Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 1998
Evaluation of the cutaneous anti-inflammatory activity of azaspiranes.
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Griswold D E, Martin L D, Badger A M, Breton J, Chabot-Fletcher M
Аннотация
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 microl in acetone) or PMA (phorbol myristate acetate) (4 microg/20 microl) 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-kappaB.
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-kappaB.
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.
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 microl in acetone) or PMA (phorbol myristate acetate) (4 microg/20 microl) 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-kappaB.
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-kappaB.
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.
Предметные рубрики MeSH
Administration, TopicalAnimalsAnti-Inflammatory Agents, Non-SteroidalArachidonate 5-LipoxygenaseArachidonic AcidCell LineCyclooxygenase 1Dermatitis, ContactDinoprostoneEarEdemaHumansImmunosuppressive AgentsIsoenzymesLeukotriene B4MaleMembrane ProteinsMiceMice, Inbred BALB CMonocytesNF-kappa BPeroxidasePiperidinesProstaglandin-Endoperoxide SynthasesSpiro CompoundsTetradecanoylphorbol Acetate