Evaluation of 5-lipoxygenase inhibitors, zileuton, A-78773 and ICI-D-2138 in an ionophore (A-23187)-induced pleural inflammation model in the rat.
Life Sci
; 53(9): PL147-52, 1993.
Article
en En
| MEDLINE
| ID: mdl-8394967
ABSTRACT
Intrapleural injection of A-23187 (10 micrograms), a calcium ionophore, elicited rapid increase in biosynthesis of prostaglandins and leukotrienes in a time-dependent manner. 6-Keto-prostaglandin-F1 alpha (6-KPA) was the principal cyclooxygenase product with modest increases in levels of thromboxane B2 and prostaglandin-E2. Orally administered indomethacin, a selective cyclooxygenase inhibitor, and three selective 5-lipoxygenase inhibitors, zileuton, A-78773 and ICI-D-2138 markedly attenuated respective arachidonate pathways with projected ED50 values of < 1-2 mg/kg. Furthermore, a single oral administration of either ICI-D-2138 or A-78773 (each 20 mg/kg, po) resulted in persistent inhibition of 5-lipoxygenase pathway for up to 24 hr. These results indicate zileuton, A-78773 and ICI-D-2138 to be potent and selective inhibitors of 5-LO and document the utility of A-23187-induced pleural inflammation in evaluating efficacy of inhibitors of arachidonic acid metabolism in vivo.
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Bases de datos:
MEDLINE
Asunto principal:
Pleuresia
/
Calcimicina
/
Inhibidores de la Lipooxigenasa
Idioma:
En
Revista:
Life Sci
Año:
1993
Tipo del documento:
Article