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Effect of 3-Oxypyridine Derivatives and Succinic Acid on the Activity of Monoamine Oxidases and the Content of Monoamines in the Hypothalamus of Rats with Alloxan-Induced Diabetes

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Abstract—We studied the effect of novel domestic derivatives of 3-oxypyridine and succinic acid (emoxypine, reamberin, and mexidol) on the activity of monoamine oxidases (MAO-A and MAO-B) and the level of biogenic amines (serotonin and dopamine) in the hypothalamus during the first two weeks of alloxan-induced diabetes in rats. During the first 14 days of alloxan-induced diabetes in rats, the levels of serotonin and dopamine decreased in the hypothalamus in the presence of unchanged MAO-B activity. The MAO-A activity and serotonin level in the hypothalamus of diabetic rats did not differ from the control values ​​at the initial stage of the experiment, and after a significant transient decrease, they again reached normal levels. The dopamine level in the hypothalamus of rats with experimental diabetes decreased only at the end of the experiment. The application of the studied drugs at doses equivalent to the therapeutic range for humans corrected the transient shifts in MAO-A activity and the delayed deficiency of monoamines in the hypothalamus of animals with alloxan-induced diabetes. The seven-day administration of an isolated derivative of 3-oxypyridine (emoxypine) and an isolated derivative of succinic acid (reamberin) prevented the transient decrease in MAO-A activity, compensated the concomitant deficiency of serotonin and increased the dopamine level in the hypothalamus of rats with alloxan-induced diabetes. Mexidol, which is simultaneously a derivative of 3‑oxypyridine and succinic acid, prevented a decrease in the hypothalamic levels of serotonin and dopamine in diabetic rats after 7 and 14-fold use (respectively). Correction of hypothalamic serotonin deficiency by Mexidol was not accompanied by changes in the activity of MAO-A and MAO-B. A decrease in hypothalamic dopamine deficiency as a result of a two-week administration of Mexidol was accompanied by a decrease in MAO-A activity. The intensity of neurochemical effects induced by derivatives of 3-oxypyridine and succinic acid were similar to α-lipoic acid which was used as a comparison drug.

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Funding

This study was performed as part of the state order “Pharmacophysiology and Biochemical Pharmacology of Derivatives of 3-Oxypyridine and Succinic Acid” (State registration number: AAAA-A18-118021890008-4. Registration date: February 18, 2018).

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  1. South Ural State Medical University, Ministry of Health of the Russian Federation, 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 declare that they have no conflict of interest.

Ethical approval. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Volchegorskii, I.A., Sinitskii, A.I., Miroshnichenko, I.Y. et al. Effect of 3-Oxypyridine Derivatives and Succinic Acid on the Activity of Monoamine Oxidases and the Content of Monoamines in the Hypothalamus of Rats with Alloxan-Induced Diabetes. Neurochem. J. 14, 215–226 (2020). https://doi.org/10.1134/S1819712420010201

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