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The Effect of 3-Hydroxypyridine and Succinic Acid Derivatives on Hippocampal Monoamine Oxidase Activity in Rats with Alloxan-Induced Diabetes

  • Comparative and Ontogenic Biochemistry
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Abstract

The effect of the original, domestically manufactured, derivatives of 3-hydroxypyridine and succinic acid (emoxipine, reamberin and mexidol) on the dynamics of monoamine oxidase (MAO-A and MAO-B) activity was studied as compared with the hippocampal level of biogenic amines (serotonin and dopamine) during the first two weeks of alloxan-induced diabetes in rats. It was shown that during this period the hippocampus develops a buildup of dopamine and serotonin against the background of unchanged MAO-A and MAO-B activities. It was established that a 14-day administration of emoxipine, reamberin and mexidol in animals with alloxan-induced DM at doses equivalent to the human therapeutic range prevented an increase in paleocortical serotonin and dopamine levels. Succinate-containing drugs (reamberin and mexidol) induced a parallel decrease in the MAO-B activity in the Ammon’s horn of diabetic animals. Mexidol, which is a co-derivative of 3-hydroxypyridine and succinic acid, induced additionally decreased the hippocampal MAO-A activity. In terms of the severity of the above effects, reamberin and mexidol were not inferior to α-lipoic acid which was used as a reference drug. An isolated derivative of 3-hydroxypyridine (emoxipine), in contrast to reamberin, mexidol and α-lipoic acid, promoted normalization of paleocortical serotonin and dopamine levels but did not affect hippocampal MAO-A and MAO-B activities in rats with alloxan-induced DM. 3-hydroxypyridine derivatives (emoxipine and mexidol), in contrast to reamberin and α-lipoic acid, induced no transient increase in MAO activity and monoamine levels in the hippocampus of diabetic rats. These results are consistent with the previously demonstrated superiority of emoxipine and mexidol over reamberin and α-lipoic acid in the intensity of their cerebroprotective effects in alloxan-induced DM.

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Funding

This work was implemented within a state assignment “Pharmacophysiology and biochemi cal pharmacology of 3-oxypyridine and succinic acid derivatives” (reg. no. AAAA-A18-118021890008-4 of February 18, 2018).

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Authors and Affiliations

  1. South Ural State Medical University, 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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All applicable international, national and institutional principles of handling and using experimental animals for scientific purposes were observed. This study did not involve human subjects as research objects.

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Russian Text © The Author(s), 2020, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2020, Vol. 56, No. 1, pp. 13–23.

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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 Hippocampal Monoamine Oxidase Activity in Rats with Alloxan-Induced Diabetes. J Evol Biochem Phys 56, 11–21 (2020). https://doi.org/10.1134/S0022093020010020

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