Experimental substantiation of the expediency of the combined use of piracetam and metformin for pharmacological correction of cognitive disorders in conditions of prolonged hyperglycemia

Authors

DOI:

https://doi.org/10.26641/2307-0404.2020.3.214647

Keywords:

alloxan-induced hyperglycemia, diabetic encephalopathy, cognitive deficit, metformin, piracetam

Abstract

Chronic hyperglycemia, insulin resistance, endothelial dysfunction, and disturbance of the integrity of the blood-brain barrier are considered as strategically important links in the development of cognitive deficits in diabetic encephalopathy. Taking this into account, one of the modern trends in the optimization of the treatment of cognitive impairments induced by prolonged hyperglycemia is the co-administration of agents with antihyperglycemic and nootropic activity, in particular, metformin with piracetam. It has been shown that under conditions of experimental alloxan-induced hyperglycemia, piracetam has insufficient nootropic potential for eliminating cognitive deficits. Metformin has a weak nootropic effect in short-term use in low doses, without exhibiting these properties in prolonged administration. When combined with piracetam, metformin potentiates its antiamnesic properties, which helps to restore cognitive functions impaired by hyperglycemia. It is assumed that the mechanisms of such synergism are mediated by a decrease in the content of early and late markers of the destruction of protein molecules, the level of stable nitric oxide metabolites in the cerebral cortex, as well as a significant limitation of the manifestations of ultrastructural destructive changes in hippocampal neurons with a simultaneous improvement in the state of its microvasculature. The obtained results indicate the expediency of the combined use of metformin with nootropic agents for the prevention or treatment of cognitive impairments that occur as a result of diabetes mellitus.

Author Biographies

А. E. Lievykh

SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine»
Department of Pharmacology and Clinical Pharmacology
V. Vernadsky str., 9, Dnipro, 49044, Ukraine

N. S. Bondarenko

SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine»
Department of Pharmacology and Clinical Pharmacology
V. Vernadsky str., 9, Dnipro, 49044, Ukraine

S. N. Dronov

SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine»
Department of Pharmacology and Clinical Pharmacology
V. Vernadsky str., 9, Dnipro, 49044, Ukraine

V. I. Mamchur

SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine»
Department of Pharmacology and Clinical Pharmacology
V. Vernadsky str., 9, Dnipro, 49044, Ukraine

I. V. Tverdokhlib

SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine»
Department of Pharmacology and Clinical Pharmacology
V. Vernadsky str., 9, Dnipro, 49044, Ukraine

V. I. Zhyliuk

SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine»
Department of Pharmacology and Clinical Pharmacology
V. Vernadsky str., 9, Dnipro, 49044, Ukraine

References

Antomonov MYu. [Mathematical processing and analysis of medical and biological data]. Kyiv: Malyi druk; 2006. p. 558. Russian.

Ostroumova OD, Surkova EV, Chikh EV, Rebrova EV, Borisov MS. [Cognitive impairment in patients with type 2 diabetes mellitus: prevalence, pathogenetic mechanisms, the effect of antidiabetic drugs]. Sakharnyi diabet. 2018;21(4):307-18. Russian. doi: https://doi.org/10.14341/DM9660

Chernobrivtsev OP, Zyablitsev SV, Panova TI. Panchenko YuO. [Endothelial dysfunction in type 2 diabetes. Review]. Medychna nauka Ukrainy. 2019;15(1-2):80-86. Ukrainian. doi:

Bako HY, Ibrahim MA, Isah MS, Ibrahim S. Inhibition of JAK-STAT and NF-κB signalling systems could be a novel therapeutic target against insulin resistance and type 2 diabetes. Life Sci. 2019 Dec 15;239:117045. Epub 2019 Nov 12. PMID: 31730866. doi: https://doi.org/10.1016/j.lfs.2019.117045

