Evaluation of the cutaneous anti-inflammatory activity of azaspiranes
| Autor: | D. E. Griswold, M. Chabot-Fletcher, J. J. Breton, L. D. Martin, Alison M. Badger |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.drug_class Administration Topical Immunology Prostaglandin Inflammation Pharmacology Dermatitis Contact Leukotriene B4 Dinoprostone Monocytes Anti-inflammatory Cell Line Mice chemistry.chemical_compound Piperidines In vivo medicine Animals Edema Humans Spiro Compounds Peroxidase Mice Inbred BALB C Arachidonate 5-Lipoxygenase Arachidonic Acid biology Anti-Inflammatory Agents Non-Steroidal NF-kappa B Membrane Proteins Ear In vitro Isoenzymes Biochemistry chemistry Prostaglandin-Endoperoxide Synthases Myeloperoxidase Cyclooxygenase 1 biology.protein Tetradecanoylphorbol Acetate Arachidonic acid Cyclooxygenase medicine.symptom Immunosuppressive Agents |
| Zdroj: | Inflammation Research. 47:56-61 |
| ISSN: | 1420-908X 1023-3830 |
| Popis: | Objective and Design: The ability of azaspiranes to modulate the acute inflammatory response in models of skin inflammation was examined.¶Material: The in vivo experiments involved the use of 5–6 age-matched male Balb/c inbred mice (22–25 g) per treatment group and a control group of 8–10 animals. In vitro mechanistic studies used RBL-1 and U937 cells lines and freshly isolated human monocytes.¶Treatment: Arachidonic acid (AA) (2 mg/20 ul in acetone) or PMA (phorbol myristate acetate) (4 ug/20 ul) were applied topically. SK&F 106615 and SK&F 106610 were administered topically either dissolved in acetone or dimethylacetamide just after the application of the irritant. Isolated cells were treated with the compounds dissolved in DMSO.¶Methods: The thickness and influx of neutrophils into the treated ears was measured as was the effects of the azaspiranes on 5-lipoxygenase activity, cyclooxygenase activity, prostaglandin and leukotriene synthesis, and the activation of the transcription factor NF-κB.¶Results: SK&F 106615 and SK&F 106610 significantly reduced inflammation in the AA- and PMA-induced inflammation models (p < 0.05) with ED50's of 179 and 120 mg/ear for edema and myeloperoxidase, respectively. The compounds did not inhibit eicosanoid biosynthesis, have a direct effect on 5-lipoxygenase or cyclooxygenase enzymes, or inhibit NF-κB.¶Conclusions: The potent anti-inflammatory and immunomodulatory activities of the azaspiranes observed in these and other studies appear to be mediated by a novel mechanism. |
| Databáze: | OpenAIRE |
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