Antioxidative and Anti-Inflammatory Potentials of Ambroxol in Ameliorating Vincristine Induced Peripheral Neuropathic Pain in Rats

Bhardwaj Hc, A. Muthuraman, Hari Ksl, S. Navis
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引用次数: 8

Abstract

The present study was designed to investigate the ameliorative potential of Ambroxol, a voltage gated sodium channel 1.8 (VGSC 1.8) inhibitor in Vincristine induced neuropathic pain in rats. Administration with Vincristine (75 μg/mg, intraperitoneal) for 10 consecutive days induces neuropathic pain. Hyperalgesia and allodynic symptoms were assessed with various behavioral models i.e., paw thermal-heat hyperalgesia, tail cold hyperalgesia and paw cold allodynia via hot-plate test, cold-water tail immersion test and acetone drop test at different time intervals of 0,1,7,14, and 21 days. Oxidative stress markers i.e., thio-barbituric acid reactive substances, superoxide anion content and inflammatory mediators like tumor necrosis factor-alpha and myeloperoxidase were biochemically assessed from sciatic nerve tissue and surrounding muscular tissue homogenates respectively. Pharmacological cotreatments with Ambroxol (1000 mg/kg, per oral), Carbamazepine (100 mg/kg, per oral) and combination of Ambroxol with Pregabalin (10 mg/kg, per oral) for 14 days, significantly ameliorate the Vincristine induced neuropathic pain in terms of attenuating paw thermal hyperalgesia, tail-cold hyperalgesia and paw cold allodynia along with decrease in oxidative stress markers and inflammatory mediators. Therefore, on the basis of data in hand from present study, it has been concluded that Ambroxol have neuroprotective potential in ameliorating Vincristine induced neuropathic pain in rats.
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氨溴索对长春新碱诱导的大鼠周围神经性疼痛的抗氧化和抗炎作用
本研究旨在探讨电压门控钠通道1.8 (VGSC 1.8)抑制剂氨溴索对长春新碱诱导的大鼠神经性疼痛的改善潜力。长春新碱(75 μg/mg,腹腔注射)连续10天可引起神经性疼痛。在0、1、7、14、21 d的不同时间间隔内,采用热板试验、冷水尾浸泡试验、丙酮滴试验等不同的行为学模型,对大鼠爪热-热痛觉过敏、尾冷痛觉过敏、爪冷异痛觉症状进行评估。分别从坐骨神经组织和周围肌肉组织匀浆中生化评估氧化应激标志物,即硫代巴比妥酸反应性物质、超氧阴离子含量和炎症介质,如肿瘤坏死因子- α和髓过氧化物酶。氨溴索(1000 mg/kg,每次口服)、卡马西平(100 mg/kg,每次口服)联合氨溴索与普瑞巴林(10 mg/kg,每次口服)治疗14天,显著改善了长春新碱引起的神经性疼痛,减轻了脚爪热痛症、尾冷痛症和脚爪冷异常性疼痛,同时降低了氧化应激标志物和炎症介质。因此,根据本研究的数据,我们认为氨溴索对长春新碱引起的大鼠神经性疼痛具有神经保护作用。
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