Bhadri Naini, Sanji Tejaswi, Madakasira Guggilla Hariprasad, Razdan Rema
Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore, Karnataka-560027, India.
ScientificWorldJournal. 2013 Dec 30;2013:565813. doi: 10.1155/2013/565813. eCollection 2013.
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 (2 mg/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 (10 mg/kg weekly thrice i.p.) exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.
顺铂或顺二氨二氯铂(II)(CDDP)是一种细胞毒性化疗药物,其主要副作用是剂量依赖性周围神经病变,表现为共济失调、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,进而导致损伤,引发继发性神经纤维轴索性病变。在本研究中,我们调查了谷氨酸钠(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(CoQ10)联合使用,对顺铂(2mg/kg腹腔注射,每周两次)诱导的大鼠周围神经病变的神经保护作用。治疗8周后,通过测量行为和电生理特性、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程度。结果表明,MSG(500mg/kg/天口服)与白藜芦醇(10mg/kg/天腹腔注射)或ALA(20mg/kg/天腹腔注射)或CoQ10(10mg/kg每周三次腹腔注射)联合预处理具有神经保护作用。在与白藜芦醇联合使用时,观察到MSG的最大神经保护作用。