Department of Pathology, Faculty of Medicine, Fırat University, Elazığ, Turkey.
Department of Rheumatology, Faculty of Medicine, Fırat University, Elazığ, Turkey.
Turk J Med Sci. 2017 Jun 12;47(3):1037-1044. doi: 10.3906/sag-1606-80.
BACKGROUND/AIM: Gemcitabine (GEM) has antiproliferative effects on lymphocytes, which are potent pathogenic actors of rheumatoid arthritis (RA). The aim of the study was to investigate the therapeutic potential of GEM on collagen-induced arthritis (CIA).
Arthritis was induced by the intradermal injection of chicken type II collagen with incomplete Freund's adjuvant into albino Wistar rats. Doses of 5 and 20 mg/kg GEM were administered twice a week after the 14th day, which marked the onset the arthritis. Serum IL-17, TNF-α, malondialdehyde, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels and tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels were analyzed.
Histopathologically prevalent inflammation and cartilage/bone destruction were observed in the arthritis group. Moreover, in the arthritis group serum IL-17, TNF-α, and malondialdehyde levels were significantly increased while catalase, SOD, GPx, HO-1, and Nrf2 levels were significantly decreased. However, in the GEM-treated groups, decreased TNF-α, IL-17, and malondialdehyde levels; increased SOD, catalase, GPx, Nrf2, and HO-1 levels; and ameliorated perisynovial inflammation and cartilage/bone destruction were observed.
GEM suppresses cytokine levels and enhances antioxidant activity. It also prevents cartilage/bone destruction in the CIA model. GEM may be a viable candidate for research into the treatment of RA.
背景/目的:吉西他滨(GEM)对淋巴细胞具有抗增殖作用,而淋巴细胞是类风湿关节炎(RA)的致病因素。本研究旨在探讨 GEM 对胶原诱导性关节炎(CIA)的治疗潜力。
通过在白化 Wistar 大鼠皮内注射鸡 II 型胶原和不完全弗氏佐剂来诱导关节炎。在关节炎发病后的第 14 天开始,每周两次给予 GEM 剂量为 5 和 20mg/kg。分析血清白细胞介素 17(IL-17)、肿瘤坏死因子-α(TNF-α)、丙二醛、过氧化氢酶、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)水平以及组织血红素加氧酶-1(HO-1)和核因子红细胞 2 相关因子 2(Nrf2)水平。
关节炎组可见普遍炎症和软骨/骨破坏。此外,关节炎组血清中 IL-17、TNF-α 和丙二醛水平显著升高,而过氧化氢酶、SOD、GPx、HO-1 和 Nrf2 水平显著降低。然而,在 GEM 治疗组中,TNF-α、IL-17 和丙二醛水平降低,SOD、过氧化氢酶、GPx、Nrf2 和 HO-1 水平升高,并且观察到peri 滑膜炎症和软骨/骨破坏得到改善。
GEM 可抑制细胞因子水平,增强抗氧化活性,预防 CIA 模型中的软骨/骨破坏。GEM 可能是研究治疗 RA 的候选药物。