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The Effect of 3-Hydroxypyridine and Succinic Acid Derivatives on the Activity of Monoamine Oxidases in the Brain Cortex of Rats with Alloxan-Induced Diabetes

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Abstract—We studied the effects of original Russian 3-hydroxypyridine and succinic acid derivatives (emoxypine, reamberin, and mexidol) on the dynamics of activity of monoamine oxidases (МАО-А and МАО-B) and correlated them to the levels of biogenic amines (serotonin and dopamine) in the brain cortex during the first 2 weeks of alloxan-induced diabetes in rats. An injection of 3-hydroxypyridine derivatives for 7 or 14 days (emoxypine and mexidol) to the alloxan-induced diabetic rats at doses that are equivalent to the treatment range in humans prevented an increase in the activity of cortical МАО-А and dopamine deficiency. The strengths of the effects of emoxypine and mexidol were comparable to the effect of the reference agent α‑lipoic acid. The isolated succinic acid derivative (reamberin) attenuated the activity of МАО-А in the neocortex of rats with alloxan-induced diabetes but caused a transient decrease in cortical serotonin and dopamine levels at the early stages of experiments and failed to correct dopamine deficiency by the end of experiments. A course of injection of the studied drugs for 7 and 14 days increased cortical МАО-B activity; this increase was not associated with a parallel shifts in monoamine levels in the brain cortex of rats with alloxan diabetes. The changes in the activity of cortical МАО that were induced by the drugs were not associated with their effect on the level of circulating corticosterone and hyperglycemia in rats with alloxan-induced diabetes.

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Funding

This study was performed within the framework of the State Task on Research and Development Pharmacophysiology and Biochemical Pharmacology of 3-Hydroxypyridine and Succinic Acid Derivatives (State Registration: АААА-А18-118021890008-4. Registration date: February 18, 2018).

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Authors and Affiliations

  1. South Ural State Medical University, ul. Vorovskogo 64, 454092, Chelyabinsk, Russia

    I. A. Volchegorskii, A. I. Sinitskii, I. Yu. Miroshnichenko & L. M. Rassokhina

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  1. I. A. Volchegorskii
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  2. A. I. Sinitskii
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  3. I. Yu. Miroshnichenko
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  4. L. M. Rassokhina
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Correspondence to I. A. Volchegorskii.

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Conflict of interest. The authors declared no conflicts of interest.

Ethical approval. This study was performed in compliance with the Russian and International Ethical Principles and Guidelines for Experiments with Animals [22].

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Volchegorskii, I.A., Sinitskii, A.I., Miroshnichenko, I.Y. et al. The Effect of 3-Hydroxypyridine and Succinic Acid Derivatives on the Activity of Monoamine Oxidases in the Brain Cortex of Rats with Alloxan-Induced Diabetes. Neurochem. J. 13, 256–267 (2019). https://doi.org/10.1134/S1819712419020132

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