DNIC

The loss of diffuse noxious inhibitory controls (DNIC) is recognized as a predictor of chronic pain. Mechanistically, DNIC produces analgesia by a heterotopically applied conditioning-noxious stimulus (CS) and yet underexplored descending modulatory inputs. Here, we aimed at studying DNIC in monoarthritis (MA) by exploring the spinal component of the descending serotonergic system, specifically 5-hydroxytryptamine 3 receptors (5-HT3R). MA was induced in male Wistar rats by tibiotarsal injection of complete Freund's adjuvant...

Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound healing effects of binuclear dinitrosyl iron complexes with glutathione (B-DNIC-GSH) and NO-containing gas flow (NO-CGF) at their optimal NO doses (0.04 mmol for B-DNIC-GSH and 1.0 mmol for NO-CGF per 1 cm2 ) in a rat full-thickness wound model over a 3-week period...

Fibrosis is an excessive accumulation of extracellular matrix (ECM) that may cause severe organ dysfunction. Nitric oxide (NO), a multifunctional gaseous signaling molecule, may inhibit fibrosis, and delivery of NO may serve as a potential antifibrotic strategy. However, major limitations in the application of NO to treat fibrotic diseases include its nonspecificity, short half-life and low availability in fibrotic tissue. Herein, we aimed to develop a stimuli-responsive drug carrier to deliver NO to halt kidney fibrosis...

The central nervous system houses naturally occurring pathways that project from the brain to modulate spinal neuronal activity. The noradrenergic locus coeruleus (the A6 nucleus) originates such a descending control whose influence on pain modulation encompasses an interaction with a spinally projecting non-cerulean noradrenergic cell group. Hypothesising the origin of an endogenous pain inhibitory pathway, our aim was to identify this cell group. A5 and A7 noradrenergic nuclei also spinally project. We probed their activity utilising an array of optogenetic manipulation techniques during in vivo electrophysiological experimentation...

Carbonyl stress occurs when reactive carbonyl compounds (RCC), such as reducing sugars, dicarbonyls etc., accumulate in the organism. The interaction of RCC carbonyl groups with amino groups of molecules is called the Maillard reaction. One of the most active RCCs is α-dicarbonyl methylglyoxal (MG) that modifies biomolecules forming non-enzymatic glycation products. Organic free radicals are formed in the reaction between MG and lysine or Nα-acetyllysine. S-nitrosothiols and nitric oxide (• NO) donor PAPA NONOate increased the yield of organic free radical intermediates, while other • NO-derived metabolites, namely, nitroxyl anion and dinitrosyl iron complexes (DNICs) decreased it...

This study demonstrates a bacteriostatic effect of binuclear dinitrosyl iron complexes with glutathione on Escherichia coli TN300 cells. It has been quantified by the colony formation assay. The bacteriostatic effect exerted by these complexes increases considerably in the presence of diethyldithiocarbamate. Our results suggest that this effect is caused by the intense release of nitrosonium cations, NO+ , from the complexes, which decompose under the action of diethyldithiocarbamate. A similar effect is observed when E...

Glutathione-S-transferases (GSTs) are phase II detoxification isozymes that conjugate glutathione (GSH) to xenobiotics and also suppress redox stress. It was suggested that GSTs have evolved not to enhance their GSH affinity, but to better interact with and metabolize cytotoxic nitric oxide (NO). The interactions between NO and GSTs involve their ability to bind and store NO as dinitrosyl-dithiol iron complexes (DNICs) within cells. Additionally, the association of GSTP1 with inducible nitric oxide synthase (iNOS) results in its inhibition...

The proposed in our studies mechanism of dinitrosyl iron complex (DNIC) formation through the main step of disproportionation of two NO molecules in complex with Fe2+ ion leads to emergence of the resonance structure of dinitrosyl-iron fragment of DNIC, [Fe2+(NO)(NO+ )]. The latter allowed suggesting capacity of these complexes to function as donor of both neutral NO molecules as well as nitrosonium cations (NO+ ), which has been demonstrated in experiments. Analysis of biological activity of DNICs with thiol-containing ligands presented in this review demonstrates that NO molecules and nitrosonium cations released from the complexes exert respectively positive (regulatory) and negative (cytotoxic) effects on living organisms...

In this work a new donor of nitric oxide (NO) with antibacterial properties, namely nitrosyl iron complex of [Fe(C6 H5 C-SNH2 )2 (NO)2 ][Fe(C6 H5 C-SNH2 )(S2 O3 )(NO)2 ] composition (complex I ), has been synthesized and studied. Complex I was produced by the reduction of the aqueous solution of [Fe2 (S2 O3 )2 (NO)2 ]2- dianion by the thiosulfate, with the further treatment of the mixture by the acidified alcohol solution of thiobenzamide. Based on the structural study of I (X-ray analysis, quantum chemical calculations by NBO and QTAIM methods in the frame of DFT), the data were obtained on the presence of the NO…NO interactions, which stabilize the DNIC dimer in the solid phase...

A dimeric dithiolate-bridged species, [Fe(NO)(PS2)]2 ( 1 ) containing two {FeNO}7 units, can be isolated by treating [Fe(CO)2 (NO)2 ] with PS2H2 (PS2H2 = bis(2-dimercaptophenyl)phenylphosphine). Crystallographic studies reveal the syn-configuration of NO units and the bridging thiolates in the butterfly shape of the 2Fe2S core. Addition of PPh3 to the solution of dinuclear 1 leads to the formation of mononuclear {FeNO}7 [Fe(NO)(PS2)(PPh3 )] ( 2 ) that shows electrochemical responses similar to those of 1 . One-electron reduction of 1 with Cp*2 Co or KC8 results in the isolation of thiolate-bridged bimetallic DNIC, [(PS2)Fe(μ-PS2)Fe(NO)2 ]- ([ 3 ]- ), confirmed by several spectroscopies including single-crystal X-ray diffraction studies...

