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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

  • T. M. KuchmerovskaEmail author
  • K. O. Dyakun
  • M. M. Guzyk
  • L. V. Yanytska
  • I. B. Pryvrotska
Article
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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.

Keywords

diabetes oxidative stress acetyl-L-carnitine alpha-lipoic acid nicotinamide CYP2E1 mitochondria membrane potential synaptic membranes ATP NAD+ 

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • T. M. Kuchmerovska
    • 1
    Email author
  • K. O. Dyakun
    • 1
  • M. M. Guzyk
    • 1
  • L. V. Yanytska
    • 2
  • I. B. Pryvrotska
    • 3
  1. 1.Palladin Institute of Biochemistry, NAS of UkraineKyivUkraine
  2. 2.Bogomolets National Medical University, Ministry of Public Health of UkraineKyivUkraine
  3. 3.Gorbachevsky Ternopil’ State Medical University, Ministry of Public Health of UkraineTernopilUkraine

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