Synergistic Antiparkinsonian Effect of Flunarizine, Glibenclamide and B Vitamins in a Rat 6-Hydroxydopamine Model; The Role of Malondialdehyde

M. Sarookhani, H. Haghdoost-Yazdi, H. Piri, Nafiseh Rastgoo, Parham Tadayon
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Abstract

Background: The current study evaluated the effects of a combination of flunarizine (flu) a calcium channel blocker, glibenclamide (Glib), a KATP channels blocker and B vitamins (B com) on the behavioral symptoms of 6-hydroxydopamine (6-OHDA)-induced model of Parkinson disease to evaluate the synergistic antiparkinsonian effects of the drugs and supplements. Also the level of malondialdehyde (MDA) was measured in blood and brain suspensions to find probable neuroprotective mechanism of these materials. Methods: 6-OHDA was injected into striatum of rats by stereotaxic surgery. Pretreatment with flu, Glib and B com was started before the surgery and continued to three weeks after the surgery. Development and severity of Parkinson disease were evaluated by the conventional behavioral tests. MDA values were measured spectrophotometrically, using thiobarbituric acid test and the MDA standard curve. Results: Pretreatment with a combination of flu, Glib and B com ameliorated the behavioral symptoms of Parkinson disease. The effect of the combination was significantly more potent than those of flu, Glib or B com, solely. Pretreatment with the combination or using only Glib or B com separately, reduced the level of MDA in blood and brain, significantly. However, the effect of the combination was significantly more potent than those of Glib or B com, solely. Conclusions: Since the severity of the behavioral symptoms in the 6-OHDA-induced model of Parkinson disease reflects the degree of the lesion in substantia nigra (SN) dopaminergic neurons, it is suggested that using the combination had neuroprotective effects. The obtained data suggest a synergistic neuroprotective and antiparkinsonian effect for flu, Glib and B com. At least, a part of this effect was mediated through inhibition of oxidative stress. Keywords: 6-Hydroxydopamine, Flunarizine, Glibenclamide: B Vitamins, Behavioral Symptoms, Malondialdehyde
氟桂利嗪、格列本脲和B族维生素对6-羟多巴胺模型大鼠的协同抗帕金森病作用丙二醛的作用
背景:本研究评估了氟桂利嗪(flu)钙通道阻滞剂、格列本脲(Glib)、KATP通道阻滞剂和B族维生素(bcom)联合应用对6-羟多巴胺(6-OHDA)诱导的帕金森病模型行为症状的影响,以评价药物和补充剂的协同抗帕金森病作用。同时测定了血液和脑悬浮液中丙二醛(MDA)的水平,以发现这些物质可能的神经保护机制。方法:采用立体定向手术将6-羟色胺注入大鼠纹状体。手术前开始使用流感、Glib和bcom进行预处理,并持续到手术后三周。通过常规行为测试评估帕金森病的发展和严重程度。采用硫代巴比妥酸法和MDA标准曲线,分光光度法测定MDA值。结果:flu、Glib和bcom联合预处理可改善帕金森病的行为症状。两者联合使用的效果明显比单独使用流感病毒、Glib病毒或乙型肝炎病毒更有效。联合使用或单独使用Glib或B com预处理,可显著降低血液和脑内MDA水平。然而,联合使用的效果明显比单独使用Glib或b.com更有效。结论:6-羟多巴胺诱导的帕金森病模型行为症状的严重程度反映了黑质多巴胺能神经元的损伤程度,提示联合用药具有神经保护作用。获得的数据表明,对流感,Glib和bcom具有协同神经保护和抗帕金森作用。至少,这种效果的一部分是通过抑制氧化应激介导的。关键词:6-羟多巴胺,氟桂利嗪,格列本脲,B族维生素,行为症状,丙二醛
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