Effect of pyrimethamine in experimental rheumatoid arthritis.
BACKGROUND
Recent evidence has shown that the antimalarials are useful drugs in the treatment of various rheumatic diseases. The present study was designed to test the therapeutic effect of pyrimethamine (PYR) in collagen-induced arthritis (CIA).


METHODS
CIA was induced in Lewis rats. The intraperitoneal administration of PYR and methotrexate (MTX) were started on day 25 post-immunization and continued until final assessment on day 35. During this period, clinical examination was performed intermittently. Anti-C II Ab and nitric oxide (NO) synthesis were measured. The paws and knees were then removed for histopathology and radiography assay. The biocompatibility of PYR and MTX were assessed using a fibrosarcoma cell line.


RESULTS
Data showed that i.p. injection of pyrimethamine to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed reduced inflammatory cell infiltrate in the joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following PYR therapy. Moreover, our radiography results paralleled our histological findings. Cytotoxicity analysis of PYR showed greater tolerability compared with MTX. Treatment with PYR significantly diminished nitric oxide formation in treated rats compared with untreated controls.


CONCLUSIONS
Our findings shed light on the therapeutic efficacy of pyrimethamine in experimental rheumatoid arthritis compared with a choice drug (methotrexate), which may recommended it as a second-line drug in the treatment of rheumatoid arthritis.
Saadat
Farshid
F
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Cuzzocrea
Salvatore
S
Di Paola
Rosanna
R
Pezeshki
Mohammad
M
Khorramizadeh
Mohammad Reza
MR
Sedaghat
Mohammad
M
Razavi
Alireza
A
Mirshafiey
Abbas
A
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D011739:Pyrimethamine / Q000627:therapeutic use*; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew
D000906:Antibodies; D009569:Nitric Oxide; D020778:Matrix Metalloproteinase 2; D011739:Pyrimethamine