various mammalian tissues. In addition to its FAD binding site, it also has molybdenum and iron sulfur centers. XO plays important roles in both physiological and pathological conditions. It is well k...

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“…However, Hiramoto et al [36] recently claimed that the signals of dithiocarbamate-Fee + -NO could be observed immediately after NO (1 mM) was mixed with MGD-Fe 2 + complex, and the signals increased with the NO concentration and prolonged incubation time. At the same time, Alexandre et al [37] also observed NO adduct signals derived from nitrite, the NO production from the reaction of nitrite disproportion could be increased 100-fold under acidic conditions, but under normal physiological conditions (pH 7.4) only low NO production occurred.…”

Section: Discussionmentioning

confidence: 99%

Improved method to detect nitric oxide in biological systems

Zhang

Xiong

et al. 2001

Appl. Magn. Reson.

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In this work an improved method is described for using organic solvent extracting to detect nitric oxide. The partition coefficients of the diethylthiocarbamate (DETC)-Fe 2+ complex between different organic solvents and water, the signal intensity of the same NO trapping complex concentration in different organic solvents, and the extracting abilities of the organic solvents were determined. It was found that ethyl acetate was the optimal organic solvent. With ethyl acetate as extracting solvent, the (DETC) 2 -Fe"-NO complex was extracted from water phase to organic phase, and low concentration of nitric oxide in large volume could be detected by electron spin resonance (ESR) at room tem -p e r a t u r e . T h e E S R s i g n a l i n t e n s i t y h a d a g o o d l i n e a r r e l a t i o n s h i p w i t h t h e c o n c e n t r a t i o n o f n i t r i c o x i d e , at a signal-to-noise ratio of 2. The detection threshold of this method was improved to lower than 50 nM, which was more sensitive than the usually used method. The (DETC)z FeZ*-NO complex was stable in the dark at 0-4°C, and there was little change after days. Nitric oxide produced by cardiomyocytes cultured in media and other biological systems was firstly detected with this method.

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Appearance of Electron Spin Resonance Signals in the Interaction of Dithiocarbamate-Fe(II) with Nitrogen Dioxide and Nitrite

Cited by 22 publications

References 17 publications

Long-term treatment in vivo with NOX-101, a scavenger of nitric oxide, prevents diabetes-induced endothelial dysfunction

Long-term treatment in vivo with NOX-101, a scavenger of nitric oxide, prevents diabetes-induced endothelial dysfunction

Characterization of the Effects of Oxygen on Xanthine Oxidase-mediated Nitric Oxide Formation

Improved method to detect nitric oxide in biological systems

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