INFLUENCE OF CHRONIC ALCOHOLIZATION OF RATS ON THE PARAMETERS OF THE THIOL-DISULPHIDE SYSTEM OF THE BRAIN AND SEARCH FOR NEW PHARMACOTHERAPEUTIC CORRECTION SCHEMES FOR IMBALANCE
About the author:
Sokolik O. P., Prozorova G. O.
Heading:
CLINICAL AND EXPERIMENTAL MEDICINE
Type of article:
Scentific article
Annotation:
Mechanisms of damage of neuronal cells in different diseases of the brain are important problem of neurology and pharmacology for understanding the ways of pharmacological correction of violations, which are being intensively studied now throughout the world. Purpose of the study: to study the molecular and biochemical mechanisms of neuronal death against the background of the development of imbalance of the thiol-disulfide system in conditions of chronic alcohol intoxication and to develop new methods of pharmacological correction. Object and research methods: the experiment was performed on 50 white male Wistar rats, 250-300 gr. Chronic alcohol intoxication was achieved by daily introgastric introduction during the first 10 days – 15% solution of ethanol in doses of 4 g/kg, next 10 days – 15% solution of ethanol in doses of 6 g/kg and in another 10 days rats get 25% ethanol solution in doses of 3 g/kg. On the 30-th day we stopped alcoholization and conducted experimental drug therapy (cerebrocurin, cortexin and cerebrolysin) and continued surveillance within 14 days. Results. Under conditions of chronic alcohol intoxication and toxic brain damage, nitrosative stress develops in the early stages, leading to nitrosation of thiols, changing the thiol-disulfide balance of mitochondrial pore proteins. Oxidative and carbonyl stress develops, which significantly displace the thiol-disulfide balance in the direction of oxidized thiols, develops stable mitochondrial dysfunction with a deficiency of cell energy reserves, the development of autocoidosis, a change in the genome response, and the cell dies on the way of necrosis. Conclusions. Neuropeptide preparations – cerebrocurin, cortexin and cerebrolysin have a pronounced neuroprotective effect in relation to normalizing the balance of the thiol-disulfide system and reducing the activity of oxidative and nitrosative stress and mitochondrial dysfunction.
Tags:
glutathione system, oxidative stress, nitrosative stress, chronic alcohol intoxication, neuroprotection
Bibliography:
- Belenichev I, Burlaka B, Puzyrenko A, Ryzhenko O, Kurochkin M, Yusuf J. Management of amnestic and behavioral disorders after ketamine anesthesia. Georgian Med News. 2019 Sep;294:141-5.
- Sayd A, Vargas-Caraveo A, Perea-Romero I. Depletion of brain perivascular macrophages regulates acute restraint stress-induced neuroinflammation and oxidative/nitrosative stress in rat frontal cortex. Eur Neuropsychopharmacol. 2020;34:50-64. DOI: 10.1016/j. euroneuro.2020.03.004
- Mazur I, Belenichev I, Kucherenko L, Bukhtiyarova N, Puzyrenko A, Khromylova O, et al. Antihypertensive and cardioprotective effects of new compound 1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide (Hypertril). Eur J Pharmacol. 2019 Jun 15;853:336-44. DOI: 10.1016/j. ejphar.2019.04.013
- Belenichev I, Gorchakova N, Puzyrenko A, Kovalenko S, Bukhtiayrova N. Synthesis of the new 2-(3,4-dihydro-3-oxo-2h-[1,2,4]triazino[4,3-c] quinazolin-4-yl) acetic acid derivatives and analysis of their antioxidant activity in nitrosative stress models. Georgian Med News. 2018 Jul-Aug;280-281:173-8.
- Gritsyna YV, Salmov NN, Bobylev AG, Fadeeva IS, Fesenko NI, Sadikova DG, et al. Chronic Alcohol Intoxication Is Not Accompanied by an Increase in Calpain Proteolytic Activity in Cardiac Muscle of Rats. Biochemistry. 2017 Feb;82(2):168-75. DOI: 10.1134/S0006297917020080
- Stefanov OV, redaktor. Doklinichni doslidzhennya likarsʹkykh zasobiv: metodychni rekomendatsiyi. K.: «Avitsena»; 2001. 528 s. [in Ukrainian].
