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三氧化二砷治疗红斑狼疮的潜力。

The Potential Use of Arsenic Trioxide in the Treatment of Systemic Lupus Erythematosus.

机构信息

Department of Medicine, Ruttonjee Hospital, Hong Kong SAR, China.

Department of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong SAR, China.

出版信息

Int J Mol Sci. 2024 Sep 4;25(17):9577. doi: 10.3390/ijms25179577.

Abstract

Arsenic trioxide (ATO) is now part of the standard regimen for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia. The availability of an oral form of ATO has greatly reduced the incidence of cardiotoxicity as compared to intravenous (IV) administration. Increasing evidence suggests that ATO has anti-inflammatory properties that may be useful for the treatment of autoimmune diseases. These include the modulation of Treg cell activation, Th1/Th2 and Th17/Treg balance, depletion of activated T cells and plasmacytoid dendritic cells, and influence of B-cell differentiation, leading to reduced autoantibody and cytokine production. ATO has also been shown to induce apoptosis of activated fibroblast-like synoviocytes through the generation of reactive oxygen species and alter the gut microbiota in collagen-induced arthritis. Despite the emergence of newer treatment modalities, the treatment of systemic lupus erythematosus (SLE), especially refractory manifestations, remains a challenge, owing to the paucity of effective biological and targeted therapies that are devoid of adverse effects. Oral ATO is an attractive option for the treatment of SLE because of the lower cost of production, convenience of administration, and reduced cardiotoxicity. This article summarizes the anti-inflammatory mechanisms of ATO and its potential application in the treatment of SLE and other rheumatic diseases.

摘要

三氧化二砷(ATO)现已成为治疗新诊断和复发的急性早幼粒细胞白血病的标准方案的一部分。与静脉注射(IV)相比,ATO 口服剂型的出现大大降低了心脏毒性的发生率。越来越多的证据表明,ATO 具有抗炎特性,可用于治疗自身免疫性疾病。这些特性包括调节 Treg 细胞激活、Th1/Th2 和 Th17/Treg 平衡、耗竭活化的 T 细胞和浆细胞样树突状细胞,以及影响 B 细胞分化,从而减少自身抗体和细胞因子的产生。ATO 还通过产生活性氧诱导活化的成纤维样滑膜细胞凋亡,并改变胶原诱导性关节炎中的肠道微生物群。尽管出现了更新的治疗方式,但由于缺乏有效且无不良反应的生物制剂和靶向治疗药物,治疗系统性红斑狼疮(SLE),特别是难治性表现,仍然是一个挑战。口服 ATO 是治疗 SLE 的一种有吸引力的选择,因为生产成本较低、给药方便且心脏毒性降低。本文总结了 ATO 的抗炎机制及其在治疗 SLE 和其他风湿性疾病中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/676b/11394723/1b08b04f5c7b/ijms-25-09577-g001.jpg

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