Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00527 (Nedocromil sodium)
 190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We examined the effect of various pharmacological agents on the acute bronchoconstrictor response and airway microvascular leakage in a model of guinea-pig sensitization to trimellitic anhydride (TMA) a cause of low molecular weight occupational asthma in man. 2. Guinea-pigs were given intradermal injections of 0.1 ml of 0.3% TMA in corn oil; 21-28 days later, anaesthetized guinea-pigs were challenged with TMA conjugated to guinea-pig albumin by tracheal instillation. Changes in lung resistance were measured and airway microvascular leakage was quantified by measuring the extravasation of Evans blue dye into the airway tissue. 3. Sensitized guinea-pig (n = 9 in each group) were pretreated with chlorpheniramine (2.5 mg kg-1, i.v.), WEB 2086 (10 micrograms kg-1, i.v.), BW 4AC (50 mg kg-1, i.p.), nedocromil sodium (2% aerosol for 60 s) or vehicle alone. 4. Pretreatment with chlorpheniramine inhibited both the acute bronchoconstrictor response and the increase in airway microvascular leakage. WEB 2086 and nedocromil sodium partially inhibited the bronchoconstrictor response but had no significant effect on airway microvascular leakage. BW 4AC caused a non-significant reduction of the bronchoconstrictor response and airway microvascular leakage. 5. These results indicate that both the bronchoconstrictor response and the airway microvascular response in this model of sensitization is mediated to a large extent by histamine. PAF but not 5-lipoxygenase products also partially mediates the bronchoconstrictor response but not the airway microvascular leakage. Nedocromil sodium partially inhibits the bronchoconstrictor response only.
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PMID:Involvement of inflammatory mediators in the airway responses to trimellitic anhydride in sensitized guinea-pigs. 138 88

The effect of nedocromil sodium on PAF-acether- and antigen-induced bronchoconstriction (BC) and mediator release in lungs from actively sensitized guinea pigs and on the eosinophil content of bronchoalveolar lavage (BAL) was investigated. Guinea pigs were actively sensitized by two subcutaneous injections of 10 micrograms ovalbumin in 1 mg AI(OH)3 at 2-wk intervals. One week after the second (booster) injection, the lungs were removed, perfused in the absence or presence of indomethacin, and challenged at 10-min intervals with PAF-acether (1 and 100 ng) and with ovalbumin (1 micrograms). No inhibition of PAF-acether- and antigen-induced BC or mediator release from sensitized lungs was observed when nedocromil sodium (10 microM) was added directly to the buffer solution. By contrast, when guinea pigs were treated for 1 wk before the experiment with nedocromil sodium (30 mg/kg per day), BC and the release of leukotrienelike material (but not of thromboxane B2) to 1 ng PAF-acether were reduced by around 50% (p less than 0.05) and 62% (p less than 0.05), respectively. No inhibition was observed for 100 ng PAF-acether and 1 micrograms ovalbumin. Furthermore, nedocromil sodium markedly impaired histamine secretion induced by both PAF-acether and antigen administration. Nedocromil sodium did not affect the titers of circulating ovalbumin-specific immunoglobulin G, as detected by an enzyme-linked immunosorbent assay. The 1-wk treatment with nedocromil sodium also reduced markedly the proportion of eosinophils in the BAL of sensitized guinea pigs, whereas it was ineffective when injected once subcutaneously at the dose of 30 mg/kg 2 h before the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protection by nedocromil sodium of active immunization-induced bronchopulmonary alterations in the guinea pig. 216 Feb 13

