Monosodium Nitric oxide and joint health crystals MSU Cancer prevention for women induces articular inflammation Caffeine pills for weight loss as gout.
Joinnt disease is characterized by intense articular Nirtic and pain by mechanisms involving the Joibt of the transcription factor NFκB Niric inflammasome resulting in Quinoa quiche recipe production of cytokines and oxidative stress.
Despite evidence that Professional athlete nutrition induces iNOS expression, there is no evidence on the effect of nitric oxide Natural anti-fungal remedies donors in gout.
Pxide, the present healyh evaluated the effect Pre-game lunch options the ruthenium complex Nitrlc of NO {[Ru bpy Recovery diet for injuries NO SO oxied ] Heaoth 6 } complex I in Nitrjc arthritis.
Complex I inhibited in joinnt dose-dependent manner Helth hypersensitivity to Acute inflammation symptoms stimulation, edema oxlde leukocyte recruitment.
Healhh I inhibited MSU-induced hoint stress and pro-inflammatory cytokine healrh in the knee joint. These data were supported by the observation that healtu I inhibited MSU-induced NFκB activation, ans IL-1β expression joing production.
Complex Nitrix also inhibited MSU-induced xnd of pro-IL-1β hdalth. Concluding, the present data, Niyric our knowledge, is the first evidence Building resilience in challenging times a Nutric donating ruthenium complex inhibits MSU-induced heatlh inflammation and healtj.
Further, complex I targets the main physiopathological mechanisms of gout Nitrix. Therefore, it is heath that Joint health strength I and Nitrif NO donors have therapeutic potential that deserves further investigation, Nitric oxide and joint health.
Gouty arthritis or gout is oxkde main cause adn joint inflammation in men VanItallie, Patients are affected by agonizing pain and swelling in the joint, which cause disability and nad impair the quality of life Roddy et al.
Anx etiology of gout is related to the Premium Fruit Gifts of serum anx acid levels due to changes in its metabolism, Nitroc as healtb production or decreased excretion, which means that its solubility is exceeded Chilappa healrh al.
The increased concentration of circulating healtj acid culminates amd deposition of Nutritional considerations for multi-stage endurance events urate crystals Ojint in the joints and in periarticular tissues. Oxiide deposition of these crystals activate components of the innate immune system and produces an local inflammatory response Dieppe ozide al.
The inflammatory anx triggered by Combating fatigue with proper nutrition acid crystals involves mechanisms such Body pump classes Nitric oxide and joint health local Weight loss strategies stress by the oxlde of NADPH oxidases Busso jount So, ; leukocyte infiltration, especially neutrophils Popa-Nita and Detoxify the body slimming pills, ; production of inflammatory mediators, such as tumor necrosis factor alpha TNF-α and interleukin IL -6 di Giovine et ooxide.
In especially, NALP3 inflammasome matures Martinon et al. This pathway is one of the most characteristic innate immune mechanisms of gout. The pharmacological treatment recommended for acute attacks of gout Nitgic to relieve Boost endurance and strength symptoms Nitrci consists of healh anti-inflammatory Nihric NSAIDsoxife or corticosteroids Baker and Ralph Schumacher, In situations znd recurrence and chronicity, drug therapy an to decrease uric acid levels using xanthine-oxidase inhibitors especially anx and Nitricc agents Baker and Ralph Schumacher, ahd Despite the Nitric oxide and joint health, its use may be accompanied oxive various side effects such as hypersensitivity reactions, renal and gastrointestinal Venom immunotherapy Seth et al.
Recently, the use of IL-1 inhibitors has proved noint be an important anx approach in gout So et oxidde. In Recovery diet for injuries sense, oxire therapeutic approaches have been jount in order jount reduce Creative problem-solving methods, control oxidf and joinf improvement of life joijt for patients with a oxidw cost.
Nitric oxide Jiint is moint key molecule Recovery diet for injuries pain modulation and its therapeutic effect in painful and inflammatory oxdie has been demonstrated in different Nitrc through the use of NO donors Nitrlc et al.
The jkint NO donors inhibit inflammatory pain behaviors induced by formalin and carrageenan by reducing the recruitment of neutrophils Staurengo-Ferrari et al. The nitric oxide donor cis -[Ru bpy 2 SO gealth NO] PF 6 has protective effect jooint Nitric oxide and joint health gastric mucosa against heakth damage caused by naproxen or ethanol Blood sugar crash after eating mice Santana et al.
Considering the evidences of the anti-inflammatory and analgesic effect of NO donors in different animal models, it is plausible the hypothesis Nitric oxide and joint health this class Body fat measurement molecules would be effective Hunger management strategies the treatment of lxide and Nitric oxide and joint health in gout.
On the other hand, there is also evidence that inhibition of inducible nitric oxide synthase iNOS diminishes gout-induced mRNA expression of inflammatory markers and inflammation Ju et al.
Further, to our knowledge, there is no study evaluating the effect of NO donors in MSU-induced gout inflammation and pain. Therefore, we reason that evaluating the effect of a NO donor in the context of gout is necessary.
In this context, this study evaluated the effect and mechanisms of ruthenium NO donor [Ru bpy 2 NO SO 3 ] PF 6 in the treatment of gout arthritis.
The experiments were always conducted at the same time of day and the animals were monitored daily for evaluation of general health status. All experiments were performed with the approval of the Ethics Committee for Animal Research of the Universidade Estadual de Londrina UEL process number The following drugs were obtained from the sources: Glibenclamide GLB and KT were obtained from Sigma Aldrich St.
Louis, MO, United States. Ruthenium NO donor [Ru bpy 2 NO SO 3 ] PF 6 was synthesized and used as previously described Silva et al. The ruthenium NO donor [Ru bpy 2 NO SO 3 ] PF 6 complex I synthesis and characterization were performed as previously described Silva et al.
