DNIC

Dinitrosyl iron complexes (DNICs) stabilize nitric oxide in cells and tissues and constitute an important form of its storage and transportation. DNICs may comprise low-molecular-weight ligands, e.g., thiols, imidazole groups in chemical compounds with low molecular weight (LMWDNICs), or high-molecular-weight ligands, e.g., peptides or proteins (HMWDNICs). The aim of this study was to investigate the role of low- and high-molecular-weight ligands in DNIC formation. Lysosomal and proteasomal proteolysis was inhibited by specific inhibitors...

BACKGROUND: The dorsal reticular nucleus is a pain facilitatory area involved in the diffuse noxious inhibitory controls (DNIC), through opioidergic mechanisms that are poorly understood. We hypothesized that signaling of µ-opioid receptors is altered in this area at prolonged chronic inflammatory pain and that this accounts for the loss of DNIC occurring in this condition. METHODS: Monoarthritis was induced in male Wistar rats (n=5-9/group) by tibiotarsal injection of complete Freund's adjuvant...

The spinal dorsal horn (SDH) transmits sensory information from the periphery to the brain. Wide dynamic range (WDR) neurons within this relay site play a critical role in modulating and integrating peripheral sensory inputs, as well as the process of central sensitization during pathological pain. This group of spinal multi-receptive neurons has attracted considerable attention in pain research due to their capabilities for encoding the location and intensity of nociception. Meanwhile, transmission, processing, and modulation of incoming afferent information in WDR neurons also establish the underlying basis for investigating the integration of acupuncture and pain signals...

To understand the neuroscience of pain relief, one must know about the descending pain modulatory system. Neuronal pathways that originate in the brainstem and project to the spinal cord to modulate spinal neuronal activity provide a well-documented perspective on the mechanisms of analgesia that underpin pharmacological and nonpharmacological treatment options for people with musculoskeletal pain. Peripheral stimuli or signals from the cortex and subcortical regions of the brain can trigger the descending pain modulatory system (DPMS)...

The coupled NO-vibrational peaks [IR νNO 1775 s, 1716 vs, 1668 vs cm-1 (THF)] between two adjacent [Fe(NO)2 ] groups implicate the electron delocalization nature of the singly O -phenoxide-bridged dinuclear dinitrosyliron complex (DNIC) [Fe(NO)2 (μ-ON2 Me )Fe(NO)2 ] ( 1 ). Electronic interplay between [Fe(NO)2 ] units and [ON2 Me ]- ligand in DNIC 1 rationalizes that "hard" O -phenoxide moiety polarizes iron center(s) of [Fe(NO)2 ] unit(s) to enforce a "constrained" π-conjugation system acting as an electron reservoir to bestow the spin-frustrated {Fe(NO)2 }9 -{Fe(NO)2 }9 -[· ON2 Me ]2- electron configuration ( S total = 1/2)...

DNIC can be formed in aqueous media in the absence of thiols via mechanisms that depend exclusively on Fe(II) and NO. However, these reactions do not take place at intracellular concentrations of Fe(II) and NO, reinforcing the relevance of thiols to assist Fe(II) to Fe(I) reduction during DNIC formation in biological media.

Metabolism of nitric oxide (NO) donors: dinitrosyl iron complexes (DNIC), nitrosothiols (RSNO), and nitroprusside was studied on a chick embryo model. The obtained results give reason to assume that DNIC constituting the main pool of nitroso compounds in the vast majority of tissues are NO donors immediately interacting with the physiological target of NO, and other NO donors can perform this function after their transformation into DNIC. NO is released from DNIC not spontaneously, but under a joint influence of a factor destroying the complex and a target having chemical affinity for NO...

Nanosized zerovalent iron (NZVI) Fe@Fe 3 O 4 with a core-shell structure derived from photocatalytic MeOH aqueous solution of dinitrosyl iron complex (DNIC) [(N3 MDA)Fe(NO)2 ] (N3 MDA = N , N -dimethyl-2-(((1-methyl-1 H -imidazole-2-yl)methylene)amino)ethane-1-amine) ( 1-N 3 MDA ), eosin Y, and triethylamine (TEA) is demonstrated. The NZVI Fe@Fe 3 O 4 core shows a high percentage of zerovalent iron (Fe0 %) and is stabilized by a hydrophobic organic support formed through the photodegradation of eosin Y hybridized with the N3 MDA ligand...

