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• W2022254932 endingPage "454" @default.
• W2022254932 startingPage "444" @default.
• W2022254932 abstract "Activation of mast cells and eosinophils is a fundamental process in the pathophysiology of allergic diseases. We have previously reported that the novel enhydrazinone ester CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate) possesses potent anti-inflammatory activity. We have now tested whether the compound also possesses antiallergic and antiasthmatic effects in vitro and in vivo. The compound significantly inhibited degranulation and leukotriene C₄ (LTC₄) release from activated human eosinophils, as well as IgE-dependent degranulation and LTC₄ release from passively sensitized rat basophilic leukemia cells and bone marrow–derived mouse mast cells. In human eosinophils, the drug was more potent in inhibiting degranulation than LTC₄ release {IC₅₀ = 0.4 <i>μ</i>M [confidence interval (CI): 0.1–0.9] versus 3.8 <i>μ</i>M (CI: 0.9–8.3)}, whereas in mast cells the reverse was essentially the case. The drug did not affect stimulus-induced calcium transients in eosinophils but significantly inhibited early phosphorylation of extracellular signal-regulated kinases 1/2 and p38–mitogen-activated protein kinases (MAPK). In vivo, topical application of 4.5–15 mg/kg of the compound significantly inhibited allergen-induced passive cutaneous anaphylaxis in mice. Similarly, in the mouse asthma model, the intranasal administration of 6.5–12.5 mg/kg of the compound significantly inhibited bronchial inflammation and eosinophil accumulation in bronchial lavage fluid, as well as abolishing airway hyper-responsiveness to methacholine. These results show that CEE-1 inhibits the activation of both mast cells and eosinophils in vitro, probably by blocking MAPK-activation pathways, and that these effects are translated into antiallergic and antiasthmatic effects in vivo. The compound, therefore, has potential application in the treatment of asthma and other allergic diseases." @default.
• W2022254932 created "2016-06-24" @default.
• W2022254932 creator A5009707260 @default.
• W2022254932 creator A5041313393 @default.
• W2022254932 creator A5065967997 @default.
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• W2022254932 date "2014-06-10" @default.
• W2022254932 modified "2023-09-25" @default.
• W2022254932 title "Antiallergic and Antiasthmatic Effects of a Novel Enhydrazinone Ester (CEE-1): Inhibition of Activation of Both Mast Cells and Eosinophils" @default.
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• W2022254932 doi "https://doi.org/10.1124/jpet.114.213751" @default.
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• W2022254932 hasPublicationYear "2014" @default.
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