Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats.
Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats.
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DOI：
10.1186/ar1801
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发表时间：
2005
影响因子：
4.9
通讯作者：
Sano H
中科院分区：
文献类型：
--
作者：
Omoto A;Kawahito Y;Prudovsky I;Tubouchi Y;Kimura M;Ishino H;Wada M;Yoshida M;Kohno M;Yoshimura R;Yoshikawa T;Sano H
四硫代钼酸盐（TM），一种为威尔逊氏病开发的药物，通过降低全身铜水平产生抗血管生成和抗炎作用。TM疗法已被证明在动物肿瘤模型和癌症患者中有效抑制肿瘤生长。我们假设TM可用于治疗类风湿性关节炎，并检查了TM对急性炎性关节炎和炎性恶病质模型大鼠中抗炎剂诱导的关节炎的疗效。TM延迟了临床关节炎的发作，并抑制了关节炎的严重程度。组织学检查显示TM可显著减少滑膜增生和关节组织中炎性细胞的浸润。有趣的是，TM可以抑制血清滑膜组织中血管内皮生长因子的表达，尤其是在内皮细胞和巨噬细胞中。此外，血管翳形成的程度，导致骨破坏，与血管内皮生长因子在血清中的含量相关。在TM处理的大鼠异常中没有死亡。TM还抑制炎性恶病质。我们认为，TM诱导的铜缺乏是一种有效的方法，既可以抑制类风湿关节炎的进展，副作用最小，又可以改善类风湿关节炎患者的健康。
Tetrathiomolybdate (TM), a drug developed for Wilson's disease, produces an anti-angiogenic and anti-inflammatory effect by reducing systemic copper levels. TM therapy has proved effective in inhibiting the growth of tumors in animal tumor models and in cancer patients. We have hypothesized that TM may be used for the therapy of rheumatoid arthritis and have examined the efficacy of TM on adjuvant-induced arthritis in the rat, which is a model of acute inflammatory arthritis and inflammatory cachexia. TM delayed the onset of and suppressed the severity of clinical arthritis on both paw volume and the arthritis score. Histological examination demonstrated that TM significantly reduces the synovial hyperplasia and inflammatory cell invasion in joint tissues. Interestingly, TM can inhibit the expression of vascular endothelial growth factor in serum synovial tissues, especially in endothelial cells and macrophages. Moreover, the extent of pannus formation, which leads to bone destruction, is correlated with the content of vascular endothelial growth factor in the serum. There was no mortality in TM-treated rat abnormalities. TM also suppressed inflammatory cachexia. We suggest that copper deficiency induced by TM is a potent approach both to inhibit the progression of rheumatoid arthritis with minimal adverse effects and to improve the well-being of rheumatoid arthritis patients.
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DOI：
10.1073/pnas.1231994100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Mandinov, L;Mandinova, A;Maciag, T
通讯作者：
Maciag, T
影响因子：
7.1
作者：
HONKANEN, VEA;LAMBERG-ALLARDT, CH;KONTTINEN, YT
通讯作者：
KONTTINEN, YT
影响因子：
4.4
作者：
De Bandt, M;Ben Mahdi, MH;Pasquier, C
通讯作者：
Pasquier, C
影响因子：
2.9
作者：
Brewer, George J;Merajver, Sofia D
通讯作者：
Merajver, Sofia D
影响因子：
4.4
作者：
Matsumoto, Y;Tanaka, K;Iwamoto, Y
通讯作者：
Iwamoto, Y