- Gushcha VK, Lelevich SV, Sheibak VM. Neĭromediatornye narusheniia v nekotorykh otdelakh golovnogo mozga krys i ikh korrektsiia pri khronicheskoĭ i preryvistoĭ alkogol’noĭ. Biomed Khim. 2019 Jan;65(1):21-7. DOI: 10.18097/PBMC20196501021 [in Russian].
- Shayakhmetova GM, Bondarenko LB, Kovalenko VM. Multiparameter rodent chronic model for complex evaluation of alcoholism-mediated metabolic violations. J Basic Clin Physiol Pharmacol. 2015 Jan;26(1):43-51. DOI: 10.1515/jbcpp-2013-0163
- Nkpaa KW, Amadi BA, Wegwu MO, Farombi EO. Ethanol increases manganese-Induced spatial learning and memory deficits via oxidative/ nitrosative stress induced p53 dependent/independent hippocampal apoptosis. Toxicology. 2019 Apr 15;418:51-61. DOI: 10.1016/j. tox.2019.03.001
- Abdallah MA, Singal AK. Mitochondrial dysfunction and alcohol-associated liver disease: a novel pathway and therapeutic target. Signal Transduct Target Ther. 2020 Mar 3;5:26. DOI: 10.1038/s41392-020-0128-8
- Buján GE, Serra HA, Molina SJ, Guelman LR. Oxidative Stress-Induced Brain Damage Triggered by Voluntary Ethanol Consumption during Adolescence: A Potential Target for Neuroprotection? Curr Pharm Des. 2019;25(45):4782-90. DOI: 10.2174/13816128256661912 09121735
- Abdelmegeed M, Mukhopadhyay P. Understanding the roles and mechanisms of oxidative stress in diseases, tissue injury, and cell death in vivo and in vitro: Therapeutic possibilities of antioxidants. Food Chem Toxicol. 2019 May;127:70-1. DOI: 10.1016/j.fct.2019.02.040
- Shamakina IY, Proskuryakova TV, Shokhonova VA, Ulyanova EV, Anokhin PK, Tapabarko IE, Anokhina IP. Vliyanie kabergolina na potreblenie alkogolya i ekspressiyu gena DRD2 v mozge krys s khronicheskoi alkogol’noi intoksikatsiei. Zh nevrol psikhiatr im SS Korsakova. 2016;116(11.2):74-80. DOI: 10.17116/jnevro201611611274-80 [in Russian].
- Fontes-Júnior EA, Maia CS, Fernandes LM, Gomes-Leal W, Costa-Malaquias A, Lima RR, et al. Chronic Alcohol Intoxication and Cortical Ischemia: Study of Their Comorbidity and the Protective Effects of Minocycline. Oxid Med Cell Longev. 2016;2016:1341453. DOI: 10.1155/2016/1341453
- Hsieh YJ, Wu LC, Ke CC, Chang CW, Kuo JW, Huang WS, et al. Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain. Alcohol Clin Exp Res. 2018 Feb;42(2):329-37. DOI: 10.1111/acer.13573
- Liew HK, Cheng HY, Huang LC, Li KW, Peng HF, Yang HI, et al. Acute Alcohol Intoxication Aggravates Brain Injury Caused by Intracerebral Hemorrhage in Rats. J Stroke Cerebrovasc Dis. 2016 Jan;25(1):15-25. DOI: 10.1016/j.jstrokecerebrovasdis.2015.08.027
- Pavlov AL, Savin AA, Bogomolov DV, Pavlova AZ, Larev ZV. Klinicheskaia patomorfologiia i tanatogenez razlichnykh form alkogol’noĭ intoksikatsii. Sud Med Ekspert. 2018;61(3):11-4. DOI: 10.17116/sudmed2018613-14 [in Russian].
- Erickson EK, Grantham EK, Warden AS, Harris RA. Neuroimmune signaling in alcohol use disorder. Pharmacol Biochem Behav. 2019 Feb;177:34-60. DOI: 10.1016/j.pbb.2018.12.007
- Cook JE, Chandler C, Rüedi-Bettschen D, Taylor I, Patterson S, Platt DM. Changes in the elimination and resurgence of alcohol-maintained behavior in rats and the effects of naltrexone. Psychol Addict Behav. 2020 Feb;34(1):10-22. DOI: 10.1037/adb0000525
Publication of the article:
«Bulletin of problems biology and medicine» Issue 4 (158), 2020 year, 193-199 pages, index UDK 615.214.31:616.89–008