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
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.