Artemether: a new therapeutic strategy in experimental rheumatoid arthritis.
The current research was designed to determine the effect of artemether in treatment of experimental rheumatoid arthritis. Collagen-induced arthritis was induced in Lewis rats. The intramusculary administration of artemether (ART) and intraperitoneally injection of methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was taken intermittently. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ART and MTX were assessed using fibrosarcoma cell line. Data showed that i.m. injection of ART 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 a reduced inflammatory cell infiltrate in joints of treated rats; tissue edema, and bone erosion in the paws were markedly reduced following ART therapy. Furthermore, our radiography results paralleled our histological findings. Cytotoxicity analysis of ART showed greater tolerability compared with MTX. Treatment with ART significantly diminished NO formation in treated rats compared with nontreated controls. Our data shed light on the therapeutic efficacy of artemether in experimental rheumatoid arthritis compared with a choice drug (methotrexate), and it may be offered as a second-line drug in treatment of rheumatoid arthritis.
Cuzzocrea
Salvatore
S
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Saadat
Farshid
F
Di Paola
Rosanna
R
Mirshafiey
Abbas
A
D000818:Animals; D000906:Antibodies / Q000097:blood; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000517:prevention & control; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D000906:Antibodies; D000962:Antimalarials; D018501:Antirheumatic Agents; D037621:Artemisinins; D024043:Collagen Type II; D009569:Nitric Oxide; D000077549:Artemether; D020778:Matrix Metalloproteinase 2; D008727:Methotrexate