Design of a new line in treatment of experimental rheumatoid arthritis by artesunate

被引:52
作者
Mirshafiey, A.
Saadat, F.
Attar, M.
Di Paola, R.
Sedaghat, R.
Cuzzocrea, S.
机构
[1] Univ Tehran, Sch Publ Hlth, Dept Immunol, Tehran 14155, Iran
[2] Univ Messina, Sch Med, Inst Pharmacol, Messina, Italy
[3] Univ Shahed, Sch Med, Dept Pathol, Tehran, Iran
关键词
anti-inflammatory; antimalarial drugs; artemisinin; artesunate; immunosuppressive; nitric oxide; rheumatoid arthritis;
D O I
10.1080/08923970600927447
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:397 / 410
页数:14
相关论文
共 45 条
[31]   INHIBITION OF TUMOR-NECROSIS-FACTOR (TNF) PRODUCTION BY ANTIMALARIAL-DRUGS USED IN CEREBRAL MALARIA [J].
KWIATKOWSKI, D ;
BATE, C .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1995, 89 (02) :215-216
[32]   Immunization with alum-collagen II complex suppresses the development of collagen-induced arthritis in rats by deviating the immune response [J].
Mattsson, L ;
Lorentzen, JC ;
Svelander, L ;
Bucht, A ;
Nyman, U ;
Klareskog, L ;
Larsson, P .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1997, 46 (06) :619-624
[33]   Relationship between Th1/Th2 cytokine patterns and the arthritogenic response in collagen-induced arthritis [J].
Mauri, C ;
Williams, RO ;
Walmsley, M ;
Feldmann, M .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (07) :1511-1518
[34]  
Mirshafiey A, 2000, SCAND J IMMUNOL, V52, P278
[35]   A randomized, placebo-controlled, double-blind trial on sulfadoxine-pyrimethamine alone or combined with artesunate or amodiaquine in uncomplicated malaria [J].
Mockenhaupt, FP ;
Ehrhardt, S ;
Dzisi, SY ;
Bousema, JT ;
Wassilew, N ;
Schreiber, J ;
Anemana, SD ;
Cramer, JP ;
Otchwemah, RN ;
Sauerwein, RW ;
Eggelte, TA ;
Bienzle, U .
TROPICAL MEDICINE & INTERNATIONAL HEALTH, 2005, 10 (06) :512-520
[36]   TNF-ALPHA DOMINATES CYTOKINE MESSENGER-RNA EXPRESSION IN LYMPHOID-TISSUES OF RATS DEVELOPING COLLAGEN-INDUCED AND OIL-INDUCED ARTHRITIS [J].
MUSSENER, A ;
KLARESKOG, L ;
LORENTZEN, JC ;
KLEINAU, S .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1995, 42 (01) :128-134
[37]   SUPPRESSION OF COLLAGEN-INDUCED ARTHRITIS BY AN ANGIOGENESIS INHIBITOR, AGM-1470, IN COMBINATION WITH CYCLOSPORINE - REDUCTION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) [J].
OLIVER, SJ ;
CHENG, TP ;
BANQUERIGO, ML ;
BRAHN, E .
CELLULAR IMMUNOLOGY, 1995, 166 (02) :196-206
[38]   Modifying national malaria treatment policies in Peru [J].
Ruebush, TK ;
Neyra, D ;
Cabezas, C .
JOURNAL OF PUBLIC HEALTH POLICY, 2004, 25 (3-4) :328-345
[39]   Nitric oxide: A key mediator in the early and late phase of carrageenan-induced rat paw inflammation [J].
Salvemini, D ;
Wang, ZQ ;
Wyatt, PS ;
Bourdon, DM ;
Marino, MH ;
Manning, PT ;
Currie, MG .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 118 (04) :829-838
[40]  
Sun X Z, 1991, Zhong Xi Yi Jie He Za Zhi, V11, P37