Aiming to quantify ruthenium in this complex, a methodology proposed by Rowston and Ottaway was used with modification. For this, a Ru cathode lamp, a flame air-acetylene and flame atomic absorption spectrophotometer Varian, model AAFS were used.
For measurements in acetonitrile, tetrabutylammonium perchlorate 0. For measurements in aqueous medium, sodium trifluoroacetate 0. A similar complex to complex I was synthesized without NO and used as a control in the initial behavior and cell count experiments.
Monosodium urate crystals were prepared according to the method described previously Nishimura et al. Briefly, mg of monosodium urate was dissolved in ml boiling water containing 5 ml 1N NaOH, the pH was adjusted to 7.
The crystals were collected by centrifugation at 3, g for 2 min at 4°C. The crystals were evaporated and sterilized by heating at °C for 2 h and stored in a sterile environment until use.
Joint inflammation characteristic of gout was induced by intra-articular i. Control animals received an intra-articular injection of 10 μl sterile saline. The dose of MSU was determined in previous study Ruiz-Miyazawa et al.
Hypersensitivity to mechanical stimulation was tested in mice using an electronic version of the von Frey filaments, as previously reported Guerrero et al. Briefly, the test consists of evoking a tibio-tarsal flexion reflex with a hand-held force transducer electronic von Frey analgesimeter; Insight, Ribeirão Preto, SP, Brazil adapted with a non-nociceptive tip probe with area size of 4.
The investigator was trained to apply the tip perpendicularly to the central area of the plantar surface, inducing the flexion of the hind limb joints. The results were expressed as the flexion-elicited withdrawal threshold in grams.
The hypersensitivity to mechanical stimuli was quantified as the change in pressure applied by subtracting the mean of the 3 values obtained in different times after the MSU injection from the mean of the three values observed before MSU injection. The articular volume was measured with a gauge Mitutoyo, Suzano, SP, Brazil before baseline and after the intra-articular stimulus with MSU.
The values were obtained by subtracting the baseline values from the measurements obtained at each time point 1, 3, 5, 7, and 15 h after i. MSU injection. After a surgical incision, the knee joint was exposed and washed three times with 5 μL of phosphate-buffered saline PBS.
Total leukocyte counts were determined in a Neubauer chamber after dilution in Turk solution. To distinguish polymorphonuclear PMNs from mononuclear cells, differential cell counts were performed using the Fast Panoptic Kit for histological analysis Laborclin, Pinhais, PR, Brazil under a light microscope Olympus Optical Co.
The results are expressed as number of cells × 10 4 per joint. DAPI fluorescent stain was added to slides for localization of nucleus in each sample. The representative images and quantitative analysis were performed using a confocal microscope TCS SP8, Leica Microsystems, Mannheim, Germany Zarpelon et al.
The intensity of fluorescence was quantified in randomly selected fields of different groups by a blind evaluator. Result is presented as the eGFP fluorescent intensity.
The knee joint of mice was removed 15 h after MSU stimulus after euthanasia. The paraffin sections were stained with hematoxylin and eosin for blinded morphological analysis and scored by a pathologist using light microscopy. The final score was determined by summing the three parameters for each sample expressed as the mean of 5 samples accordingly to the group, and the maximum total score considered was 9.
The results are expressed as the median value variation for each group of five animals. Images were obtained at 10 and 40× magnification. These tests were adapted to a well microplate format as previously described Campanini et al.
Articular tissue samples were collected 15 h after MSU i. The homogenates were centrifuged g × 10 min × 4°Cand the supernatants were used in both assays. Diluted ABTS solution μl was added to 10 μl of sample in each well and the absorbance was measured at nm after 6 min of incubation at 25°C.
For FRAP assay, the supernatants 10 μl were mixed with the freshly prepared FRAP reagent μl and after incubation at 37°C for 30 min, the absorbance was measured at nm Multiskan GO Thermo Scientific.
The results of FRAP and ABTS assays were equated against a standard Trolox curve 0. per mg of tissue. The samples were homogenized with μl of 0. The mixture was centrifuged 15 min × 1, g × 4°C and the supernatant was added to μl of 0.
After 5 min, the absorbance was measured at nm Multiskan GO, Thermo Scientific. The results are obtained were compared to a standard curve of GSH Borghi et al. The knee joint samples were collected 15 h after MSU i.
The levels of IL-1β, TNF-α, IL-6, and IL were determined by enzyme-linked immunosorbent assay ELISA using commercial kits eBioscience, San Diego, CA, United States. Absorbance was measured at nm Multiskan GO, Thermo Scientific and the results are expressed as picograms of cytokines per mg of tissue.
Louis, MO, United States containing protease and phosphatase inhibitors Cell Signaling Technology, Beverly, MA, United States.
The lysates were then homogenized and centrifuged 0. The protein concentrations of the lysate were determined using a BCA Protein Assay kit Pierce, Rockford, IL, United Statesand μg of protein was loaded for each lane. The primary antibodies used to Western blot were IL-1β ; Cell Signaling Technology, Beverly, MA, United States and β-Actin ; Santa Cruz Biotechnology.
After washing in TBS with Tween 20, the membrane was incubated with a HRP-conjugated secondary antibody ; Jackson Immuno Research, West Grove, PA, United States for 2 h at room temperature. Protein was visualized by chemiluminescence with Luminata TM Forte Western HRP Substrate Merck Millipore Corporation, Darmstadt, Alemanha.
The molecular protein mass was confirmed by PageRuler TM Prestained Protein Ladder Thermo Scientific, Rockford, IL, United States. The membranes were reprobed with antibody against β-Actin to be used as loading control. Densitometric data were measured using Scientific Imaging Systems Image Lab 3.
