title: Effect of pyrimethamine in experimental rheumatoid arthritis.
abstract: 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.
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farshid
authors.initials: F
authors.lastname: Saadat
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Mohammad
authors.initials: M
authors.lastname: Pezeshki
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khorramizadeh
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sedaghat
authors.forename: Alireza
authors.initials: A
authors.lastname: Razavi
authors.forename: Abbas
authors.initials: A
authors.lastname: Mirshafiey
mesh_terms: 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
chemical_list: D000906:Antibodies; D009569:Nitric Oxide; D020778:Matrix Metalloproteinase 2; D011739:Pyrimethamine