Phorbol ester-induced dermal inflammation in mice: evaluation of inhibitors of 5-lipoxygenase and antagonists of leukotriene B4 receptor.
J Lipid Mediat Cell Signal
; 10(3): 213-28, 1994 Sep.
Article
em En
| MEDLINE
| ID: mdl-7812673
ABSTRACT
In the present investigation, the effects of selective inhibitors of 5-lipoxygenase (5-LO), zileuton and TZI-41127, E-6080, AA-861 and antagonists of leukotriene B4 (LTB4) receptors, SC-41930, and SC-51146 and a selective cyclooxygenase inhibitor, indomethacin, were examined in TPA-induced acute mouse dermal inflammation. Topical application of all these agents, except indomethacin, resulted in marked attenuation of TPA-induced edema and influx of neutrophils reflected in myeloperoxidase measurements. Topically applied SC-41930 attenuated TPA-induced edema and neutrophil influx in a dose-related manner. Oral administration of LTB4 receptor antagonists either as a pre-treatment or post-treatment attenuated TPA-induced edema and influx of neutrophils. The O-demethyl analog of SC-41930, SC-37920, which was nearly 1000-fold less active than SC-41930 in LTB4 receptor binding assays, was inactive in inflammation assays, suggesting a role for LTB4 in this response. Zileuton and TZI-41127 were more effective as anti-inflammatory agents following oral administration than after i.p. administration. Intraperitoneally administered indomethacin attenuated edema response but not influx of neutrophils. Taken together, these results suggest a role for leukotrienes in acute inflammation induced by TPA and possible utility of this model to test in vivo 5-LO inhibitors and LTB4 receptor antagonists.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetato de Tetradecanoilforbol
/
Inibidores de Lipoxigenase
/
Receptores do Leucotrieno B4
/
Dermatite de Contato
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Lipid Mediat Cell Signal
Assunto da revista:
BIOQUIMICA
Ano de publicação:
1994
Tipo de documento:
Article