Effects of ER-34122, a novel dual 5-lipoxygenase/cyclooxygenase inhibitor, on indices of early articular lesion in MRL/MpJ-lpr/lpr mice.
OBJECTIVE
To investigate effects of ER-34122, a novel dual 5-lipoxygenase (LOX)/cyclooxygenase (COX) inhibitor, and indomethacin on progression of articular lesions in MRL/MpJ-lpr/lpr (MRL/1) mice.


METHODS
100 male MRL/l mice.


METHODS
ER-34122 (1-100 mg/kg) and indomethacin (1 mg/kg) were orally administered once a day to MRL/l 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/l mice arthritis. Serum levels of rheumatoid factor were measured by using enzyme-linked immunosorbent assay.


RESULTS
Articular lesions in the late stage of MRL/l mice arthritis were characterized by cartilage degeneration and pannus formation which were severer than those in the early stage. Polymorphonuclear leukocyte (PMN) infiltration and subsynovial soft tissue edema were observed as characteristic lesions in the early stage. ER-34122 suppressed progression of PMN infiltration, subsynovial soft tissue edema and multiplication of synovial lining cells in the early stage of the arthritis, even though it had no significant effect 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 arthritis at the examined dose.


CONCLUSIONS
These results disclosed that ER-34122, a dual LOX/COX inhibitor, has anti-inflammatory activity in the early stage of the spontaneous arthritis.
Horizoe
T
T
Eisai Co., Ltd., Tsukuba Research Laboratories, Ibaraki, Japan.
Nagakura
N
N
Chiba
K
K
Shirota
H
H
Shinoda
M
M
Numata
H
H
Kobayashi
S
S
Abe
C
C
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001549:Benzamides / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007213:Indomethacin / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009929:Organ Size / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*
C116824:5-((1,5-bis(4-methoxyphenyl)pyrazol-3-yl)dimethoxymethyl)-2-chlorobenzamide; D001549:Benzamides; D016861:Cyclooxygenase Inhibitors; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D007213:Indomethacin