Antigen challenge of ovalbumin (OA)-sensitized guinea pigs results in significant (p less than 0.05) increases in vascular permeability to Evans blue (EB) dye in the airways, esophagus, and bladder. Mean values +/- SEM in ng EB/mg wet weight tissue for unsensitized versus sensitized animals were: trachea, 23.6 +/- 6.6 versus 92.5 +/- 11.1; main bronchi, 31.1 +/- 12.2 versus 153.1 +/- 14.9; "central" intrapulmonary airways (ipa), 34.6 +/- 11.2 versus 101.3 +/- 6.2; and "peripheral" ipa, 26.2 +/- 6.8 versus 93.5 +/- 13.6. We investigated the involvement of several mediators of inflammation in this process. FPL 55712, a sulfidopeptide leukotriene receptor antagonist, caused significant inhibition of leakage in trachea (to 55.1 +/- 9.8) and main bronchi (91.7 +/- 15.8). Blockade of the cyclooxygenase and lipoxygenase pathways with BW 755C, but not of the cyclooxygenase pathway alone with indomethacin, also significantly reduced EB dye extravasation in trachea (55.1 +/- 18.0), main bronchi (71.7 +/- 23.0), and "central" ipa (62.7 +/- 16.4). The histamine antagonists, chlorpheniramine and cimetidine, only inhibited microvascular leakage in main bronchi (94.4 +/- 20.0). PAF-receptor blockade with the ginkgolide mixture BN 52063 had no effect. Nedocromil sodium, a mast cell stabilizer and an inhibitor of inflammatory cell activation, caused significant inhibition throughout the airways: trachea, 50.4 +/- 10.6; main bronchi, 72.0 +/- 15.3; "central" ipa 61.0 +/- 8.6; "peripheral" ipa 41.9 +/- 12.2. Thus, histamine and lipoxygenase products (in particular, leukotrienes), but not PAF, may mediate the antigen-induced increase in vascular permeability to different degrees in differing regions of the respiratory tract in guinea pigs.
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PMID:Inflammatory mediators involved in antigen-induced airway microvascular leakage in guinea pigs. 284 29

Using the allergen-induced late-phase asthmatic reaction as a working model, we studied the activity of certain inflammatory cells and their reaction to nedocromil sodium. The processes that were examined in vitro included the following: the chemotaxis of purified neutrophils and eosinophils, the early steps of neutrophil and eosinophil activation, and the release of mediators from these cells. Nedocromil sodium strongly inhibited neutrophil mobilization caused by four chemotactic factors (zymosan activated serum, N-formyl-methionyl-leucyl-phenylalanine platelet-activating factor [PAF], and leukotriene B4 [LTB4] and eosinophil mobilization caused by two factors (PAF and LTB4). In vitro treatment of eosinophils from normal subjects with picomolar concentrations of interleukin-3, interleukin-5, or granulocyte-macrophage colony stimulating factor increased the chemotactic responsiveness toward PAF and LTB4 and induced a chemotactic responsiveness toward N-formyl-methionyl-leucyl-phenylalanine and neutrophil activating factor/interleukin-8. The zymosan activated serum-induced chemotactic responsiveness remained unaltered. Nedocromil sodium inhibited the cytokine-primed chemotactic responsiveness to the various chemotaxins, not the influence of the cytokines on the cells. Activation of granulocytes, as measured by Ca2+ influx, was not inhibited by nedocromil sodium. Mediator formation in eosinophils was modified only slightly. These results suggest that inhibiting the mobilization of inflammatory cells in the lung tissue may be an important action of nedocromil sodium. Therefore these effects may be relevant to the treatment of asthma given the role of airway inflammation in this disease process.
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PMID:Effects of nedocromil sodium on in vitro induced migration, activation, and mediator release from human granulocytes. 839 21

Both PAF (10 microM) and bradykinin (0.1-10 microM) increased lysozyme (from submucosal gland serous cells (+138 and +45% for PAF, 10 microM, and bradykinin, 1 microM, respectively) and albumin (mainly active epithelial transport; +387 and +108%) outputs into the ferret tracheal lumen in vitro and reduced the negativity of the potential difference (PD: -33 and -17%) across the trachea. Since PAF can cause bronchial smooth muscle hyperresponsiveness, we tested whether these effects were interactive, and if PAF would increase the actions of bradykinin. The bradykinin-induced lysozyme and albumin outputs were more than trebled and the PD change was enhanced by PAF, after the immediate secretory effects of the latter had returned to baseline. The secretory and PD responses to PAF were all prevented by the PAF-antagonist WEB 2086 and by a combination of the free-radical scavengers catalase and SOD, indicating that PAF may act on specific receptors to release free-radicals. Nedocromil sodium inhibited the increase in lysozyme and albumin outputs produced by PAF, but had no effect on the PD response. None of the tracheal responses to bradykinin was modified by WEB 2086, catalase and SOD, or nedocromil sodium. The secretory and PD hyperresponsiveness to bradykinin caused by PAF was prevented by WEB 2086 and by catalase and SOD. Nedocromil sodium greatly inhibited the lysozyme and albumin hyperresponsiveness but had no effect on the PD response. Thus PAF may release more than one type of radical which have differential effects on serous cells and albumin transport compared with PD; nedocromil sodium may act only against the radical causing the secretory effects.
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PMID:PAF-induced secretory hyperresponsiveness in the ferret trachea to bradykinin and its pharmacological inhibition. 951 26