Experimental substantiation of the expediency of the combined use of piracetam and metformin for pharmacological correction of cognitive disorders in conditions of prolonged hyperglycemia
Keywords:alloxan-induced hyperglycemia, diabetic encephalopathy, cognitive deficit, metformin, piracetam
AbstractChronic 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.
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
How to Cite
Copyright (c) 2020 Medicni perspektivi (Medical perspectives)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Submitting manuscript to the journal "Medicni perspektivi" the author(s) agree with transferring copyright from the author(s) to publisher (including photos, figures, tables, etc.) editor, reproducing materials of the manuscript in the journal, Internet, translation into other languages, export and import of the issue with the author’s article, spreading without limitation of their period of validity both on the territory of Ukraine and other countries. This and other mutual duties of the author and all co-authors separately and editorial board are secured by written agreement by special form to use the article, the sample of which is presented on the site.
Author signs a written agreement and sends it to Editorial Board simultaneously with submission of the manuscript.