Complexes of Fe2+ with diethyldithiocarbamate or N-methyl-d-glucamine dithiocarbamate as traps of nitric oxide in animal tissues: comparative investigations

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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“…This class of compounds bind NO in solution forming iron-nitrosyl complexes and bind the excess NO produced during septic shock [24,25].…”

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confidence: 99%

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

1998

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“…1 shows the EPR spectrum of the hippocampal tissue of intact rats. In this spectrum, there is a typical triplet signal from the complex (DETC) -Fe -NO at the value of the gfactor, equal to 2.038 (Mikoyan et al 1997). Moreover, the signal of the (DETC) -Cu complex is presented in the same area.…”

Section: Resultsmentioning

confidence: 87%

“…Recently, one of the most effective methods for the detection and quantification of NO in biological tissues is the method of electron paramagnetic resonance (Vanin et al 2002Khramtsov andVolodarsky 1998). Using the technique of spin traps, it allows the detection of NO in low concentrations (Mikoyan et al 1997). We used the complex of Fe with diethyldithiocarbamate ((DETC) -Fe ) as a spin trap.…”

Section: Formation Of the Complex Of No With The Spin Trap In Rat Tismentioning

confidence: 99%

“…Tissue samples were immediately frozen in liquid nitrogen and transported under frozen conditions from Minsk to Kazan. In this state, the complex spin trap with NO ((DETC) -Fe -NO) was well preserved and the signal from the complex did not change for a month (Vanin et al 2002, Andrianov et al 2016, Mikoyan et al 1997. The measurements of the spectra of the complex (DETC) -Fe -NO were performed on the spectrometer ER 200 SRC Bruker in the X band (9.50 GHz) with the modulation of the magnetic field of 100kHz, the modulation of the amplitude of 2Hz, the microwave radiation power of 30mW, time constant of 200ms and the temperature of 77ºK in the Finger Dewar Bruker.…”

Section: Formation Of the Complex Of No With The Spin Trap In Rat Tismentioning

confidence: 99%

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Participation of NO-synthase in Control of Nitric Oxide Level in Rat Hippocampus after Modelling of Ischaemic and Haemorrhagic Insult

Гайнутдинов¹,

Pashkevich²,

Андрианов³

et al. 2017

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Electron paramagnetic resonance (EPR) was used as a method for recording the content of the nitric oxide (NO) in hippocampal tissues of intact rats and rats after modelling of ischaemic and haemorrhagic stroke. Based on direct measurements of NO by EPR spectroscopy, it was shown that, within 5 hours after the onset of symptoms of ischaemic and haemorrhagic stroke, the formation of NO in the hippocampus was reduced by a factor of 2-3 and this reduction was maintained for a period of between 24 and 72 hours. The results show that a systemic character of a decrease in the intensity of NO production during the modelling of ischaemic events in the brain reflects the effects of central dysregulation of the functions at the level of the whole organism such that it is appropriate to consider implementing the correction of the vital systems of the body in a stroke. It has indicated that non-selective NO-synthase blocker L-NAME reduced the low level of NO production by a factor of 3 by its administration within 72 hours after post-ischaemic and haemorrhagic stroke. It was discovered however that L-NAME returns the level of NO production to baseline (control) by its administration within 5 hours after ischaemia.

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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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Complexes of Fe2+ with diethyldithiocarbamate or N-methyl-d-glucamine dithiocarbamate as traps of nitric oxide in animal tissues: comparative investigations

Cited by 89 publications

References 18 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

Participation of NO-synthase in Control of Nitric Oxide Level in Rat Hippocampus after Modelling of Ischaemic and Haemorrhagic Insult

The complex role of iNOS in acutely rejecting cardiac transplants

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