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

Abstract

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.

Keywords

• glutathione system
• oxidative stress
• nitrosative stress
• chronic alcohol intoxication
• neuroprotection