Diacerein reduces sensorimotor deficits after spinal cord injury by clip-compression in female rats by protection of cellular damage in long time

Fernando da Silva Fiorin , Douglas Buchmann Godinho , Rafael Parcianello Cipolat , Luiz Fernando Freire Royes , Caroline Cunha do Espírito Santo
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Abstract

Spinal cord injury (SCI) is a cause of long-term disability, and one of the main problems is sensorimotor response impairment. Thus, become important treatments that reduce the progressive secondary damage that causes the loss of spared neurons. Due to the oxidative stress and inflammation interaction after damage, we tested if diacerein, a classic pharmacologic anti-inflammatory, could reduce the cell damage in the long term and recover sensorimotor responses after SCI in rats. Clip-compression SCI model in female Wistar rats caused severe locomotory loss performance showed through assessment by the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and induced thermal hyperalgesia observed by Plantar Test Apparatus. When diacerein was administered twice a day for thirty-five days, the data presented a significant recovery of locomotion and an attenuation of thermal hyperalgesia. The increased adrenal glands’ weight and reduced soleus muscle mass were attenuated by diacerein. The immunoblotting showed that diacerein prevented progressive damage at the site of injury demonstrated by the recovery of nuclear factor erythroid-2 related factor 2 (Nrf2) levels, reduction of protein nitration by 3-nitrotyrosine (3-NT) expression and inflammation decreased showed by a less expression in glial fibrillary acidic protein (GFAP) immune content induced by injury. Therefore, the present data suggest that blockage of secondary damage by diacerein can inhibit the oxidative/inflammatory process by increasing Nrf2 and improving sensorimotor recovery in rats.

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双醋瑞因通过长时间保护细胞损伤,减少雌性大鼠脊髓夹压损伤后的感觉运动障碍
脊髓损伤(SCI)是导致长期残疾的原因之一,其中一个主要问题是感觉运动反应障碍。因此,减少导致幸免神经元丧失的渐进性继发性损伤的治疗方法变得非常重要。由于损伤后氧化应激和炎症相互作用,我们测试了经典的药理抗炎药物 diacerein 是否能长期减少细胞损伤并恢复大鼠 SCI 后的感觉运动反应。通过巴索、比提和布雷斯纳汉(BBB)运动评分量表的评估,雌性 Wistar 大鼠的夹压 SCI 模型导致了严重的运动机能丧失,并通过足底试验器械观察到诱发热痛。在连续三十五天每天两次服用迪卡瑞林的情况下,数据显示运动能力显著恢复,热痛感也有所减轻。肾上腺重量的增加和比目鱼肌质量的减少在迪卡瑞林的作用下得到了缓解。免疫印迹显示,迪卡瑞林可防止损伤部位的渐进性损伤,具体表现在核因子红细胞-2相关因子2(Nrf2)水平的恢复、3-硝基酪氨酸(3-NT)蛋白硝化表达的减少以及损伤引起的神经胶质纤维酸性蛋白(GFAP)免疫成分表达的减少。因此,本研究数据表明,迪卡西林可以通过增加 Nrf2 抑制氧化/炎症过程,改善大鼠的感觉运动恢复。
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