Rodrigues Thiago A, de Oliveira Freire Abner, Carvalho Heetor C O, Silva Gyl E B, Vasconcelos José W, Guerra Rosane N M, de Sousa Cartágenes Maria do Socorro, Garcia João B S
Centro de Ciências Biológicas e da Saúde, Universidade Federal do Maranhão, São Luís, Brazil.
Front Pharmacol. 2018 Sep 19;9:975. doi: 10.3389/fphar.2018.00975. eCollection 2018.
Strontium ranelate (SrRan) has the potential to interfere in the progression of osteoarthritis (OA), multifactorial disease associated with mechanical problems and articular inflammatory changes. This study aimed to test the effects of prophylactic and therapeutic use of SrRan on clinical parameters of pain, the inflammatory process, and degradation of the articular cartilage. This was an experimental study, using a model of knee OA induced by intra-articular injection of monoiodoacetate. Thirty Wistar rats were divided into five groups and treated as indicated: control, without intervention; prophylactic, received SrRan at a daily oral dose of 250 mg/kg for 28 days before OA induction; SrRan treatments, administered 250 or 500 mg/kg/day for 28 days after the induction; and model control, received saline solution after the induction. Behavioral tests (joint incapacity, mechanical hyperalgesia, tactile sensitivity, and forced ambulation), histological evaluation of articular cartilage, and determination of inflammatory cytokines in the synovial fluid (interleukin [IL]-6, IL-10, tumor necrosis factor [TNF]-α, and interferon [INF]-γ) were performed. Both prophylactic and therapeutic treatments improved the articular discomfort. A prophylactic dose of 500 mg/kg/day also improved mechanical hyperalgesia and the same dose was beneficial on tactile sensitivity. SrRan did not improve ambulation. Levels of IL-6, IL-10, TNF-α, and IFN-γ in SrRan-treated groups with OA were not significantly different compared with those in the normal control animals. The histopathological evaluation showed less articular damage in the SrRan-treated and control groups compared to the saline-treated group. The prophylactic and therapeutic administration of SrRan was associated with improved behavioral patterns of pain, especially joint discomfort. SrRan administration mitigated histological changes in the articular cartilage and reduced the inflammatory process, which beneficially reduced the progression of OA in the experimental model studied.
雷奈酸锶（SrRan）有可能干预骨关节炎（OA）的进展，OA是一种与机械问题和关节炎症变化相关的多因素疾病。本研究旨在测试预防性和治疗性使用SrRan对疼痛的临床参数、炎症过程以及关节软骨降解的影响。这是一项实验研究，采用关节内注射单碘乙酸诱导的膝OA模型。30只Wistar大鼠分为五组并按以下方式处理：对照组，不进行干预；预防组，在OA诱导前每日口服250 mg/kg SrRan，共28天；SrRan治疗组，诱导后给予250或500 mg/kg/天，共28天；模型对照组，诱导后给予生理盐水。进行了行为测试（关节功能障碍、机械性痛觉过敏、触觉敏感性和强迫行走）、关节软骨组织学评估以及滑液中炎性细胞因子（白细胞介素[IL]-6、IL-10、肿瘤坏死因子[TNF]-α和干扰素[INF]-γ）的测定。预防性和治疗性治疗均改善了关节不适。500 mg/kg/天的预防剂量还改善了机械性痛觉过敏，且相同剂量对触觉敏感性有益。SrRan未改善行走能力。与正常对照动物相比，OA的SrRan治疗组中IL-6、IL-10、TNF-α和IFN-γ的水平无显著差异。组织病理学评估显示，与生理盐水治疗组相比，SrRan治疗组和对照组的关节损伤较少。SrRan的预防性和治疗性给药与疼痛行为模式的改善相关，尤其是关节不适。SrRan给药减轻了关节软骨的组织学变化并减少了炎症过程，这有益地减少了所研究实验模型中OA的进展。