Traumatic brain injury (TBI) is a significant public health concern, with the majority of injuries being mild. Many TBI victims experience chronic pain. Unfortunately, the mechanisms underlying pain after TBI are poorly understood. Here we examined the contribution of spinal monoamine signaling to dysfunctional descending pain modulation after TBI. For these studies we used a well-characterized concussive model of mild TBI. Measurements included mechanical allodynia, the efficacy of diffuse noxious inhibitory control (DNIC) endogenous pain control pathways and lumber norepinephrine and serotonin levels...

Dinitrosyl iron complexes (DNICs) are a depot and potential source of free NO in organisms. Their synthetic analog, N-ethylthiourea DNIC [Fe(SC(NH2 )(NHC2 H5 ))2 (NO)2 ]+ Cl- ∙[Fe(SC(NH2 )(NHC2 H5 ))Cl(NO)2 ]0 (complex 1), as cardioprotective and cytostatic agent is a promising prodrug for the treatment of socially relevant diseases. In this work, transformation mechanism of complex 1 has been studied in anaerobic aqueous solution (pH = 7.0), DMSO, and ethanol. It was shown that the solvent has a significant effect on the decomposition of complex...

Hemifacial spasm (HFS) and temporomandibular joint (TMJ) pain are common facial diseases which cause depression, anxiety, insomnia, and poor quality of life. However, currently there are still no effective therapies to treat HFS and TMJ. Electroacupuncture (EA) has advantages of safety, rapid work, easy operation and convenience. Here, we reported a case of a 50-year-old woman who presented with irregular spasm of eyelids and facial muscles on the left side, and TMJ pain on the right side. The patient had been treated with carbamazepine (20mg per day) and alternative therapies for a year, but still not much improvement in the symptoms...

Placental nitric oxide (NO) is critical for maintaining perfusion in the maternal-fetal-placental circulation during normal pregnancy. NO and its many metabolites are also increased in pregnancies complicated by maternal inflammation such as preeclampsia, fetal growth restriction, gestational diabetes, and bacterial infection. However, it is unclear how increased levels of NO or its metabolites affect placental function or how the placenta deals with excessive levels of NO or its metabolites. Since there is uncertainty over the direction of change in plasma levels of NO metabolites in preeclampsia, we measured the levels of these metabolites at the placental tissue level...

The cytotoxic activity of a series of dinitrosyl iron complexes (DNICs) with thioureas against cells of different origin has been studied in this work. The cytotoxicity of the studied DNICs proved to be substantially different depending on the structure of the complexes and cell line. Complexes with thiourea and 1,3-dimethylthiourea were found to induce notable cell death in different cell lines of both cancerous and non-cancerous origin, while the N -ethylthiourea-bearing complex induced cell death in cells derived from brain tumors...

S-nitrosothiols (SNO), dinitrosyl iron complexes (DNIC), and nitroglycerine (NTG) dilate vessels via activation of soluble guanylyl cyclase (sGC) in vascular smooth muscle cells. Although these compounds are often considered to be nitric oxide (NO) donors, attempts to ascribe their vasodilatory activity to NO-donating properties have failed. Even more puzzling, many of these compounds have vasodilatory potency comparable to or even greater than that of NO itself, despite low membrane permeability. This raises the question: How do these NO adducts activate cytosolic sGC when their NO moiety is still outside the cell? In this review, we classify these compounds as 'nitrodilators', defined by their potent NO-mimetic vasoactivities despite not releasing requisite amounts of free NO...

Disruption of endogenous pain control mechanisms including descending pain inhibition has been linked to several forms of pain including chronic pain after traumatic brain injury (TBI). The locus coeruleus (LC) is the principal noradrenergic (NA) nucleus participating in descending pain inhibition. We therefore hypothesized that selectively stimulating LC neurons would reduce nociception after TBI. All experiments used a well-characterized rat lateral fluid percussion model of TBI. NA neurons were stimulated by administering clozapine N-oxide (CNO) to rats selectively expressing a designer receptor exclusively activated by designer drug (DREADD) viral construct in their LC's...

High-molecular-weight dinitrosyl iron complexes (DNICs) are formed in living systems and are a stable depot of nitrogen monoxide (NO). In this work, using experimental and theoretical methods, we investigated the interaction of their synthetic analog, a promising cardiotropic complex of the composition [Fe(SC(NH2 )2 )2 (NO)2 ]2 [Fe2 (S2 O3 )2 (NO)4 ], with bovine serum albumin (BSA) in aqueous aerobic solutions. We suggested that, under these conditions, the decomposition product of the initial complex with oxygen, the [Fe(NO)(NO2 )]+ fragment, can bind in the hydrophobic pocket of the protein...

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe2 (μ-SCH2 CH2 COOH)2 (NO)4 ] ( DNIC-2 ) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO...

BACKGROUND: The tree of heaven root weevil, Eucryptorrhynchus scrobiculatus (TRW), is one of the most damaging pests of Ailanthus altissima in China. A limited number of studies have examined the effects of different variables on the population density of TRW adults. We investigated the relative impacts of the diameter at breast height of host trees (DBH), number of tree species in plots (NTS), weed coverage rate of the host tree base (WCR), plot area (PA), distance from plots to the nearest farmland (DNF), nearest human community (DNHC), nearest irrigation canal (DNIC), and nearest road (DNR) on TRW population density...