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The protective effects of sumatriptan on vincristine - induced peripheral neuropathy in a rat model
NeuroToxicology ( IF 3.4 ) Pub Date : 2018-06-26 , DOI: 10.1016/j.neuro.2018.06.012
Mina Khalilzadeh , Ghodratollah Panahi , Amir Rashidian , Mohammad Reza Hadian , Alireza Abdollahi , Khashayar Afshari , Saeed Shakiba , Abbas Norouzi-Javidan , Nastaran Rahimi , Majid Momeny , Ahmad Reza Dehpour

Clinical use of vincristine (VCR), an effective chemotherapeutic agent, has been limited due to its peripheral neuropathy toxicity. Sumatriptan, which is an anti-migraine agent is a specific agonist for 5-hydroxytryptamine 1B, 1D (5HT1B, 1D) receptors. Several studies have shown that sumatriptan exerts anti-inflammatory and immunomodulatory properties. This study aimed to investigate the effects of sumatriptan on VCR-induced peripheral neuropathy in a rat model. Male Wistar rats were intraperitoneally injected with VCR and normal saline four times per week for 2 weeks. In the treatment group, sumatriptan (1 mg/kg) was administered intraperitoneally 30 min prior to VCR injection every day. Mortality rate, weight variations and histopathological changes were monitored. Hot plate, tail flick and motor nerve conduction velocity (MNCV) tests were used to evaluate sensory and motor neuropathy. Levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and caspase-3 in the dorsal ganglion root were assessed by quantitative reverse transcription-PCR (qRT-PCR). Moreover, the protein levels of p65 nuclear factor kappa B (NF-<kappa > B) and phospho-p65 NF-<kappa > B were examined by Western blot analysis. Co-administration of sumatriptan with VCR significantly reversed alterations in the hot plate, tail flick threshold and sciatic MNCV induced by VCR and also prevented mixed sensory-motor neuropathy, as indicated by better general conditions, behavioral and electrophysiological results. In addition, sumatriptan improved the body weight loss caused by VCR. The mRNA levels of TNF-α, IL-1β and caspase-3 were significantly diminished in the treatment group. These findings were confirmed by histopathological analysis. In conclusion, this study demonstrated that sumatriptan significantly attenuated VCR-induced neuropathy and could be considered as a neuroprotective agent to prevent the VCR-induced neuropathy.



中文翻译:

舒马普坦对长春新碱诱发的大鼠周围神经病变的保护作用。

长春新碱(VCR)是一种有效的化疗药物,由于其周围神经病变毒性而受到临床限制。舒马曲坦是一种抗偏头痛药物,是5-羟基色胺1B,1D(5HT1B,1D)受体的特异性激动剂。几项研究表明舒马曲坦具有抗炎和免疫调节作用。这项研究旨在调查舒马普坦对VCR诱发的大鼠模型周围神经病变的影响。每周四次给雄性Wistar大鼠腹腔注射VCR和生理盐水,持续2周。在治疗组中,每天VCR注射前30分钟腹膜内给予舒马普坦(1 mg / kg)。监测死亡率,体重变化和组织病理学变化。热板 甩尾和运动神经传导速度(MNCV)测试用于评估感觉和运动神经病。通过定量逆转录PCR(qRT-PCR)评估背神经节根中的肿瘤坏死因子-α(TNF-α),白介素-1β(IL-1β)和胱天蛋白酶-3的水平。此外,通过蛋白质印迹分析检查了p65核因子κB(NF-κb)和磷酸-p65NF-κB的蛋白水平。舒马曲坦与VCR的共同给药可显着逆转VCR引起的热板改变,甩尾阈和坐骨神经MNCV改变,并且还可以预防混合的感觉运动神经病,如更好的一般条件,行为和电生理结果所表明的。此外,舒马曲坦改善了VCR引起的体重减轻。TNF-α的mRNA水平 治疗组中IL-1β和caspase-3显着降低。这些发现已通过组织病理学分析证实。总之,这项研究表明舒马普坦显着减轻了VCR引起的神经病,可以被认为是预防VCR引起的神经病的神经保护剂。

更新日期:2018-06-26
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