Alpha-lipoic acid and coenzyme Q10 combination ameliorates experimental diabetic neuropathy by modulating oxidative stress and apoptosis
Alpha-lipoic acid and coenzyme Q10 combination ameliorates experimental diabetic neuropathy by modulating oxidative stress and apoptosis
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DOI：
10.1016/j.lfs.2018.10.055
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发表时间：
2019-01-01
期刊：
影响因子：
6.1
通讯作者：
Hosseini, Asieh
中科院分区：
文献类型：
--
作者：
Galeshkalami, Nasrin Sadeghiyan;Abdollahi, Mohammad;Hosseini, Asieh
目的：糖尿病神经病变（DN）是糖尿病最常见的并发症。 α-硫辛酸 (ALA) 和辅酶 Q10 (CoQ10) 的神经保护作用此前已在 DN 中得到证实，但其潜在机制尚未确切被发现。本研究探讨了ALA和Q10组合通过改善氧化应激和细胞凋亡对实验性DN的神经保护作用。主要方法：我们研究了CoQ10（10 mg/kg，口服，五周）和/或ALA（100 mg/kg，口服，五周）对STZ（45 mg/kg，腹腔注射）诱导的大鼠DN的作用。治疗后通过开放场、生化和 ELISA 方法以及蛋白质印迹分析评估运动功能、氧化应激生物标志物、ATP 水平、caspase 3 和 UCP2 蛋白的表达。使用 H&E 染色方法对背根神经节 (DRG) 神经元进行组织学检查。主要发现：ALA 和/或 CoQ10 治疗通过调节移动距离和速度，显着 (p < 0.05) 减轻 DN 引起的运动功能缺陷。 ALA 和/或 CoQ10 治疗可显着抑制 DN 诱导的氧化应激，氧化应激与 DRG 神经元中 LPO 和 ROS 的减少以及 GSH 和 TAC 的增加有关。 ALA 和/或 CoQ10 被证明可以防止 DRG 神经元的凋亡和变性，这似乎是通过调节 caspase 3 和 UCP2 蛋白的表达、诱导 ATP 和改善 DN 诱导的 DRG 神经元变化来介导的。我们发现 ALA 和 CoQ10 组合对上述因素具有最大功效。意义：这些结果为 ALA 和 CoQ10 组合治疗 DN 的潜在机制提供了可能的基础。
Aims: Diabetic neuropathy (DN) is the most common complication of diabetes. Neuroprotective effects of alpha lipoic acid (ALA) and coenzyme Q10 (CoQ10) has been previously shown in DN, but underlying mechanisms involved not been exactly found. The present study explored the neuroprotective effects of ALA and Q10 combination in experimental DN by ameliorating oxidative stress and apoptosis.Main methods: We investigated the effects of CoQ10 (10 mg/kg, orally, five weeks) and/or ALA (100 mg/kg, orally, five weeks) in STZ (45 mg/kg, i.p.)-induced DN in rats. After treatments motor function, oxidative stress biomarkers, ATP levels, expression of caspase 3 and UCP2 proteins were assessed by open-field, biochemical and ELISA methods and Western blot analysis. Dorsal root ganglion (DRG) neurons were histologically examined using H&E staining method.Key findings: ALA and/or CoQ10 treatment significantly (p < 0.05) attenuated DN - induced motor function deficiency by modulating distance moved and velocity. ALA and/or CoQ10 treatment dramatically suppressed DN -induced oxidative stress which was associated with decrease in LPO and ROS and increase in GSH and TAC in DRG neurons. ALA and/or CoQ10 was proved to prevent apoptosis and degeneration of DRG neurons, which appears to be mediated by regulating the expression of caspase 3 and UCP2 proteins, inducing ATP and improving DN-induced changes in DRG neurons. We found maximum effectiveness with ALA and CoQ10 combination on mentioned factors.Significance: These results provide a possible basis of the underlying mechanism for application of ALA and CoQ10 combination in treatment of DN.