scholarly journals The Effects of Cobalt Protoporphyrin IX and Tricarbonyldichlororuthenium (II) Dimer Treatments and Its Interaction with Nitric Oxide in the Locus Coeruleus of Mice with Peripheral Inflammation

2019 ◽  
Vol 20 (9) ◽  
pp. 2211 ◽  
Author(s):  
Patricia Moreno ◽  
Rafael Alves Cazuza ◽  
Joyce Mendes-Gomes ◽  
Andrés Felipe Díaz ◽  
Sara Polo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Locus Coeruleus ◽  
Inflammatory Pain ◽  
Protoporphyrin Ix ◽  
Heme Oxygenase 1 ◽  
Peripheral Inflammation ◽  
Inflammatory Reactions ◽  
Cobalt Protoporphyrin ◽  
Cobalt Protoporphyrin Ix

Heme oxygenase 1 (HO-1) and carbon monoxide were shown to normalize oxidative stress and inflammatory reactions induced by neuropathic pain in the central nervous system, but their effects in the locus coeruleus (LC) of animals with peripheral inflammation and their interaction with nitric oxide are unknown. In wild-type (WT) and knockout mice for neuronal (NOS1-KO) or inducible (NOS2-KO) nitric oxide synthases with inflammatory pain induced by complete Freund’s adjuvant (CFA), we assessed: (1) antinociceptive actions of cobalt protoporphyrin IX (CoPP), an HO-1 inducer; (2) effects of CoPP and tricarbonyldichlororuthenium(II) dimer (CORM-2), a carbon monoxide-liberating compound, on the expression of HO-1, NOS1, NOS2, CD11b/c, GFAP, and mitogen-activated protein kinases (MAPK) in the LC. CoPP reduced inflammatory pain in different time-dependent manners in WT and KO mice. Peripheral inflammation activated astroglia in the LC of all genotypes and increased the levels of NOS1 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK 1/2) in WT mice. CoPP and CORM-2 enhanced HO-1 and inhibited astroglial activation in all genotypes. Both treatments blocked NOS1 overexpression, and CoPP normalized ERK 1/2 activation. This study reveals an interaction between HO-1 and NOS1/NOS2 during peripheral inflammation and shows that CoPP and CORM-2 improved HO-1 expression and modulated the inflammatory and/or plasticity changes caused by peripheral inflammation in the LC.

scholarly journals The Antinociceptive, Antioxidant and Anti-Inflammatory Effects of 5-Fluoro-2-Oxindole during Inflammatory Pain

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1249
Author(s):  
Alejandro Redondo ◽  
Gabriela Riego ◽  
Olga Pol
Keyword(s):  
Inflammatory Pain ◽  
Inflammatory Responses ◽  
Protoporphyrin Ix ◽  
Mitogen Activated Protein Kinase ◽  
Oxidative Stress Marker ◽  
Heme Oxygenase 1 ◽  
Peripheral Inflammation ◽  
Dependent Manner ◽  
Protein Levels ◽  
Antinociceptive Effects

Recent studies demonstrate that 5-fluoro-2-oxindole inhibits neuropathic pain but the antinociceptive actions of this drug and its effects on the plasticity, oxidative and inflammatory changes induced by peripheral inflammation as well as on the effects and expression of µ-opioid receptors (MOR) have not been evaluated. In C57BL/6 male mice with inflammatory pain provoked by the subplantar administration of complete Freund’s adjuvant (CFA), we evaluated: (1) the antinociceptive actions of 5-fluoro-2-oxindole and its reversion with the HO-1 inhibitor, tin protoporphyrin IX (SnPP); (2) the effects of 5-fluoro-2-oxindole in the protein levels of mitogen-activated protein kinase (MAPK), Nrf2, NADPH quinone oxidoreductase1 (NQO1), heme oxygenase 1 (HO-1), oxidative stress marker (4-hydroxy-2-nonenal; 4-HNE), inducible nitric oxide synthase (NOS2), microglial markers (CD11b/c and IBA-1), and MOR in the spinal cord and/or paw of animals with inflammatory pain; (3) the antinociceptive effects of morphine in 5-fluoro-2-oxindole pre-treated animals. Treatment with 5 and 10 mg/kg of 5-fluoro-2-oxindole inhibited the allodynia and hyperalgesia induced by CFA in a different, time-dependent manner. These effects were reversed by SnPP. Treatment with 5-fluoro-2-oxindole increased the expression of NQO1, HO-1 and MOR and inhibited the CFA-induced upregulation of phosphorylated MAPK, 4-HNE, NOS2, CD11b/c and IBA-1 in spinal cords and/or paws. The local effects of morphine were improved with 5-fluoro-2-oxindole. This work reveals that 5-fluoro-2-oxindole inhibits the plasticity, oxidative and inflammatory responses provoked by peripheral inflammation and potentiates the antinociceptive effects of morphine. Thus, treatment with 5-fluoro-2-oxindole alone and/or combined with morphine are two remarkable new procedures for chronic inflammatory pain management.

