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Sumit Sahni, Jason R Hickok, Douglas D Thomas
The chelatable iron pool (CIP) is a small but chemically significant fraction of total cellular iron. While this dynamic population of iron is limited, it is redox active and capable of generating reactive oxygen species (ROS) that can lead to oxidative stress which is associated with various pathologies. Nitric oxide (•NO), is a free radical signalling molecule that regulates numerous physiological and pathological conditions. We have previously shown that macrophages exposed to endogenously generated or exogenously administered nitric oxide (•NO) results in its interaction with CIP to form dinitrosyliron complexes with thiol containing ligands (DNICs)...
March 6, 2018: Nitric Oxide: Biology and Chemistry
Konstantin B Shumaev, Arina L Dudylina, Marina V Ivanova, Igor S Pugachenko, Enno K Ruuge
Mitochondria are widely known as a major source of reactive oxygen and nitrogen species for the cardiovascular system. Numerous studies established that superoxide anion radical production by heart mitochondria is only slightly suppressed under conditions of deep hypoxia, but is completely blocked under anoxia. It was found also that dinitrosyl iron complexes (DNIC) compare favourably with other physiologically active derivatives of nitric oxide (NO). DNIC with glutathione effectively scavenge superoxide radicals generated by mitochondria at different partial pressures of oxygen...
February 22, 2018: BioFactors
Irina Studneva, Valentin Shulzhenko, Oksana Veselova, Oleg Pisarenko
The maintenance of nitric oxide (NO) bioavailability has been recognized as an important component of myocardial protection during cardiac surgery. This study was designed to evaluate the efficacy of using two NO-donating compounds in cardioplegia and reperfusion: (i) a modified peptide apelin-12 (MA12) that activates endothelial NO synthase (eNOS) and (ii) dinitrosyl iron complexes with reduced glutathione (DNIC-GS), a natural NO vehicle. Isolated perfused working rat hearts were subjected to normothermic global ischemia and reperfusion...
February 20, 2018: Journal of Physiology and Biochemistry
Julie Bonapace, Guy-Paul Gagné, Nils Chaillet, Raymonde Gagnon, Emmanuelle Hébert, Sarah Buckley
OBJECTIVE: To review the evidence relating to nonpharmacological approaches in the management of pain during labour and delivery. To formulate recommendations for the usage of nonpharmacological approaches to pain management. OPTIONS: Nonpharmacological methods available for pain management during labour and delivery exist. These should be included in the counselling and care of women. EVIDENCE: PubMed and Medline were searched for articles in French and English on subjects related to "breastfeeding," "pain," "epidural," "anaesthesia," "analgesia," "labour," "labor," and combined with "gate control theory," "alternative therapies," "massage," "position," "mobility," "TENS," "bathing," "DNIC," "acupuncture," "acupressure," "sterile water injection," "higher center," "control mind," "cognitive structuring," "holistic health," "complementary therapy(ies)," "breathing," "relaxation," "mental imagery," "visualization," "mind focusing," "hypnosis," "auto-hypnosis," "sophrology," "mind and body interventions," "music," "odors," "biofeedback," "Lamaze," "Bonapace," "prenatal training," "gymnastic," "chanting," "haptonomy," "environment," "transcutaneous electrical stimulus-stimulation," "antenatal education," "support," "continuous support," "psychosocial support," "psychosomatic medicine," "supportive care," "companion," "intrapartum care," "nurse," "midwife(ves)," "father," "doula," "caregiver," " hormones," "oxytocin," "endorphin," "prolactin," "catecholamine," "adrenaline," and "noradrenaline" from 1990 to December 2015...
February 2018: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
Karen-Amanda Irvine, Peyman Sahbaie, De-Yong Liang, David Clark
Chronic pain is a common consequence of traumatic brain injury (TBI) that can increase a patient's suffering and pose a significant challenge to rehabilitative efforts. Unfortunately, the mechanisms linking TBI to pain are poorly understood and specific treatments for TBI-related pain are still lacking. Our lab has shown that TBI causes pain sensitization in areas distant to the site of primary injury, and that changes in spinal gene expression may underlie this sensitization1, 2. The aim of this study was to examine the roles that pain modulatory pathways descending from the brainstem play in pain after TBI...
January 26, 2018: Journal of Neurotrauma
Kelsey M Nation, Milena De Felice, Pablo I Hernandez, David W Dodick, Volker Neugebauer, Edita Navratilova, Frank Porreca
The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus)...