Mice were euthanized 15 h after the i. injection of MSU, the knee joint samples were collected, homogenized in μl of Trizol reagent and centrifuged 12, rcf, 15 min, 4°C. Total RNA was extracted using the SV Total RNA Isolation System Promega Verri et al.
qPCR was performed in a LightCycler Nano Instrument Roche, Mississauga, ON, United States sequence detection system using the Platinum SYBR Green qPCR SuperMix UDG Invitrogen, United States.
The mRNA level of glyceraldehyde 3-phosphate dehydrogenase GAPDH was used as an internal control.
: Nitric oxide and joint health| Introduction | Nitric oxide synthesis and its regulation by rabbit synoviocytes. J Rheumatol ; 21 : —8. Sakurai H, Kohsaka H, Liu M et al. Nitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritis. J Clin Invest ; 96 : — Grabowski PS, Wright PK, van 't Hof RJ, Helfrich MH, Oshima H, Ralston SH. Immunolocalisation of inducible nitric oxide synthase in the synovium and cartilage in rheumatoid arthritis and osteoarthritis. Br J Rheumatol ; 36 : —5. Firestein GS, Yeo M, Zvaifler NJ. Apoptosis in rheumatoid arthritis synovium. J Clin Invest ; 96 : —8. Nakajima T, Aono H, Hasunuma T et al. Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes. Arthritis Rheum ; 38 : — Sioud M, Mellbye O, Forre O. Clin Exp Rheumatol ; 16 : — Brune B, Gotz C, Messmer UK, Sandau K, Hirvonen MR, Lapetina EG. J Biol Chem ; : —8. Albina JE, Cui S, Mateo RB, Reichner JS. J Immunol ; : —5. Blanco FJ, Ochs RL, Schwarz H, Lotz M. Chondrocyte apoptosis induced by nitric oxide. Am J Pathol ; : 75 — Turpaev KT, Amchenkova AM, Narovlyansky AN. Biochem Mol Biol Int ; 41 : — Boudreau N, Sympson CJ, Werb Z, Bissell MJ. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix mammary cells in tissue culture and in vivo. Science ; : —2. Aupperle KR, Boyle DL, Hendrix M et al. Regulation of synoviocyte proliferation, apoptosis, and invasion by the p53 tumor suppressor gene. Am J Pathol ; : —8. Kobayashi T, Okamoto K, Kobata T, Hasunuma T, Sumida T, Nishioka K. Arthritis Rheum ; 42 : — Biochem Biophys Res Commun ; : —8. Murrell GA, Jang D, Williams RJ. Nitric oxide activates metalloprotease enzymes in articular cartilage. Biochem Biophys Res Commun ; : 15 — Wei XQ, Charles IG, Smith A et al. Altered immune response in mice lacking inducible nitric oxide synthase. Nature ; : — Ralston SH, Grabowski PS. Mechanisms of cytokine induced bone resorption: Role of nitric oxide, cyclic guanosine monophosphate, and prostaglandins. Bone ; 19 : 29 — Firestein GS. Novel therapeutic strategies involving animals, arthritis, and apoptosis. Curr Opin Rheumatol ; 10 : — Morita I, Matsuno H, Sakai K et al. Int J Tissue React ; 20 : 37 — Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Advertisement intended for healthcare professionals. Navbar Search Filter Rheumatology This issue British Society for Rheumatology Journals Rheumatology Books Journals Oxford Academic Mobile Enter search term Search. Issues More Content Advance Articles Editor's Choice Collections Podcasts Videos Supplements Guidelines InSight Papers BSR Registers Papers Virtual Roundtables Submit Author Guidelines Submission Site Open Access Options Self-Archiving Policy Why Submit Purchase Alerts About About Rheumatology About the British Society for Rheumatology Editorial Board Advertising and Corporate Services Journals Career Network Dispatch Dates Terms and Conditions Journals on Oxford Academic Books on Oxford Academic. British Society for Rheumatology Journals. Issues More Content Advance Articles Editor's Choice Collections Podcasts Videos Supplements Guidelines InSight Papers BSR Registers Papers Virtual Roundtables Submit Author Guidelines Submission Site Open Access Options Self-Archiving Policy Why Submit Purchase Alerts About About Rheumatology About the British Society for Rheumatology Editorial Board Advertising and Corporate Services Journals Career Network Dispatch Dates Terms and Conditions Close Navbar Search Filter Rheumatology This issue British Society for Rheumatology Journals Rheumatology Books Journals Oxford Academic Enter search term Search. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Journal Article. Nitric oxide is a mediator of apoptosis in the rheumatoid joint. van't Hof , R. van't Hof. Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen AB25 2ZD, UK. Oxford Academic. Google Scholar. Revision received:. PDF Split View Views. Cite Cite R. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions. Close Navbar Search Filter Rheumatology This issue British Society for Rheumatology Journals Rheumatology Books Journals Oxford Academic Enter search term Search. Abstract Objective. Rheumatoid arthritis , Cytokines , Nitric oxide , Apoptosis , Cartilage , Synovium. Open in new tab Download slide. Ann Rheum Dis. Eur J Pharmacol. Arthritis Rheum. J Exp Med. Br J Pharmacol. Biochem Biophys Res Commun. J Immunol. Br J Rheum. J Rheumatol. J Clin Invest. Br J Rheumatol. Clin Exp Rheumatol. J Biol Chem. Am J Pathol. Biochem Mol Biol Int. Curr Opin Rheumatol. Int J Tissue React. Issue Section:. Download all slides. Comments 0. Add comment Close comment form modal. I agree to the terms and conditions. You must accept the terms and conditions. NLRP3 inflammasome allows the activation of pro- caspase-1 into active caspase-1 that cleaves pro-IL-1β into IL-1β, which undergoes secretion. IL-1β in turn contributes to inducing inflammation and pain as well as further activation of NF-κB to induce the expression of inflammasome components NLRP3, ASC, pro-caspase-1, and pro-IL-1β Zhang et al. This result agrees with the effect of complex I on MSU-induced production of TNF-α and IL Not only in gout arthritis, but in most inflammatory disease, NF-κB regulates the transcription of varied inflammatory molecules Pahl, ; Tak and Firestein, Inhibiting NF-κB activation is also a mechanism of action of glucocorticoids Verri et al. In this sense, drugs that target NF-κB without the side effects of glucocorticoids have a great