Roles of Carbon Monoxide in Leukocyte and Platelet Dynamics in Rat Mesentery during Sevoflurane Anesthesia

2001 ◽  
Vol 95 (1) ◽  
pp. 192-199 ◽  
Author(s):  
Hiroshi Morisaki ◽  
Tomihiro Katayama ◽  
Yoshifumi Kotake ◽  
Masaharu Ito ◽  
Takuya Tamatani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Protoporphyrin Ix ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Sevoflurane Anesthesia ◽  
Mechanically Ventilated ◽  
Rat Mesentery ◽  
Platelet Dynamics

Background Heme oxygenase 1 (HO-1), induced by a variety of stressors, provides endogenous carbon monoxide (CO) and bilirubin, both of which play consequential roles in organs. The current study aimed to examine whether induction of HO-1 and its by-products modulated endothelial interaction with circulating leukocytes and platelets evoked by sevoflurane anesthesia in vivo. Methods Rats, pretreated with or without hemin, were anesthetized with sevoflurane in 100% O2, and lungs were mechanically ventilated. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester and leukocyte behavior in mesenteric venules were visualized during sevoflurane anesthesia at 1,000 frames/s using intravital ultrahigh-speed intensified fluorescence videomicroscopy. To examine the mechanisms for the effects of HO-1 on leukocyte and platelet behavior, these studies were repeated with superfusion of either CO, bilirubin, or Nomega-nitro-L-arginine methyl ester (L-NAME). Results As reported previously, the elevation of sevoflurane concentration evoked adhesive responses of leukocytes, concurrent with platelet margination and rolling. Pretreatment with hemin, a HO-1 inducer, prevented such sevoflurane-elicited changes in the microvessels. These changes were restored by zinc protoporphyrin IX, a HO inhibitor, and repressed by CO but not by bilirubin. During sevoflurane anesthesia, however, nitric oxide suppression by L-NAME deteriorated microvascular flows irrespective of the presence or absence of the HO-1 induction. Conclusions These results indicate that endogenous CO via HO-1 induction attenuates sevoflurane-induced microvascular endothelial interactions with leukocytes and platelets, although local nitric oxide levels appear to dominate microvascular flow in situ.

scholarly journals Cobalt protoporphyrin IX increases endogenous G‐ CSF and mobilizes HSC and granulocytes to the blood

2019 ◽  
Vol 11 (12) ◽  
Author(s):  
Agata Szade ◽  
Krzysztof Szade ◽  
Witold N Nowak ◽  
Karolina Bukowska‐Strakova ◽  
Lucie Muchova ◽  
...  
Keyword(s):  
Protoporphyrin Ix ◽  
Cobalt Protoporphyrin ◽  
Cobalt Protoporphyrin Ix

scholarly journals Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX

2016 ◽  
Vol 120 (3) ◽  
pp. 790-804 ◽  
Author(s):  
I. Assunção-Miranda ◽  
C. Cruz-Oliveira ◽  
R.L.S. Neris ◽  
C.M. Figueiredo ◽  
L.P.S. Pereira ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Protoporphyrin Ix ◽  
Cobalt Protoporphyrin ◽  
Tin Protoporphyrin ◽  
Cobalt Protoporphyrin Ix

Interaction between the carbon monoxide and nitric oxide pathways in the locus coeruleus during fever

Neuroscience ◽  
2012 ◽  
Vol 206 ◽  
pp. 69-80 ◽  
Author(s):  
R.N. Soriano ◽  
M. Kwiatkoski ◽  
M.E. Batalhao ◽  
L.G.S. Branco ◽  
E.C. Carnio
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Locus Coeruleus

scholarly journals Does nitric oxide upregulate activity and expression of heme oxygenase‐1 in the rat locus coeruleus during endotoxemia?

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Renato N Soriano ◽  
Marcelo Kwiatkoski ◽  
Gabriela R Oliveira‐Pelegrin ◽  
Maria JA Rocha ◽  
Luiz GS Branco ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Locus Coeruleus ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes

2005 ◽  
Vol 289 (2) ◽  
pp. H701-H707 ◽  
Author(s):  
Saadet Turkseven ◽  
Adam Kruger ◽  
Christopher J. Mingone ◽  
Pawel Kaminski ◽  
Muneo Inaba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Experimental Diabetes ◽  
Aortic Ring ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Antioxidant Mechanism ◽  
Cobalt Protoporphyrin ◽  
Oxide Synthase

Increased heme oxygenase (HO)-1 activity attenuates endothelial cell apoptosis and decreases superoxide anion (O2−) formation in experimental diabetes by unknown mechanisms. We examined the effect of HO-1 protein and HO activity on extracellular SOD (EC-SOD), catalase, O2−, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) levels and vascular responses to ACh in control and diabetic rats. Vascular EC-SOD and plasma catalase activities were significantly reduced in diabetic compared with nondiabetic rats ( P < 0.05). Upregulation of HO-1 expression by intermittent administration of cobalt protoporphyrin, an inducer of HO-1 protein and activity, resulted in a robust increase in EC-SOD but no significant change in Cu-Zn-SOD. Administration of tin mesoporphyrin, an inhibitor of HO-1 activity, decreased EC-SOD protein. Increased HO-1 activity in diabetic rats was associated with a decrease in iNOS but increases in eNOS and plasma catalase activity. On the other hand, aortic ring segments from diabetic rats exhibited a significant reduction in vascular relaxation to ACh, which was reversed with cobalt protoporphyrin treatment. These data demonstrate that an increase in HO-1 protein and activity, i.e., CO and bilirubin production, in diabetic rats brings about a robust increase in EC-SOD, catalase, and eNOS with a concomitant increase in endothelial relaxation and a decrease in O2−. These observations in experimental diabetes suggest that the vascular cytoprotective mechanism of HO-1 against oxidative stress requires an increase in EC-SOD and catalase.

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