Correction of psychoneurological signs of acute alcohol intoxication in rats with a new acetylcysteine-based composition

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Abstract

The aim of the study is an experimental confirmation of the use of a new combination of biologically active substances with tonic and antioxidant effects. This combination contains acetylcysteine in its composition to reduce the severity of psychoneurological consequences of alcohol intoxication.

Materials and methods. The study was conducted on male Wistar rats. The post-intoxication state was simulated by a single injection of ethanol (3 g/kg, intraperitoneally). Half an hour after awakening, the rats were divided into groups, which were injected with saline, acetylcysteine (1 g/kg), taurine (20 mg/kg), caffeine (20 mg/kg), succinic acid (100 mg/kg), lipoic acid (100 mg/kg), pyridoxine (400 mg/kg), or a combination of acetylcysteine with all these substances taken in a twice lower dose (except taurine). Before the treatment and 3 hours after it, the degree of neurological disorders was fixed according to the Combs and D’Alecy scale, in the Open Field test and the Adhesion test. Then the animals were euthanized to assess the level of glutathione, triglycerides and malondialdehyde (MDA) in liver homogenates, to determine the activity of enzymatic antioxidant systems and serum aminotransferases.

Results. In the animals injected with alcohol, there were evident signs of neuropsychiatric disorders, manifested in a low motor activity and a decrease in fine motor skills. This state did not change after an oral administration of saline. After the administration of acetylcysteine, taurine, caffeine, succinic and lipoic acids, pyridoxine and, to a greater extent, their compositions, the compensation of neuropsychiatric disorders and improvement of fine motor skills were notified. In the liver of these animals, the levels of glutathione, MDA, triglycerides, and the activity of antioxidant defense enzymes corresponded to the physiological norm.

Conclusion. The introduction of a combination of acetylcysteine with taurine, caffeine, pyridoxine, lipoic and succinic acids after an acute alcohol intoxication, to a greater extent than each of the substances separately, contributes to the function retention of the antioxidant system of hepatocytes. Besides, it reduces the level of their dystrophic changes and leads to a decrease in the severity of psychoneurological disturbances in the experimental animals.

About the authors

Denis V. Kurkin

Volgograd State Medical University

Email: strannik986@mail.ru
ORCID iD: 0000-0002-1116-3425

Doctor of Sciences (Pharmacy), senior researcher of the laboratory of cardiovascular medications, Scientific Center of Drug Research, the Head of interdepartmental center of practical and scientific work of Faculty of Pharmacy

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Evgeny I. Morkovin

Volgograd State Medical University; Volgograd Medical Research Center

Author for correspondence.
Email: e.i.morkovin@gmail.com
ORCID iD: 0000-0002-7119-3546

Candidate of Sciences (Medicine), Associate Professor, the head of the laboratory of neuropsychotropic drugs, Scientific Center of Drug Research; senior researcher of the laboratory of genomic and proteomic researches

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131; 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Nazar A. Osadchenko

Volgograd State Medical University

Email: n.a.osadchenko@gmail.com
ORCID iD: 0000-0002-7398-2186

post-graduate student, Department of Pharmacology and Pharmacy

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Dmitry A. Bakulin

Volgograd State Medical University

Email: mbfdoc@gmail.com
ORCID iD: 0000-0003-4694-3066

Candidate of Sciences (Medicine), senior researcher of the laboratory of cardiovascular medications, Scientific Center of Drug Research

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Elizaveta E. Abrosimova

Volgograd State Medical University

Email: abrosimiva.volgmed@gmail.com
ORCID iD: 0000-0002-6472-6906

post-graduate student, Department of Pharmacology and Pharmacy

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Marina A. Dubrovina

Volgograd State Medical University

Email: dubrovina.volgmed@gmail.ru
ORCID iD: 0000-0003-1903-8589

post-graduate student, Department of Pharmacology and Pharmacy

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Nikolay S. Kovalev

Volgograd State Medical University

Email: kovalev.volgmed@gmail.com
ORCID iD: 0000-0003-3498-3810

post-graduate student, Department of Pharmacology and Pharmacy

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Yulia V. Gorbunova

Volgograd State Medical University

Email: yvgorbunova@yandex.ru

Candidate of Sciences (Pharmacy), document controller of the Department of Pharmacology and Pharmacy

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

Ivan N. Tyurenkov

Volgograd State Medical University

Email: fibfuv@mail.ru
ORCID iD: 0000-0001-7574-3923

Doctor of Sciences (Medicine), professor, Corresponding Member of the Russian Academy of Sciences, the Head of the Department of Pharmacology and Biopharmaceutics, Faculty of Advanced Medical Studies, Head of laboratory of cardiovascular medications, Scientific Center of Drug Research

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

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2. Figure 1 – Study design

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3. Figure 2 – The levels of neurological deficits assessed by the Combs & D’Alecy scale (A) and the time of removing a foreign object from the volar surface of the rats’ fore paws (B), indicators of locomotor (C) and exploratory (D) activities in the open field test in the rats after acute alcohol intoxication

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4. Figure 3 – Activity of superoxide dismutase (SOD), aspartate aminotransferase (AST) and alanine aminotransferase (ALT); the content of triglycerides, malonic dialdehyde (MDA), glutathione in rat liver homogenates, obtained after acute alcohol intoxication

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Copyright (c) 2020 Kurkin D.V., Morkovin E.I., Osadchenko N.A., Bakulin D.A., Abrosimova E.E., Dubrovina M.A., Kovalev N.S., Gorbunova Y.V., Tyurenkov I.N.

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