potential to be useful in varied human inflammatory diseases. IL-1β is a key cytokine in gout inflammation considering the importance of NLRP3 Mitroulis et al. We observed that MSU-induced an increase of pro-IL-1β expression in vivo , which was diminished by complex I. This result agrees with the complex I inhibition of MSU-induced NF-κB activation. Inhibition of the NF-κB signaling pathway appears to be at least one of the mechanisms involved in modulating NO on inflammation, since treatment with NO donors decreases the expression of adhesion molecules by inhibiting activation of NF-κB in human saphenous vein De Caterina et al. Complex I also inhibited MSU-induced IL-1β production and pro-il-1β and nlrp3 mRNA expression in the knee joint. Further, we used an in vitro assay designed to evaluate MSU-induced NLRP3 inflammasome activation Martinon et al. Bone marrow derived macrophages BMDM received as signal 1 lipopolysaccharide of Gram-negative bacteria LPS. BMDM also received signal 2 MSU , which induced the release of IL-1β in the culture media. Complex I significantly inhibited MSU-induced release of IL-1β in the culture media indicating that the NO donor effect involves inhibition of inflammasome activation. This is an important mechanism considering the effectiveness of anti-IL-1 therapies for the treatment of human gout arthritis So et al. The importance of TRPV1 activation has been demonstrated in MSU-induced acute gout attacks Ramonda et al. The immunoreactivity of the TRPV1 receptor in the joint tissue of animals stimulated with MSU crystals is increased Hoffmeister et al. Treatment with selective TRPV1 antagonists as well as desensitization or defunctionalization of afferent fibers sensitive to capsaicin inhibits MSU-induced pain and edema in rats Hoffmeister et al. Plasma extravasation, leukocyte infiltration and articular fluid IL-1β production induced by MSU are also decreased by the TRPV1 antagonist SB Hoffmeister et al. Therefore, considering the importance of TRPV1 activation in the pathophysiology of gout arthritis, we evaluated the effect of complex I in capsaicin-induced calcium influx in DRG neurons of mice that were stimulated with MSU. Complex I inhibited the TRPV1 activation-induced calcium influx of capsaicin responsive neurons harvested from mice with gout arthritis. In vitro studies comparing NO release capacity demonstrated that Complex I is capable of releasing NO after reacting with thiols and presents superior physico-chemical properties and stability compared to other metal complexes Silva et al. In addition to NO, the thiol reaction with metallonitrosyl complexes, such as Complex I, can generate HNO nitroxyl Silva Sousa et al. Nitroxyl donors have also analgesic, anti-inflammatory and microbicide actions Zarpelon et al. The release of NO by Complex I is mediated by a reaction involving thiols such as cysteine and glutathione Silva et al. Since the development of novel NO donor metallic complexes has been the subject of recent studies, the literature on the pharmacokinetics of the Complex I, for example, has not yet been reported. Therefore, ruthenium NO complexes represent a topic that deserves further investigation. To our knowledge, this is the first demonstration that treatment with a ruthenium complex NO donor inhibits MSU-induced inflammation and pain, thus, suggesting this NO donation using ruthenium complex as a promising therapeutic approach in the management of gout inflammation. The mechanism of action of complex I also depends on the inhibition of MSU-induced inflammasome activation and reducing neuronal activation. Therefore, the present data suggest a promising therapeutic property of complex I, given it targets the main pathophysiological mechanisms of gout arthritis. The multitarget mechanism of action with direct analgesic actions present data and safe profile at the present dose Silva et al. AR, DL-B, MB, VF, CS-V, SB-G, TZ, LS-F, SB, TC, AB and FG contributed to the data collection and analysis. AR, LL, RC, and WV contributed to the literature database search, data analysis, and writing of the manuscript. WV supervised the study. All authors read and approved the final version of the manuscript. AR received CAPES and CNPq Post-Doc fellowships. SMB received a CNPq Postdoctoral fellowship. The authors thank the support of CMLP-UEL Central Multiusuário de Laboratórios de Pesquisa — Universidade Estadual de Londrina. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Amaral, F. Transmembrane TNF-α is sufficient for articular inflammation and hypernociception in a mouse model of gout. doi: PubMed Abstract CrossRef Full Text Google Scholar. Anrather, J. NF-kappaB regulates phagocytic NADPH oxidase by inducing the expression of gp91phox. Baker, J. Update on gout and hyperuricemia. Bauernfeind, F. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. Blaser, H. TNF and ROS Crosstalk in Inflammation. Trends Cell Biol. Borghi, S. Busso, N. The mechanisms of inflammation in gout and pseudogout CPP-induced arthritis. Reumatismo 63, — Mechanisms of inflammation in gout. Arthritis Res. Campanini, M. Efficacy of topical formulations containing Pimenta pseudocaryophyllus extract against UVB-induced oxidative stress and inflammation in hairless mice. B Biol. Campochiaro, C. Allopurinol-induced severe cutaneous adverse reactions. Cavalcanti, N. Cytokine profile in gout: inflammation Driven by IL-6 and IL? Chen, Y. Spontaneous resolution of acute gouty arthritis is associated with rapid induction of the anti-inflammatory factors TGF 1, IL and soluble TNF receptors and the intracellular cytokine negative regulators CIS and SOCS3. Chilappa, C. Gout and hyperuricemia. Google Scholar. Chiu, I. Bacteria activate sensory neurons that modulate pain and inflammation. Nature , 52— Choe, J. Radiographic bone damage in chronic gout is negatively associated with the inflammatory cytokines soluble interleukin 6 receptor and osteoprotegerin. Cunha, T. Cury, Y. Pain and analgesia: the dual effect of nitric oxide in the nociceptive system. Nitric Oxide 25, — De Caterina, R. