Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the joints. Although methotrexate (MX) is the first-line treatment, side effects are common. This study aimed to investigate the effects of quercetin (QT) and/or MX on inflammation and systemic toxicity in a rat model of RA. Male Wistar rats were divided into control (C), RA, QT, MX, and QT + MX groups (n=6). The RA induction consisted of three intra-articular injections of methylated bovine serum albumin (1×/week) in the temporomandibular joint (TMJ). QT (25 mg/kg) and/or MX (0.75 mg) administration occurred by oral gavage daily. We performed mechanical hyperalgesia in TMJ, leukocyte recruitment in synovial fluid, histopathology, and immunohistochemistry (TNF-α, IL-17, and IL-10) in synovial membrane and toxicity parameters. The RA showed a reduction in the nociceptive threshold (p<0.001), increase in leukocyte recruitment in synovial fluid (p<0.001), intense inflammatory infiltrate (p<0.001), and intense immunoexpression of TNF-α, IL-17, and IL-10 in the synovial membrane (p<0.001) compared to C (p<0.001). QT and/or MX therapy reduced inflammatory parameters (p<0.001). However, downregulation of IL-10 was observed only in the groups that received MX (p<0.001). Leukocytosis was seen in RA (p<0.05), but QT and/or MX reversed it (p<0.05). MX was associated with pathological changes in the liver and higher levels of transaminases when compared to the other groups (p<0.05). QT co-administered with MX reversed this hepatotoxicity (p<0.05). There were no alterations in the kidney between the groups (p>0.05). QT has potential to support MX therapy, showing anti-inflammatory and hepatoprotective effects in this model.

类风湿性关节炎（RA）是一种以关节炎症为特征的自身免疫性疾病。尽管甲氨蝶呤 (MX) 是一线治疗药物，但副作用很常见。本研究旨在调查槲皮素 (QT) 和/或 MX 对 RA 大鼠模型炎症和全身毒性的影响。雄性Wistar大鼠分为对照组（C）、RA、QT、MX和QT+MX组（n=6）。RA 诱导包括在颞下颌关节 (TMJ) 关节内注射 3 次甲基化牛血清白蛋白 (1 次/周)。QT (25 mg/kg) 和/或 MX (0.75 mg) 每天通过口服强饲法给药。我们对 TMJ 进行了机械性痛觉过敏、滑液中的白细胞募集、组织病理学和滑膜中的免疫组织化学（TNF-α、IL-17 和 IL-10）和毒性参数。RA 显示伤害性阈值降低 ( p <0.001)，滑液中白细胞募集增加 ( p <0.001)，炎症浸润强烈 ( p <0.001)，TNF-α、IL-17 和滑膜中的 IL-10 ( p <0.001) 与 C ( p<0.001)。QT 和/或 MX 治疗降低了炎症参数 ( p <0.001)。然而，仅在接受 MX 的组中观察到 IL-10 的下调（p <0.001）。RA 可见白细胞增多（p <0.05），但 QT 和/或 MX 可逆转（p <0.05）。与其他组相比，MX 与肝脏的病理变化和更高水平的转氨酶有关（p <0.05）。QT 与 MX 共同给药可逆转这种肝毒性 ( p <0.05)。各组间肾脏无明显改变（p >0.05）。QT 具有支持 MX 治疗的潜力，在该模型中显示出抗炎和保肝作用。