Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy
Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy
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DOI：
10.1155/2013/565813
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Razdan, Rema
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文献类型：
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作者：
Bhadri, Naini;Sanji, Tejaswi;Razdan, Rema
顺铂或顺式二氨二氯铂（II）（CDDP）是一种细胞毒性化疗药物，具有剂量依赖性周围神经病变作为主要副作用，其特征为共济失调、疼痛和感觉障碍。已知CDDP的累积药物治疗会产生严重的氧化损伤。它主要靶向并积聚在背根神经节中，从而引起损伤，导致继发性神经纤维轴突病。在本研究中，我们研究了谷氨酸盐（MSG）与三种单独的抗氧化剂，即白藜芦醇，α-硫辛酸（ALA）和辅酶Q10（CoQ 10）的组合在顺铂（2 mg/kg，每周两次）诱导的大鼠周围神经病变中的神经保护作用。治疗8周后，通过测量行为和电生理特性和坐骨神经脂质过氧化以及谷胱甘肽和过氧化氢酶水平来确定神经保护的程度。结果表明，预先用MSG（500 mg/kg/d po）和白藜芦醇（10 mg/kg/d i. p.）或ALA（20 mg/kg/天i. p.）或CoQ 10（10 mg/kg每周三次i. p.）具有神经保护作用。在与白藜芦醇的组合中观察到MSG的最大神经保护作用。
Cisplatin or cis-diamminedichloroplatinum (II) (CDDP) is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG) with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA), and coenzyme Q10 (CoQ10), in cisplatin (2mg/kg i.p. twice weekly) induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po) with resveratrol (10 mg/kg/day i.p.) or ALA (20 mg/kg/day i.p.) or CoQ10 (10mg/kg weekly thrice i.p.) exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.