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Effects of a Combined Mitochondria-Targeted Treatment on the State of Mitochondria and Synaptic Membranes from the Brains of Diabetic Rats
Neurophysiology ( IF 0.5 ) Pub Date : 2019-12-04 , DOI: 10.1007/s11062-019-09816-6
T. M. Kuchmerovska , K. O. Dyakun , M. M. Guzyk , L. V. Yanytska , I. B. Pryvrotska

On samples of the mitochondria and synaptic membranes isolated from rat brains using differential centrifugation, we tried to evaluate the neuroprotective efficacy of a combination of mitochondriaspecific antioxidants, acetyl-L-carnitine (ALC) and α-lipoic acid (LA), with nicotinamide (NAm), against diabetes-induced disorders in the CNS. Three groups of adult male Wistar rats were examined; these were control intact rats (group C), animals with experimental streptozotocin (STZ)-induced diabetes (group D; 6 weeks after STZ injections), and diabetic rats treated during the two final weeks of the above period by a combination of ALC, LA, and NAm (separate daily injections; doses 100, 50, and 100 mg/kg body mass, respectively; group D+T). At the day of preparation of the organelle samples, the mean blood glucose levels in groups C, D, and D+T were 4.8, 20.3, and 15.4 mM, respectively. The intensity of reactive oxygen species (ROS) production in the brain mitochondria from rats of group D measured by fluorescent analyses using 2’,7’-dichlorofluorescein diacetate was, on average, 37.2% greater than that in group C. Co-treatment provided a significant decrease in the above index in group D+T (27.8% in comparison with group D). Diabetes led to dramatic intensification of the CYP2E1 protein level in the liver of group D animals (242% vs. group C). In group D+T, this index was 33.1% lower than that in group D.

中文翻译:

联合线粒体靶向治疗对糖尿病大鼠脑线粒体和突触膜状态的影响

在使用差速离心法从大鼠脑中分离的线粒体和突触膜样本上,我们试图评估线粒体特异性抗氧化剂乙酰-L-肉碱 (ALC) 和α-硫辛酸 (LA) 与烟酰胺的组合的神经保护功效。 NAm),对抗糖尿病引起的中枢神经系统疾病。检查了三组成年雄性 Wistar 大鼠;这些是对照完整大鼠(C 组)、实验性链脲佐菌素(STZ)诱导的糖尿病动物(D 组;STZ 注射后 6 周),以及在上述时期的最后两周期间通过 ALC 组合治疗的糖尿病大鼠, LA 和 NAm(每日单独注射;剂量分别为 100、50 和 100 mg/kg 体重;D+T 组)。在细胞器样品制备当天,C、D和D+T组的平均血糖水平为4.8,分别为 20.3 和 15.4 mM。使用 2',7'-二氯荧光素二乙酸酯通过荧光分析测量 D 组大鼠脑线粒体中活性氧 (ROS) 产生的强度平均比 C 组高 37.2%。 D+T组上述指标显着下降(与D组相比27.8%)。糖尿病导致 D 组动物肝脏中 CYP2E1 蛋白水平的显着升高(242% 对 C 组)。D+T组该指标较D组低33.1%。联合治疗使 D+T 组的上述指标显着降低(与 D 组相比为 27.8%)。糖尿病导致 D 组动物肝脏中 CYP2E1 蛋白水平的显着升高(242% 对 C 组)。D+T组该指标较D组低33.1%。联合治疗使 D+T 组的上述指标显着降低(与 D 组相比为 27.8%)。糖尿病导致 D 组动物肝脏中 CYP2E1 蛋白水平的显着升高(242% 对 C 组)。D+T组该指标较D组低33.1%。
更新日期:2019-12-04
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