Effects of ER-34122, a novel dual 5-lipoxygenase/cyclooxygenase inhibitor,on indices of early articular lesion in MRL/MpJ-lpr/lpr mice

Citation
T. Horizoe et al., Effects of ER-34122, a novel dual 5-lipoxygenase/cyclooxygenase inhibitor,on indices of early articular lesion in MRL/MpJ-lpr/lpr mice, INFLAMM RES, 48(8), 1999, pp. 432-436
Citations number
18
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INFLAMMATION RESEARCH
ISSN journal
1023-3830 → ACNP
Volume
48
Issue
8
Year of publication
1999
Pages
432 - 436
Database
ISI
SICI code
1023-3830(199908)48:8<432:EOEAND>2.0.ZU;2-0
Abstract
Objective and Design: To investigate effects of ER-34122, a novel dual 5-li poxygenase (LOX)/cyclooxygenase (COX) inhibitor, and indomethacin on progre ssion of articular lesions in MRL/MpJ-1pr/1pr (MRL/1) mice. Material: 100 male MRL/1 mice. Treatment: ER-34122 (1-100 mg/kg) and indomethacin (1 mg/kg) were orally ad ministered once a day to MRL/1 mice from 6 to 10 or 16 weeks old. Methods: Articular lesions were analyzed histopathologically in the early ( 10 weeks old) or late (16 weeks old) stages of MRL/1 mice arthritis. Serum levels of rheumatoid factor were measured by using enzyme-linked immunosorb ent assay. Results: Articular lesions in the late stage of MRL/1 mice arthritis were c haracterized by cartilage degeneration and pannus formation which were seve rer than those in the early stage. Polymorphonuclear leukocyte (PMN) infilt ration and subsynovial soft tissue edema were observed as characteristic le sions in the early stage. ER-34122 suppressed progression of PMN infiltrati on, subsynovial soft tissue edema and multiplication of synovial lining cel ls in the early stage of the arthritis, even though it had no significant e ffect on other indices of articular lesion, enlargement of lymph nodes and serum levels of rheumatoid factors. On indices of late articular lesion, ER -34122 had no significant beneficial effects. Neither in the early nor late stage, indomethacin, a COX inhibitor, had significant effect on the arthri tis at the examined dose. Conclusions: These results disclosed that ER-34122, a dual LOX/COX inhibito r, has anti-inflammatory activity in the early stage of the spontaneous art hritis.