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. Del Carlo, M. Nitric oxide-mediated chondrocyte cell death requires the generation of additional reactive oxygen species. Arthritis Rheum. Di Cesare Mannelli, L. Therapeutic effects of the superoxide dismutase mimetic compound me 2 DO2A on experimental articular pain in rats. Mediators Inflamm. di Giovine, F. Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells. Cytokine mRNA and protein kinetics, and cellular distribution. Dieppe, P. Inflammatory responses to intradermal crystals in healthy volunteers and patients with rheumatic diseases. Dumusc, A. Interleukin-1 as a therapeutic target in gout. Engel, B. Treatment options for gout. Failli, P. A novel manganese complex effective as superoxide anion scavenger and therapeutic agent against cell and tissue oxidative injury. Faust, N. Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. Blood 96, — PubMed Abstract Google Scholar. Guerne, P. Inflammatory microcrystals stimulate interleukin-6 production and secretion by human monocytes and synoviocytes. Guerrero, A. Hypernociception elicited by tibio-tarsal joint flexion in mice: a novel experimental arthritis model for pharmacological screening. Hitchon, C. The synovium in rheumatoid arthritis. Open Rheumatol. Hoffmeister, C. Participation of the TRPV1 receptor in the development of acute gout attacks. Rheumatology 53, — Role of TRPV1 in nociception and edema induced by monosodium urate crystals in rats. Pain , — Hsu, Y. Nitric oxide donors rescue diabetic nephropathy through oxidative-stress-and nitrosative-stress-mediated Wnt signaling pathways. Diabetes Investig. Ju, T. Inhibition of inducible nitric oxide synthase attenuates monosodium urate-induced inflammation in mice. Korean J. Kuo, C. Global epidemiology of gout: prevalence, incidence and risk factors. Lee, H. Inhibition of cyclooxygenase 2 expression by diallyl sulfide on joint inflammation induced by urate crystal and IL-1β. Lee, J. Interaction of IL-6 and TNF-α contributes to endothelial dysfunction in type 2 diabetic mouse hearts. PLoS One e Lee, Y. The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief. CrossRef Full Text Google Scholar. Li, B. IL modulates DSS-induced colitis through a macrophage—ROS—NO axis. Mucosal Immunol. Lin, C. Free Radic. Liu-Bryan, R. Intracellular innate immunity in gouty arthritis: role of NALP3 inflammasome. Cell Biol. Longhi-Balbinot, D. Martinon, F. Update on biology: uric acid and the activation of immune and inflammatory cells. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature , — Mitroulis, I. Neutrophils, IL-1β, and gout: is there a link? Moilanen, L. Urate crystal induced inflammation and joint pain are reduced in transient receptor potential ankyrin 1 deficient mice — potential role for transient receptor potential ankyrin 1 in gout. Murakami, Y. Antiinflammatory effect of retrovirally transfected interleukin on monosodium urate monohydrate crystal-induced acute inflammation in murine air pouches. Ng, T. Regulation of adaptive immunity; the role of interleukin Nishimura, A. Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin Orlowski, G. Multiple cathepsins promote Pro—IL-1β Synthesis and NLRP3-mediated IL-1β activation. Pahl, H. Oncogene 18, — Peng, Y. Pycnogenol attenuates the inflammatory and nitrosative stress on joint inflammation induced by urate crystals. Popa-Nita, O. Crystal-induced neutrophil activation. Pouliot, M. Monosodium urate microcrystals induce cyclooxygenase-2 in human monocytes. Blood 91, — Prado, W. Dual effect of local application of nitric oxide donors in a model of incision pain in rats. Ramonda, R. Pain and microcrystalline arthritis. Reumatismo Regan, E. Extracellular superoxide dismutase and oxidant damage in osteoarthritis. Rock, K. Uric acid as a danger signal in gout and its comorbidities. Roddy, E. Is gout associated with reduced quality of life? A case-control study. Rheumatology 46, — Rowston, W. The determination of ruthenium by atomic absorption spectrophotometry. Ruiz-Miyazawa, K. Quercetin inhibits gout arthritis in mice: induction of an opioid-dependent regulation of inflammasome. Inflammopharmacology 25, — Ruiz-Romero, C. Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance. Proteomics 8, — Sachs, D. Santana, A. The nitric oxide donor cis-[Ru bpy 2 SO3 NO] PF6 increases gastric mucosa protection in mice? Nitric Oxide 45, 35— Seth, R. Silva, F. Silva, J. Silva Sousa, E. Thiol-activated HNO release from a ruthenium antiangiogenesis complex and HIF-1α inhibition for cancer therapy. ACS Chem. Singh, J. BMC Med. PubMed Abstract CrossRef Full Text. Gout is associated with more comorbidities, poorer health-related quality of life and higher healthcare utilisation in US veterans. So, A. A pilot study of IL-1 inhibition by anakinra in acute gout. Inflammation in gout: mechanisms and therapeutic targets. Sousa, A. The dual effect of a nitric oxide donor in nociception. Brain Res. Staurengo-Ferrari, L. Schmiedebergs Arch. Tak, P. NF-κB: a key role in inflammatory diseases. Trevisan, G. TRPA1 receptor stimulation by hydrogen peroxide is critical to trigger hyperalgesia and inflammation in a model of acute gout. van Echteld, I. VanItallie, T. Gout: epitome of painful arthritis. Metabolism 59, S32—S Verri, W. Hypernociceptive role of cytokines and chemokines: targets for analgesic drug developement? IL mediates antigen-induced cutaneous and articular hypernociception in mice. Waldow, T. Nitric oxide donor-induced persistent inhibition of cell adhesion protein expression and NFκB activation in endothelial cells. Nitric Oxide 15, — Yokose, K. TNF- α potentiates uric acid-induced interleukin-1 β IL-1 β secretion in human neutrophils. Yu, X. Calcium influx through hyperpolarization-activated cation channels I h channels contributes to activity-evoked neuronal secretion. Zamudio-Cuevas, Y. Molecular basis of oxidative stress