Cui Y, Liang X, Gu H, Hu Y, Zhao Z, Yang XY, Qian C, Yang Y, Teng GJ. Cerebral perfusion alterations in type 2 diabetes and its relation to insulin resistance and cognitive dysfunction. Brain Imaging Behav. 2017 Oct;11(5):1248-57. PMID: 27714551. doi: https://doi.org/10.1007/s11682-016-9583-9

V Pinto R, Antunes F, Pires J, Silva-Herdade A, Pinto ML. A Comparison of Different Approaches to Quantify Nitric Oxide Release from NO-Releasing Materials in Relevant Biological Media. Molecules. 2020 Jun 2;25(11):2580. PMID: 32498254. doi: https://doi.org/10.3390/molecules25112580

Lin LW, Tsai FS, Yang WT, Lai SC, Shih CC, Lee SC, Wu CR. Differential change in cortical and hip­pocampal monoamines, and behavioral patterns in streptozotocin-induced type 1 diabetic rats. Iran J Basic Med Sci. 2018 Oct;21(10):1026-34. PMID: 30524676. PMCID: PMC6281071. doi: https://doi.org/10.22038/IJBMS.2018.29810.7197

Gambaryan S, Tsikas D. A review and discussion of platelet nitric oxide and nitric oxide synthase: do blood platelets produce nitric oxide from L-arginine or nitrite? Amino Acids. 2015 Sep;47(9):1779-93. Epub 2015 May 1. PMID: 25929585.

Hasanein P, Emamjomeh A, Chenarani N, Boh­looli M. Beneficial effects of rutin in diabetes-induced deficits in acquisition learning, retention memory and pain perception in rats. Nutr Neurosci. 2020 Jul;23(7):563-74. PMID: 30321127. doi: https://doi.org/10.1080/1028415X.2018.1533269

Ighodaro OM. Molecular pathways associated with oxidative stress in diabetes mellitus. Biomed Pharmacother. 2018 Dec;108:656-62. PMID: 30245465. doi: https://doi.org/10.1016/j.biopha.2018.09.058

Kuo J. Electron microscopy: Methods and pro­tocols. New York: Humana Press; 2014. p. 799. doi: https://doi.org/10.1007/978-1-62703-776-1

Apostolova N, Iannantuoni F, Gruevska A, Mun­tane J, Rocha M, Victor VM. Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions. Redox Biol. 2020 Jul;34:101517. Epub 2020 May 25. PMID: 32535544, doi: https://doi.org/10.1016/j.redox.2020.101517

Ghosh S, Lakshmanan AP, Hwang MJ, Kubba H, Mushannen A, Triggle CR, Ding H. Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic con­ditions. Biochem Pharmacol. 2015 Dec 1;98(3):412-21. PMID: 26467186. doi: https://doi.org/10.1016/j.bcp.2015.10.008

Rena G, Hardie DG, Pearson ER. The mecha­nisms of action of metformin. Diabetologia. 2017 Sep;60(9):1577-85. Epub 2017 Aug 3. PMID: 28776086; doi: https//doi.org/10.1007/s00125-017-4342-z

Vizir VA, Makurina GI. State of free-radical processes and antioxidant defence of patients with psoriasis and concomitant essential hypertension. Zaporozhye Medical Journal. 2016 Oct;4(97):21-28. doi: https://doi.org/10.14739/2310-1210.2016.4.79730

Published

2020-10-05

How to Cite

1.
Lievykh АE, Bondarenko NS, Dronov SN, Mamchur VI, Tverdokhlib IV, Zhyliuk VI. Experimental substantiation of the expediency of the combined use of piracetam and metformin for pharmacological correction of cognitive disorders in conditions of prolonged hyperglycemia. Med. perspekt. [Internet]. 2020Oct.5 [cited 2024Nov.22];25(3):30-9. Available from: https://journals.uran.ua/index.php/2307-0404/article/view/214647

Issue

Section

THEORETICAL MEDICINE