Dinitrosyl iron complexes (DNICs) are important physiological derivatives of nitric oxide. These complexes have a wide range of biological activities, with antioxidant and antiradical ones being of particular interest and importance. We studied the interaction between DNICs associated with the dipeptide L-carnosine or serum albumin and prooxidants under conditions mimicking oxidative stress. The ligands of these DNICs were histidine residues of carnosine or His39 and Cys34 in bovine serum albumin. Carnosine-bound DNICs reduced the level of piperazine free radicals in the reaction system containing tert -butyl hydroperoxide ( t -BOOH), bivalent iron ions, a nitroxyl anion donor (Angeli's salt), and HEPES buffer...

Experimental data were summarized to assume that dinitrosyl iron complexes (DNICs) with thiol-containing ligands are an endogenous "working form" of the nitric oxide (NO) system in living organisms. DNICs can function as donors of both neutral NO molecules, which are responsible for positive regulatory effects of the NO system on various physiological and biochemical processes in humans and animals, and nitrosonium cations (NO^(+)), which are responsible mostly for negative cytotoxic activity of the system...

Flavodiiron nitric oxide reductases (FNORs) equip pathogens with resistance to nitric oxide (NO), an important immune defense agent in mammals, allowing these pathogens to proliferate in the human body, potentially causing chronic infections. Understanding the mechanism of how FNORs mediate the reduction of NO contributes to the greater goal of developing new therapeutic approaches against drug-resistant strains. Recent density functional theory calculations suggest that a second coordination sphere (SCS) tyrosine residue provides a hydrogen bond that is critical for the reduction of NO to N2 O at the active site of FNORs [J...

We recently developed a combination of four chemiluminescence-based assays for selective detection of different nitric oxide (NO) metabolites, including nitrite, S-nitrosothiols (SNOs), heme-nitrosyl (heme-NO), and dinitrosyl iron complexes (DNICs). However, these NO species (NOx) may be under dynamic equilibria during sample handling, which affects the final determination made from the readout of assays. Using fetal and maternal sheep from low and high altitudes (300 and 3801 m, respectively) as models of different NOx levels and compositions, we tested the hypothesis that sample handling introduces artifacts in chemiluminescence assays of NOx...

Through nitrosylation of [Fe-S] proteins, or the chelatable iron pool, a dinitrosyl iron unit (DNIU) [Fe(NO)2 ] embedded in the form of low-molecular-weight/protein-bound dinitrosyl iron complexes (DNICs) was discovered as a metallocofactor assembled under inflammatory conditions with elevated levels of nitric oxide (NO) and superoxide (O2 - ). In an attempt to gain biomimetic insights into the unexplored transformations of the DNIU under inflammation, we investigated the reactivity toward O2 - by a series of DNICs [(NO)2 Fe(μ-Me Pyr)2 Fe(NO)2 ] ( 1 ) and [(NO)2 Fe(μ-SEt)2 Fe(NO)2 ] ( 3 )...

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, memory loss, and behavioral deficits. β-amyloid1-42 (Aβ1-42 ) aggregation is a significant cause of the pathogenesis in AD. Despite the numerous types of research, the current treatment efficacy remains insufficient. Hence, a novel therapeutic strategy is required. Nitric oxide (NO) is a multifunctional gaseous molecule. NO displays a neuroprotective role in the central nervous system by inhibiting the Aβ aggregation and rescuing memory and learning deficit through the NO signaling pathway...

Craniofacial/jawbone deformities remain a significant clinical challenge in restoring facial/dental functions and esthetics. Despite the reported therapeutics for clinical bone tissue regeneration, the bioavailability issue of autografts and limited regeneration efficacy of xenografts/synthetic bone substitutes, however, inspire continued efforts towards functional conjugation and improvement of bioactive bone graft materials. Regarding the potential of nitric oxide (NO) in tissue engineering, herein, functional conjugation of NO-delivery dinitrosyl iron complex (DNIC) and osteoconductive bone graft materials was performed to optimize the spatiotemporal control over the delivery of NO and to activate synergistic osteogenesis and angiogenesis in rat calvaria bone defects...

Bacterial NO Reductase (NorBC or cNOR) is a membrane-bound enzyme found in denitrifying bacteria that catalyzes the two-electron reduction of NO to N2 O and water. The mechanism by which NorBC operates is highly debated, due to the fact that this enzyme is difficult to work with, and no intermediates of the NO reduction reaction could have been identified so far. The unique active site of NorBC consists of a heme b3 /non-heme FeB diiron center. Synthetic model complexes provide the opportunity to obtain insight into possible mechanistic alternatives for this enzyme...

The application of a noxious stimulus reduces the perception of other noxious stimuli, which can be assessed by an experimental method called "counterirritation." The question arises whether this type of inhibition also affects the processing of other aversive (but not nociceptive) stimuli, such as loud tones. If aversiveness or, in other words, negative emotional valence qualifies a stimulus to be affected by counterirritation, the general emotional context may also play a role in modulating counterirritation effects...

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...