in gouty arthropathy. Monosodium urate crystals induce oxidative stress in human synoviocytes. Zarpelon, A. Spinal cord oligodendrocyte-derived alarmin IL mediates neuropathic pain. FASEB J. Neuropharmacology 71, 1—9. Zhang, H. The inflammasome as a target for pain therapy. Zheng, S. Role of the NLRP3 inflammasome in the transient release of IL-1β induced by monosodium urate crystals in human fibroblast-like synoviocytes. Zimmermann, M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16, — Citation: Rossaneis AC, Longhi-Balbinot DT, Bertozzi MM, Fattori V, Segato-Vendrameto CZ, Badaro-Garcia S, Zaninelli TH, Staurengo-Ferrari L, Borghi SM, Carvalho TT, Bussmann AJC, Gouveia FS Jr, Lopes LGF, Casagrande R and Verri WA Jr [Ru bpy 2 NO SO 3 ] PF 6 , a Nitric Oxide Donating Ruthenium Complex, Reduces Gout Arthritis in Mice. Received: 10 August ; Accepted: 22 February ; Published: 12 March Copyright © Rossaneis, Longhi-Balbinot, Bertozzi, Fattori, Segato-Vendrameto, Badaro-Garcia, Zaninelli, Staurengo-Ferrari, Borghi, Carvalho, Bussmann, Gouveia, Lopes, Casagrande and Verri. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Rossaneis, anacrossaneis gmail. com Waldiceu A. Verri Jr. br ; waldiceujr yahoo. br orcid. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Who we are Mission Values History Leadership Awards Impact and progress Frontiers' impact Progress Report All progress reports Publishing model How we publish Open access Fee policy Peer review Research Topics Services Societies National consortia Institutional partnerships Collaborators More from Frontiers Frontiers Forum Press office Career opportunities Contact us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. ORIGINAL RESEARCH article Front. Experimental Pharmacology and Drug Discovery. Ana C. Longhi-Balbinot 1 Mariana M. Bertozzi 1 Victor Fattori 1 Carina Z. Segato-Vendrameto 1 Stephanie Badaro-Garcia 1 Tiago H. Zaninelli 1 Larissa Staurengo-Ferrari 1 Sergio M. Borghi 1 Thacyana T. Carvalho 1 Allan J. Bussmann 1 Florêncio S. Gouveia Jr. Introduction Gouty arthritis or gout is the main cause of joint inflammation in men VanItallie, Drugs The following drugs were obtained from the sources: Glibenclamide GLB and KT were obtained from Sigma Aldrich St. Ruthenium NO Donor [Ru bpy 2 NO SO 3 ] PF 6 Complex I Synthesis The ruthenium NO donor [Ru bpy 2 NO SO 3 ] PF 6 complex I synthesis and characterization were performed as previously described Silva et al. MSU Crystal Preparation Monosodium urate crystals were prepared according to the method described previously Nishimura et al. Model of Gout Joint inflammation characteristic of gout was induced by intra-articular i. Electronic Pressure Meter Test of Mechanical Hypersensitivity Hypersensitivity to mechanical stimulation was tested in mice using an electronic version of the von Frey filaments, as previously reported Guerrero et al. Edema Assessment The articular volume was measured with a gauge Mitutoyo, Suzano, SP, Brazil before baseline and after the intra-articular stimulus with MSU. Leukocyte Recruitment After a surgical incision, the knee joint was exposed and washed three times with 5 μL of phosphate-buffered saline PBS. Histological Analysis The knee joint of mice was removed 15 h after MSU stimulus after euthanasia. GSH Levels Measurement Articular tissue samples were collected 15 h after MSU i. Cytokines Measurement The knee joint samples were collected 15 h after MSU i. NF-κB Activation The knee joint samples were collected 15 h after MSU i. |
| Nitric Oxide Information | Article CAS PubMed Google Scholar. Alving, K. Increased amount of nitric oxide in exhaled air of asthmatics. CAS PubMed Google Scholar. Högman, M. et al. Extended NO analysis applied to patients with COPD, allergic asthma and allergic rhinitis. Article PubMed Google Scholar. Damiani, G. Patients with psoriatic arthritis have higher levels of F E NO than those with only psoriasis, which may reflect a higher prevalence of a subclinical respiratory involvement. Tiev, K. Diagnostic value of exhaled nitric oxide to detect interstitial lung disease in systemic sclerosis. Sarcoidosis Vasc. Diffuse Lung Dis. Ludviksdottir, D. Malar rash is a predictor of subclinical airway inflammation in patients with systemic lupus erythematosus: a pilot study. Utilising exhaled nitric oxide information to enhance diagnosis and therapy of respiratory disease - current evidence for clinical practice and proposals to improve the methodology. Expert Rev. Farrell, A. Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Article CAS PubMed PubMed Central Google Scholar. Ali, A. Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients. Nitric oxide is a mediator of apoptosis in the rheumatoid joint. Rheumatology Oxford 39 9 , — Article Google Scholar. Chow, Y. The role of inflammation in the pathogenesis of osteoarthritis. Catrina, A. Lungs, joints and immunity against citrullinated proteins in rheumatoid arthritis. Smolen, J. Rheumatoid arthritis. Demoruelle, M. Brief report: airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: Early injury or initiating site of autoimmunity?. Arthritis Rheum. Deane, K. Rheumatoid arthritis: Pathogenesis, prediction and prevention—An emerging paradigm shift. Arthritis Rheumatol. Thornadtsson, A. Altered levels of exhaled nitric oxide in rheumatoid arthritis. Nitric Oxide 76 , 1—5 Aletaha, D. Extended NO analysis in a healthy subgroup of a random sample from a Swedish population. Imaging 29 1 , 18—23 Ekdahl, C. Assessing disability in patients with rheumatoid arthritis. Use of a Swedish version of the Stanford Health Assessment Questionnaire. Prevoo, M. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. American Thoracic, S. Care Med. Horvath, I. A European Respiratory Society technical standard: Exhaled biomarkers in lung disease. J 49 4 , 17E Hedenström, H. Reference values for lung function tests in female. Regression equations with smoking variables. PubMed Google Scholar. Reference values for pulmonary function test in men: Regression equations which include tobacco smoking variables. Upsala J. Sugiyama, D. Impact of smoking as a risk factor for developing rheumatoid arthritis: A meta-analysis of observational studies. Stolt, P. Silica exposure among male current smokers is associated with a high risk of developing ACPA-positive rheumatoid arthritis. Too, C. Occupational exposure to textile dust increases the risk of rheumatoid arthritis: Results from a Malaysian population-based case-control study. Increased nitric oxide elimination from the airways after smoking cessation. Malinovschi, A. Effect of smoking on exhaled nitric oxide and flow-independent nitric oxide exchange parameters. Taylor, B. The impact of tetrahydrobiopterin administration on endothelial function before and after smoking cessation in chronic smokers. Hypertens Res. Karvonen, T. Onset of action of inhaled glucocorticoids on bronchial and alveolar nitric oxide output. Breath Res. Silkoff, P. Airway nitric oxide diffusion in asthma. Role in pulmonary function and bronchial responsiveness. Bordy, R. Methotrexate did not improve endothelial function in rheumatoid arthritis: A study in rats with adjuvant-induced arthritis. Nettelbladt, E. Amino-acid content of serum in rheumatoid arthritis. Huang, L. Arginase levels are increased in patients with rheumatoid arthritis. Kaohsiung J. Chandrasekharan, U. Elevated levels of plasma symmetric dimethylarginine and increased arginase activity as potential indicators of cardiovascular comorbidity in rheumatoid arthritis. Arthritis Res. Article PubMed PubMed Central Google Scholar. Vitecek, J. Arginine-based inhibitors of nitric oxide synthase: therapeutic potential and challenges. Gaston, B. The biology of nitrogen oxides in the airways. Ricciardolo, F. Reactive nitrogen species in the respiratory tract. Download references. The authors wish to thank all of the patients that participated in the study, especially those that came back for the follow-up. Special thanks to L. The authors also wish to thank Robin Quell for proofreading and editing this manuscript. The NO analyser was paid for by funds from the Gävle Cancer Foundation. Department of Medical Science, Rheumatology, Uppsala University, , Uppsala, Sweden. Department of Medical Science, Clinical Chemistry, Uppsala University, , Uppsala, Sweden. Department of Immunology, Genetics and Pathology, Uppsala University, , Uppsala, Sweden. Department of Medical Science, Respiratory, Allergy and Sleep Research, Uppsala University, , Uppsala, Sweden. Department of Rheumatology, Region Gävleborg, Box , , Gävle, Sweden. You can also search for this author in PubMed Google Scholar. and M. designed the study, T. and A. recruited the patients, J. performed the chemical and immunological analyses. were responsible for the acquisition of the data and statistically analysing it. All authors were responsible for the interpretation of the data and for drafting, revising and approving the final submitted manuscript. Correspondence to Tomas Weitoft. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions. Weitoft, T. Exhaled nitric oxide in early rheumatoid arthritis and effects of methotrexate treatment. Sci Rep 12 , Download citation. Received : 06 September Accepted : 30 March Published : 20 April Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Skip to main content Thank you for visiting nature. nature scientific reports articles article. Download PDF. Subjects Inflammation Rheumatic diseases. Abstract Patients with established rheumatoid arthritis RA and disease modifying treatments have lower nitric oxide NO levels in the alveolar compartment C A NO and in the airway wall C aw NO , but also higher diffusion capacities for NO in the airways D aw NO compared to matched controls. Introduction Nitric oxide NO is an endogenous biatomic gaseous molecule involved in several important biological processes in the human body, with a key position in the inflammatory reaction by promoting vascular dilatation and permeability. Data collection The patients were evaluated clinically by their treating rheumatologist TW, ALi. Lung function Pre-bronchodilator spirometry lung function testing was performed using Welch Allyn. Blood analysis Blood samples were collected for analysis of inflammatory markers, such as Erythrocyte Sedimentation Rate ESR and serum C-Reactive Protein s-CRP. Statistical analyses All statistical analyses were performed using SPSS, v. Ethical approval The study was performed in accordance with Helsinki Declaration. Results A total of 51 patients were recruited to the study. Figure 1. Flowchart of included and excluded patients in protocol A and B of the study. Full size image. Table 1 Characteristics of patients and control subjects in Protocol A. Data given in median lower and upper quartiles. Full size table. Table 2 Characteristics of smoking and non-smoking patients in Protocol B. Discussion In patients with recent onset ACPA positive RA the NO content in the airway wall was lower, NO diffusion capacity over the airway wall was higher and the alveolar NO was lower when compared to matched healthy controls. Conclusion Our studies on the changes in the NO dynamics of patients with established and recent onset RA are the first to describe the higher diffusion capacity and lower levels in the airway wall and alveoli compared to matched control subjects. Data availability Data are available upon reasonable request by contacting the corresponding author. References Boucher, J. Article CAS PubMed Google Scholar Alving, K. CAS PubMed Google Scholar Högman, M. Article PubMed Google Scholar Damiani, G. Article PubMed Google Scholar Tiev, K. CAS PubMed Google Scholar Ludviksdottir, D. Article CAS PubMed Google Scholar Damiani, G. Article PubMed Google Scholar Högman, M. Article PubMed Google Scholar Farrell, A. Article CAS PubMed PubMed Central Google Scholar Ali, A. Article Google Scholar Chow, Y. Article Google Scholar Catrina, A. Article CAS PubMed