Calcium‐independent NO‐synthase activity and nitrites/nitrates production in transient focal cerebral ischaemia in mice

Grandati, M.; Verrecchia, C.; Revaud, M. L.; Allix, Monique; Boulu, R; Plotkine, Michel

doi:10.1038/sj.bjp.0701427

Cited by 89 publications

(49 citation statements)

References 39 publications

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“…Whereas a trend toward increased nitrite release was detected 24 hours after induction of cerebral ischemia, nitrite release was significantly increased at day 2. Interestingly, such predominantly delayed NO generation is in accordance with the recent detection of NO metabolites in brain homogenates predominantly 3 days after transient cerebral ischemia 22 and agrees exactly with the observation of subacute glial activation and intracerebral migration of macrophages after 2 days at sites of ischemic injury. 23,24 These cells harbor the subacutely synthesized iNOS 19,22 that mediates generation of much larger quantities of NO 25 than the constitutive isoenzymes held responsible for NO production in acute stroke.…”

Section: Discussionsupporting

confidence: 72%

“…Interestingly, such predominantly delayed NO generation is in accordance with the recent detection of NO metabolites in brain homogenates predominantly 3 days after transient cerebral ischemia 22 and agrees exactly with the observation of subacute glial activation and intracerebral migration of macrophages after 2 days at sites of ischemic injury. 23,24 These cells harbor the subacutely synthesized iNOS 19,22 that mediates generation of much larger quantities of NO 25 than the constitutive isoenzymes held responsible for NO production in acute stroke. 26 In such an environment, further cerebral injury associated with insertion of the dialysis probes could trigger a maximal iNOS-dependent NO generation.…”

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confidence: 99%

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Subacute But Not Acute Generation of Nitric Oxide in Focal Cerebral Ischemia

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Ragoschke

et al. 2000

Stroke

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Background and Purpose-Excessive release of nitric oxide (NO) has been implicated in the pathophysiology of neurodegeneration in ischemic stroke. We compared intracerebral release of indicators of NO generation at the acute and subacute stages of transient focal cerebral ischemia. Methods-In vivo microdialysis in the rat striatum was performed at the acute (first hours) and subacute (after 24 or 48 hours) stages of cerebral ischemia or sham operation to monitor intracerebral release of the stable NO metabolites nitrite and nitrate. Results-Whereas only a nonsignificant trend toward increased release of these NO metabolites was evidenced in acute cerebral ischemia, a significant NO generation was observed subacutely, 48 hours after induction of cerebral ischemia. Aminoguanidine, a selective inhibitor of inducible NO synthase, suppressed this delayed release of nitrite and nitrate. Conclusions-Whereas these observations do not support a major NO generation in acute cerebral ischemia, they indicate an inducible NO synthase-dependent NO generation predominantly at the subacute phase of ischemic neurodegeneration. Therefore, NO generation may play a pathophysiological role in delayed ischemic neurodegeneration. (Stroke. 2000;31:2208-2211.)Key Words: cerebral ischemia, focal Ⅲ nitric oxide Ⅲ nitric oxide synthase Ⅲ rats W hereas in low concentrations (nanomolar range), nitric oxide (NO) plays a physiological role in neuronal signaling, in high concentrations (micromolar range) this molecule is enormously cytotoxic. 1 The production of NO, itself a free radical, promotes tissue injury, eg, by reaction with superoxide anion to produce the extremely toxic peroxynitrite or by interaction with proteins, transition metals, and iron-sulfur-containing or heme-containing compounds. 2,3 Excessive NO generation has been implicated in ischemic neurodegeneration 4,5 and is currently intensely studied as a therapeutic target in ischemic stroke. 5,6 The rapidly decaying gas NO cannot be detected directly. However, changes in concentrations of the stable NO oxidation products nitrite and nitrate allow estimation of NO generation. 7 Recently, extracellular release of NO metabolites in the central nervous system has been reported in acute global 8 -11 or focal 12,13 cerebral ischemia with the use of in vivo microdialysis. This technique allows repeated sampling of brain tissue perfusate in the same freely moving rat. 14 The results of these studies were conflicting since they showed decreased or increased concentrations of NO metabolites for minutes or hours. More importantly, whereas formation of NO metabolites has been monitored with this technique only in the acute stage of focal cerebral ischemia, there is, to our knowledge, no information about a possible NO generation in the subacute phase (ie, beyond 24 hours). This uncertainty clearly contrasts with the general belief that NO is a key molecule in the pathogenesis of ischemic neurodegeneration and represents an important therapeutic target in ischemic stroke. 5 In this study we...

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Section: Discussionsupporting

confidence: 72%

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confidence: 99%

Subacute But Not Acute Generation of Nitric Oxide in Focal Cerebral Ischemia

Faßbender

Fatar

Ragoschke

et al. 2000

Stroke

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“…Increased generation of NO after cerebral ischemia has been reported by measurements of brain nitrite in mice [9]. Moreover, the immunohistochemical and biochemical analysis demonstrated the increment of nitrotyrosine in the brains of Alzehimer's disease or Parkinson's disease patients [10,11].…”