January 23, 2018: Pain
Ambar Banerjee, Souloke Sen, Ankan Paul
Though dinitrosyl-iron complexes (DNICs) are largely believed to act as NO carriers, several experiments on model DNICs have suggested that they can also act as nitrating agents in presence of dioxygen. Oxygen activation by DNICs has been implicated as a possible route for protein tyrosine nitration (PTN), which leads to neurodegenerative disorders. Herein using static and dynamic theoretical techniques we unravel a previously unknown dual state mechanistic paradigm for dioxygen activation of a biomimetic nitrating DNIC complex leading to phenolic nitration...
March 2, 2018: Chemistry: a European Journal
Douglas D Thomas, Catherine Corey, Jason Hickok, Yinna Wang, Sruti Shiva
Nitrite represents an endocrine reserve of bioavailable nitric oxide (NO) that mediates a number of physiological responses including conferral of cytoprotection after ischemia/reperfusion (I/R). It has long been known that nitrite can react with non-heme iron to form dinitrosyliron complexes (DNIC). However, it remains unclear how quickly nitrite-dependent DNIC form in vivo, whether formation kinetics differ from that of NO-dependent DNIC, and whether DNIC play a role in the cytoprotective effects of nitrite...
May 2018: Redox Biology
N P Akentieva, N A Sanina, A R Gizatullin, N Y Shmatko, N S Goryachev, N I Shkondina, T R Prikhodchenko, S M Aldoshin
The effect of synthetic analogues of dinitrosyl mononuclear iron complexes (DNICs) with functional sulfur-containing ligands (NO donors) on the activity of myeloperoxidase (MPO) was studied, and their efficiency was evaluated. It was shown that the enzyme MPO is the molecular target of DNICs. It was found that six DNICs inhibited the activity of MPO and one compound potentiated it. The evaluation of their efficiency showed that two DNICs effectively inhibited the activity of MPO by 50% at IC50 = 2 × 10-4 M and IC50 = 5 × 10-7 M...
November 2017: Doklady. Biochemistry and Biophysics
Kazuo Kobayashi
Bacteria possess molecular biosensors that enable responses to a variety of stressful conditions, including oxidative stress, toxic compounds, and interactions with other organisms, through elaborately coordinated regulation of gene expression. In Escherichia coli and related bacteria, the transcription factor SoxR functions as a sensor of oxidative stress and nitric oxide (NO). SoxR protein contains a [2Fe-2S] cluster essential for its transcription-enhancing activity, which is regulated by redox changes in the [2Fe-2S] cluster...
June 21, 2017: Accounts of Chemical Research
Kirsty Bannister, A H Dickenson
Descending controls, comprising pathways that originate in midbrain and brainstem regions and project onto the spinal cord, have long been recognised as key links in the multiple neural networks that interact to produce the overall pain experience. There is clear evidence from preclinical and clinical studies that both peripheral and central sensitisation play important roles in determining the level of pain perceived. Much emphasis has been put on spinal cord mechanisms in central excitability, but it is now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems...
July 1, 2017: Journal of Physiology
Z Kovacevic, S Sahni, H Lok, M J Davies, D A Wink, D R Richardson
We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores and transports NO as dinitrosyl-dithiol-iron complexes (DNICs) composed of iron, NO and glutathione (GSH). Hence, this gas with contrasting anti- and pro-tumor effects, which has been assumed to be freely diffusible, is a tightly-regulated species in M1-MØs...
May 2017: Biochimica et Biophysica Acta
Anatoly F Vanin, Rostislav R Borodulin, Vasak D Mikoyan
Two approaches to the synthesis of dinitrosyl iron complexes (DNIC) with glutathione and l-cysteine in aqueous solutions based on the use of gaseous NO and appropriate S-nitrosothiols, viz., S-nitrosoglutathione (GS-NO) or S-nitrosocysteine (Cys-NO), respectively, are considered. A schematic representation of a vacuum unit for generation and accumulation of gaseous NO purified from the NO2 admixture and its application for obtaining aqueous solutions of DNIC in a Thunberg apparatus is given. To achieve this, a solution of bivalent iron in distilled water is loaded into the upper chamber of the Thunberg apparatus, while the thiol solution in an appropriate buffer (рН 7...
June 1, 2017: Nitric Oxide: Biology and Chemistry
Agnes Keszler, Anne R Diers, Zhen Ding, Neil Hogg
Dinitrosyl iron complexes (DNIC) spontaneously form in aqueous solutions of Fe(II), nitric oxide (NO), and various anions. They exist as an equilibrium between diamagnetic, dimeric (bi-DNIC) and paramagnetic, monomeric (mono-DNIC) forms. Thiolate groups (e.g., on glutathione or protein cysteine residues) are the most biologically relevant anions to coordinate to Fe(II). Low molecular weight DNIC have previously been suggested to be important mediators of NO biology in cells, and emerging literature supports their role in the control of iron-dependent cellular processes...
