Mirshafiey A, Saadat F, Attar M, Di Paola R, Sedaghat R, Cuzzocrea S
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Immunopharmacol Immunotoxicol. 2006;28(3):397-410. 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.
本研究旨在评估一种新型抗疟药物青蒿琥酯在类风湿性关节炎实验模型中的治疗效果。在Lewis大鼠中诱导胶原诱导性关节炎(CIA)。在免疫后第25天开始腹腔注射青蒿琥酯(ARS)和甲氨蝶呤(MTX),并持续至第35天进行最终评估。在此期间,进行间歇性临床检查。检测抗II型胶原抗体(CII Ab)和一氧化氮合成。然后取出爪子和膝盖进行组织病理学和放射学检测。使用纤维肉瘤细胞系评估ARS和MTX的生物相容性。我们的结果表明,向患有关节炎的大鼠腹腔注射青蒿琥酯可显著减轻爪部水肿。与未治疗的大鼠相比,这种有益效果与抗CII抗体反应的显著降低有关。组织病理学评估显示,治疗大鼠关节中的炎性细胞浸润减少,ARS治疗后爪部的组织水肿和骨质侵蚀明显减轻。此外,我们的放射学结果与组织学发现一致。ARS的细胞毒性分析显示,与MTX相比,其耐受性更好。与未治疗的对照组相比,ARS治疗显著减少了治疗大鼠体内一氧化氮的形成。我们的研究结果揭示了与一种对照药物(甲氨蝶呤)相比,青蒿琥酯在实验性类风湿性关节炎中的治疗效果。这一结果可能使其成为类风湿性关节炎治疗中的二线药物。