Section: Resultsmentioning

confidence: 96%

“…As shown in Figure 1, all the tested fractions effectively inhibited LPS-induced NO production in BV2 cells. Among these fractions, the EtOAc fraction which showed the most significant NO production inhibitory effect and the n-hexane fraction, the most abundant fraction, were used for the isolation of active compounds to yield five anthraquinones (1 -5) such as chrysophanol (1), emodin (2), aloeemodin (3), emodin 8-O-b-D-glucopyranoside (4) and trihydroxy anthraquinone (5), and four flavonoids including kaempferol (6), chrysoeriol (7), kaempferol 3-gentiobioside (8) and isorhamnetin (9). The chemical structures of these compounds were determined by comparison of their spectroscopic data with those previously reported [15 -18] (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Chemical constituents isolated from Polygala japonica leaves and their inhibitory effect on nitric oxide production in vitro

Kim¹,

Jang

Lee

et al. 2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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A methanolic extract of dried leaves of Polygala japonica Houtt (Polygalaceae) significantly attenuated nitric oxide production in lipopolysaccharide-simulated BV2 microglia. Five anthraquinones chrysophanol (1), emodin (2), aloe-emodin (3), emodin 8-O-b-D-glucopyranoside (4) and trihydroxy anthraquinone (5), and four flavonoids kaempferol (6), chrysoeriol (7), kaempferol 3-gentiobioside (8) and isorhamnetin (9) were isolated from the methanolic extract using bioactivity-guided fractionation. Among them, compounds 1-4, 6 and 7 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglia at the concentrations ranging from 1.0 to 100.0 mM.

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“…The content of NO x in mouse brain and spinal cord were determined as previously described with minor modification. 14) Brain and spinal cord of mice were homogenized in 3 volume distilled water and centrifuged at 15000 g for 20 min at 4°C. Fifty microliters of supernatant of tissue homogenate was mixed with 20 ml of 0.31 M potassium phosphate buffer (pH 7.5), 10 ml of 0.86 mM b-nicotinamide adenine dinucleotide phosphate (b-NADPH), 10 ml of 0.11 mM flavin adenine dinucleotide (FAD) and 20 mU of nitrate reductase.…”

Section: Methodsmentioning

confidence: 99%

Antinociceptive Effects of St. John's Wort, Harpagophytum Procumbens Extract and Grape Seed Proanthocyanidins Extract in Mice

Uchida

Hirai

Hatanaka³

et al. 2008

Biological & Pharmaceutical Bulletin

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Currently, the consumption of dietary supplement containing botanical products and foods is growing at a remarkable speed, in terms of the promotion of health or prevention and treatment of diseases. The extract from Hypericum perforatum (St. John's wort, SJW) possess clinical efficacy in the therapy of mild to moderate depression. 1,2) The most important constituents of SJW are phloroglucinols such as hyperforin and pseudohyperforin, naphthodianthrones such as hypericin and pseudohypericin, in addition to flavonoids such as rutin, quercetin, quercitrin. Several in vitro studies have indicated that SJW and hyperforin may act via a blockade of reuptake of serotonin, noradrenaline and dopamine in similar manner as most of the current antidepressants such as tricyclic antidepressants, [3][4][5] which have been known to exhibit antinociceptive properties by monoamine reuptake blockade.Harpagophytum procumbens extract (HPE) and Grape seed proanthocyanidins extract (GSPE) have been reported to exert anti-inflammatory activity in rodents.6-8) Harpagophytum procumbens commonly known as Devil's claw is an herbaceous plant, growing specifically in Southern Africa. Preparations of its secondary roots contain iridoid glycosides, mainly harpagoside, harpagogide and procumbide. HPE have been shown to possess clinical efficacy in the treatment of degenerative rheumatoid arthritis, osteoarthritis and tendonitis. [6][7][8] In addition, experimental study has revealed antiinflammatory activity of HPE in Freund's adjuvant-induced arthritis model. 9) Proanthocyanidins are naturally occurring polyphenolic compounds widely available in fruits, vegetables, nuts, seeds, flowers and bark. Grape seed proanthocyanidins, a combination of biologically active polyphenolic flavonoids including oligomeric proanthocyanidins, have been shown to exert a novel spectrum of biological, pharmacological, therapeutic and chemoprotective properties against oxygen free radicals and oxidative stress. GSPE protects against free radicals models and has exhibited superior antioxidant performance as compared to vitamin C, E and b-carotene. 10)Previous studies with antidepressant activity of SJW and anti-inflammatory effects of HPE and GSPE have led to the idea that these herbal products exert antinociceptive action. Thus, the aim of this study was to clarify the antinociceptive properties of SJW, HPE and GSPE after oral administration to mice with mechanisms that might potentially underlie these activities. The effects of these herbal extracts on the antinociception and plasma and brain concentrations of morphine were also examined. MATERIALS AND METHODSDrugs SJW and HPE were kindly donated by Indena (Milan, Italy). SJW was standardized to the content of hypericin (0.3%) and hyperforin (3.2%) and HPE was also standardized to the content of harpagoside (1.9%). GSPE was kindly supplied by Kikkoman Co. (Chiba, Japan), and standardized to the content of proanthocyanidin (83.9%). Morphine hydrochloride was purchased from Takeda Pharmaceutical Co. (Osaka, Japan). A...

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Calcium‐independent NO‐synthase activity and nitrites/nitrates production in transient focal cerebral ischaemia in mice

Cited by 89 publications

References 39 publications

Subacute But Not Acute Generation of Nitric Oxide in Focal Cerebral Ischemia

Subacute But Not Acute Generation of Nitric Oxide in Focal Cerebral Ischemia

Chemical constituents isolated from Polygala japonica leaves and their inhibitory effect on nitric oxide production in vitro

Antinociceptive Effects of St. John's Wort, Harpagophytum Procumbens Extract and Grape Seed Proanthocyanidins Extract in Mice

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