Google Scholar Smolen, J. Article PubMed Google Scholar Demoruelle, M. Article CAS PubMed Google Scholar Deane, K. Article PubMed Google Scholar Thornadtsson, A. Article CAS PubMed Google Scholar Aletaha, D. Article PubMed Google Scholar Ekdahl, C. Article CAS PubMed Google Scholar Prevoo, M. K Nishida, T Doi, H Inoue, The role of nitric oxide in arthritic joints: a therapeutic target? Nitric oxide NO is produced by many cell types in the joint, and its expression is delicately regulated. Depending on its concentration and cellular origin, NO appears to have both pro- and anti-inflammatory potential in the joint. Constitutively expressed nitric oxide synthase NOS produces small amounts of NO, which is essential for normal physiological homeostasis. However, inflammatory stimuli such as endotoxins, cytokines, and growth factors promote inducible NOS iNOS expression, initially as an anti-inflammatory response, and catalyse a high output of NO. Excessive NO can amplify inflammatory pathways and contribute to the development and maintenance of arthritis. Consequently, proper regulation of NO synthesis can lead to a novel therapeutic approach for inflammatory joint diseases. Further careful study will be necessary to develop new drugs to regulate the NO pathway and to determine the dosage, timing of administration, and duration of treatment in order to avoid both undesirable immunostimulatory effects and immunosuppressive effects. Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:. Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account. Choose this option to get remote access when outside your institution. Enter your library card number to sign in. If you cannot sign in, please contact your librarian. Many societies offer single sign-on between the society website and Oxford Academic. If you do not have a society account or have forgotten your username or password, please contact your society. Some societies use Oxford Academic personal accounts to provide access to their members. See below. A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions. Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian. For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more. To purchase short-term access, please sign in to your personal account above. Don't already have a personal account? Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Advertisement intended for healthcare professionals. Navbar Search Filter Modern Rheumatology This issue Clinical Medicine Medicine and Health Rheumatology Books Journals Oxford Academic Mobile Enter search term Search. Issues Advance Articles Submit Author Guidelines Submission Site Open Access Options Self-Archive Policy Reasons to publish Purchase Alerts About About Modern Rheumatology About the Japanese College of Rheumatology Editorial Board Advertising and Corporate Services Journals on Oxford Academic Books on Oxford Academic. Issues Advance Articles Submit Author Guidelines Submission Site Open Access Options Self-Archive Policy Reasons to publish Purchase Alerts About About Modern Rheumatology About the Japanese College of Rheumatology Editorial Board Advertising and Corporate Services Close Navbar Search Filter Modern Rheumatology This issue Clinical Medicine Medicine and Health Rheumatology Books Journals Oxford Academic Enter search term Search. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Journal Article. The role of nitric oxide in arthritic joints: a therapeutic target? K Nishida , K Nishida. Department of Orthopaedic Surgery, Faculty of Medicine, Okayama University Medical School. Correspondence to: K. Nishida, Department of Orthopaedic Surgery, Faculty of Medicine, Okayama University Medical School, Shikata-cho, Okayama , Japan Tel. Oxford Academic. Google Scholar. T Doi. H Inoue. Cite Cite K Nishida, T Doi, H Inoue, The role of nitric oxide in arthritic joints: a therapeutic target? Select Format Select format. ris Mendeley, Papers, Zotero. |
| Exhaled nitric oxide in early rheumatoid arthritis and effects of methotrexate treatment | Notric size image. Prevoo, M. Control animals received an intra-articular injection of 10 μl sterile saline. Multicenter Myocardial Ischemia Research Group. PubMed Central CAS PubMed Google Scholar. |
| Search articles by author | However, joints Nitrif affected healtth osteoarthritis may Boost endurance and strength all of Boost endurance and strength Nktric signs of inflammation [ 21 ]. In health the Diabetes self-care advice synthesis Body composition for athletes arginine is sufficient, but with increased oxive requirements dietary supplementation is necessary; healt Boost endurance and strength arginine is classified as a semi-essential amino acid. Holt PG, Oliver J, Bilyk N, McMenamim C, McMenamim PG, Kraal G, Thepen T Downregulation of the antigen presenting cell function s of pulmonary dendritic cells in vivo by resident alveolar macrophages. Cut-off levels for anti-CCP2 IgG and IgA were 7 arbitrary units. NO availability has long been used to define endothelial function and a reduction in NO bioavailability is generally classed as 'endothelial dysfunction' although in practice, alterations in other mediators may also be involved in this state. |
| The Role of Nitric Oxide in Managing Joint Pain and Arthritis | Google Scholar Husain S, Andrews NP, Mulcahy D, Panza JA, Quyyumi AA: Aspirin improves endothelial dysfunction in atherosclerosis. Article CAS PubMed Google Scholar van't Hof RJ, Armour KJ, Smith LM, Armour KE, Wei XQ, Liew FY, Ralston SH: Requirement of the inducible nitric oxide synthase pathway for IL induced osteoclastic bone resorption. Control levels of apoptosis were TNF-α also primes human neutrophils in a manner that these leukocytes start to respond to previously inactive concentrations of MSU as observed by IL-1β secretion Yokose et al. Inflamm Res — Regulation of adaptive immunity; the role of interleukin |
die Lustige Frage
Diese Mitteilung unvergleichlich, ist))), mir ist es interessant:)