May 1, 2017: Nitric Oxide: Biology and Chemistry
Randara Pulukkody, Rachel B Chupik, Steven K Montalvo, Sarosh Khan, Nattamai Bhuvanesh, Soon-Mi Lim, Marcetta Y Darensbourg
Both monomeric and dimeric tetraacetylglucose-containing {Fe(NO)2 }9 dinitrosyl iron complexes (DNICs) were prepared and examined for NO release in the presence of both chemical NO-trapping agents and endothelial cells.
January 17, 2017: Chemical Communications: Chem Comm
Chun-Hung Ke, Chien-Hong Chen, Ming-Li Tsai, Hsuan-Chi Wang, Fu-Te Tsai, Yun-Wei Chiang, Wei-Chih Shih, D Scott Bohle, Wen-Feng Liaw
To carry and deliver nitric oxide with a controlled redox state and rate is crucial for its pharmaceutical/medicinal applications. In this study, the capability of cationic {Fe(NO)2}(9) dinitrosyl iron complexes (DNICs) [((R)DDB)Fe(NO)2](+) (R = Me, Et, Iso; (R)DDB = N,N'-bis(2,6-dialkylphenyl)-1,4-diaza-2,3-dimethyl-1,3-butadiene) carrying nearly unperturbed nitric oxide radical to form [((R)DDB)Fe(NO)2((•)NO)](+) was demonstrated and characterized by IR, UV-vis, EPR, NMR, and single-crystal X-ray diffractions...
January 11, 2017: Journal of the American Chemical Society
Vasak D Mikoyan, Evgeniya N Burgova, Rostislav R Borodulin, Anatoly F Vanin
It has been established that treatment of mice with sodium nitrite, S-nitrosoglutathione and the water-soluble nitroglycerine derivative isosorbide dinitrate (ISDN) as NO donors initiates in vivo synthesis of significant amounts of EPR-silent binuclear dinitrosyl iron complexes (B-DNIC) with thiol-containing ligands in the liver and other tissues of experimental mice. This effect is especially apparent if NO donors are administered to mice simultaneously with the Fe(2+)-citrate complex. Similar results were obtained in experiments on isolated liver and other mouse tissues treated with gaseous NО in vitro and during stimulation of endogenous NO synthesis in the presence of inducible NO synthase...
January 30, 2017: Nitric Oxide: Biology and Chemistry
K Bannister, S Lockwood, L Goncalves, R Patel, A H Dickenson
BACKGROUND: Following neuropathy α2-adrenoceptor-mediated diffuse noxious inhibitory controls (DNIC), whereby a noxious conditioning stimulus inhibits the activity of spinal wide dynamic range (WDR) neurons, are abolished, and spinal 5-HT7 receptor densities are increased. Here, we manipulate spinal 5-HT content in spinal nerve ligated (SNL) animals and investigate which 5-HT receptor mediated actions predominate. METHODS: Using in vivo electrophysiology we recorded WDR neuronal responses to von frey filaments applied to the hind paw before, and concurrent to, a noxious ear pinch (the conditioning stimulus) in isoflurane-anaesthetised rats...
April 2017: European Journal of Pain: EJP
Konstantin B Shumaev, Olga V Kosmachevskaya, Elvira I Nasybullina, Sergey V Gromov, Alexander A Novikov, Alexey F Topunov
Dinitrosyl iron complexes (DNICs) are physiological NO derivatives and account for many NO functions in biology. Polyfunctional dipeptide carnosine (beta-alanyl-L-histidine) is considered to be a very promising pharmacological agent. It was shown that in the system containing carnosine, iron ions and Angeli's salt, a new type of DNICs bound with carnosine as ligand {(carnosine)2-Fe-(NO)2}, was formed. We studied how the carbonyl compound methylglyoxal influenced this process. Carnosine-bound DNICs appear to be one of the cell's adaptation mechanisms when the amount of reactive carbonyl compounds increases at hyperglycemia...
January 2017: Journal of Biological Inorganic Chemistry: JBIC
Hiu Chuen Lok, Sumit Sahni, Patric J Jansson, Zaklina Kovacevic, Clare L Hawkins, Des R Richardson
Nitric oxide (NO) is integral to macrophage cytotoxicity against tumors due to its ability to induce iron release from cancer cells. However, the mechanism for how activated macrophages protect themselves from endogenous NO remains unknown. We previously demonstrated by using tumor cells that glutathione S-transferase P1 (GSTP1) sequesters NO as dinitrosyl-dithiol iron complexes (DNICs) and inhibits NO-mediated iron release from cells via the transporter multidrug resistance protein 1 (MRP1/ABCC1). These prior studies also showed that MRP1 and GSTP1 protect tumor cells against NO cytotoxicity, which parallels their roles in defending cancer cells from cytotoxic drugs...
December 30, 2016: Journal of Biological Chemistry
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