Design of a New Line in Treatment of Experimental Rheumatoid Arthritis by Artesunate

• Published in: Immunopharmacology and immunotoxicology 2006, Vol.28 (3), p.397-410
• Main Authors: Mirshafiey, A., Saadat, F., Attar, M., Di Paola, R., Sedaghat, R., Cuzzocrea, S.
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Antimalarial Drugs; Artemisinin; Artemisinins - administration & dosage; Artemisinins - therapeutic use; Artesunate; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Arthritis, Experimental - metabolism; Autoantibodies - analysis; Cell Line, Tumor; Cell Survival - drug effects; Collagen Type II - immunology; Collagenases - metabolism; Edema - chemically induced; Edema - drug therapy; Edema - immunology; Foot Injuries - chemically induced; Foot Injuries - drug therapy; Foot Injuries - immunology; Hindlimb - diagnostic imaging; Hindlimb - injuries; Hindlimb - ultrastructure; Humans; Immunosuppressive; Inflammation - chemically induced; Inflammation - immunology; Inflammation - pathology; Injections, Intradermal; Injections, Intraperitoneal; Male; Matrix Metalloproteinase Inhibitors; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Nitric Oxide; Nitric Oxide - metabolism; Radiography; Rats; Rats, Inbred Lew; Rheumatoid Arthritis; Sesquiterpenes - administration & dosage; Sesquiterpenes - therapeutic use; Time Factors
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1080/08923970600927447

This study was aimed to evaluate the therapeutic potency of a new antimalarial drug, artesunate, in an experimental model of rheumatoid arthritis. Collagen-induced arthritis (CIA) was induced in Lewis rats.The intraperitoneally administration of artesunate (ARS) and methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was intermittent. 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 ARS and MTX were assessed using fibrosarcoma cell line. Our results showed that i.p. injection of artesunate 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 cells infiltrate in joints of treated rats, and tissue edema and bone erosion in the paws were markedly reduced following ARS therapy. Moreover, our radiographic results paralleled histological findings. Cytotoxicity analysis of ARS showed greater tolerability compared with MTX. Treatment with ARS significantly diminished nitric oxide formation in treated rats compared with untreated controls. Our findings revealed the therapeutic efficacy of artesunate in experimental rheumatoid arthritis compared with a choice drug (methotrexate). This result may recommend it as a second-line drug in the treatment of rheumatoid arthritis.