{"title":"Dimethyl Fumarate Ameliorates Collagen-Induced Arthritis in Lewis Rats by Modulation of Th17/Treg Balance","authors":"Ali Sheikhian, Parisa Zafari, Mozhgan Faraji Talooki, Mahnaz Babaahmadi, Behnoosh Tayebi, Alimohammad Varzi, Alireza Rafiei","doi":"10.1002/jbt.70345","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects approximately 1% of the world's population. Due to its anti-inflammatory effects, Dimethyl fumarate (DMF) can be used to treat RA. However, its molecular mechanisms have not yet been fully elucidated. In this study, an animal model of collagen-induced arthritis (CIA) was used to investigate DMF's In Vivo effects and probable mechanism of action on arthritis.</p>\n <p>Twenty-five rats were divided into five groups: healthy control group (normal), CIA rats without any treatment (CIA control), CIA rats treated with vehicle, CIA rats treated with methotrexate (MTX), and CIA rats treated with DMF. Hind paw swelling and arthritis score were measured to evaluate DMF effects on the disease progression. Rats were killed on day 28; the plasma levels of IL-17, IL-10, and anti-collagen type II (CII) were measured by the ELISA method, and the percentage of Th17 and Treg cells in different groups was determined by flow cytometry.</p>\n <p>DMF significantly reduced the arthritis score, hind paw swelling, cartilage destruction, and joint inflammation in CIA rats. The level of CII and IL-17 was also lower in the DMF-treated group compared to the untreated group. The level of IL-10 was higher in the DMF-treated rats. Furthermore, the percentage of Th17 was lower, and the percentage of Treg was higher in DMF-treated rats compared to the control group.</p>\n <p>DMF demonstrated anti-arthritic activity by reducing the arthritis score, hind paw swelling, cartilage destruction, joint inflammation, and modulation of Treg/Th17 cells. Therefore, DMF may be considered as a new therapeutic agent in RA.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70345","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects approximately 1% of the world's population. Due to its anti-inflammatory effects, Dimethyl fumarate (DMF) can be used to treat RA. However, its molecular mechanisms have not yet been fully elucidated. In this study, an animal model of collagen-induced arthritis (CIA) was used to investigate DMF's In Vivo effects and probable mechanism of action on arthritis.
Twenty-five rats were divided into five groups: healthy control group (normal), CIA rats without any treatment (CIA control), CIA rats treated with vehicle, CIA rats treated with methotrexate (MTX), and CIA rats treated with DMF. Hind paw swelling and arthritis score were measured to evaluate DMF effects on the disease progression. Rats were killed on day 28; the plasma levels of IL-17, IL-10, and anti-collagen type II (CII) were measured by the ELISA method, and the percentage of Th17 and Treg cells in different groups was determined by flow cytometry.
DMF significantly reduced the arthritis score, hind paw swelling, cartilage destruction, and joint inflammation in CIA rats. The level of CII and IL-17 was also lower in the DMF-treated group compared to the untreated group. The level of IL-10 was higher in the DMF-treated rats. Furthermore, the percentage of Th17 was lower, and the percentage of Treg was higher in DMF-treated rats compared to the control group.
DMF demonstrated anti-arthritic activity by reducing the arthritis score, hind paw swelling, cartilage destruction, joint inflammation, and modulation of Treg/Th17 cells. Therefore, DMF may be considered as a new therapeutic agent in RA.
类风湿性关节炎（RA）是一种慢性炎症性自身免疫性疾病，影响着世界上大约1%的人口。由于其抗炎作用，富马酸二甲酯（DMF）可用于治疗类风湿性关节炎。然而，其分子机制尚未完全阐明。本研究采用胶原诱导关节炎（CIA）动物模型，探讨DMF对关节炎的体内作用及其可能的作用机制。将25只大鼠分为5组：健康对照组（正常）、未处理CIA大鼠（CIA对照组）、载药组、甲氨蝶呤（MTX）组、DMF组。测量后爪肿胀和关节炎评分以评估DMF对疾病进展的影响。第28天处死大鼠；ELISA法检测各组血清IL-17、IL-10、抗ⅱ型胶原（anti-collagen type II， CII）水平，流式细胞术检测各组血清Th17、Treg细胞百分比。DMF显著降低CIA大鼠关节炎评分、后爪肿胀、软骨破坏和关节炎症。dmf治疗组的CII和IL-17水平也低于未治疗组。dmf处理大鼠IL-10水平升高。此外，与对照组相比，dmf处理大鼠的Th17百分比较低，Treg百分比较高。DMF通过降低关节炎评分、后肢肿胀、软骨破坏、关节炎症和调节Treg/Th17细胞显示出抗关节炎活性。因此，DMF可能被认为是一种新的RA治疗药物。
期刊介绍：
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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