The study of the potential hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole and IEM-2320



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Abstract

BACKGROUND:  Toxic hepatitis is characterized by a significant severity of the course and by high mortality. So, search for effective means of correcting this condition seems to be relevant. It has previously been shown that some thiazolo[5,4-b]indole derivatives are capable to prevent experimental toxic liver damage in laboratory animals. In continuation of this direction, the study of the hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole (2-ABT) and IEM-2320 was undertaken.

AIM:  To study the potential hepatoprotective properties of 2–ABT and IEM-2320 in acute carbon tetrachloride poisoning.

MATERIALS AND METHODS: Experiments were carried out on 30 male white mongrel rats (150-270 g.) On a model of carbon tetrachloride poisoning (50% solution of CCl4 in vaseline oil, 0.2 ml/100 g of body weight), the potential hepatoprotective properties of 2-ABT (32 mg/kg) and IEM-2320 (20 mg/kg) were investigated. Ademethionine (Heptral, AbbVie, S.r.L, Italy) at a dose of 20 mg/kg was used as a comparison drug. The studied drugs were administered intraperitoneally 4 times: one hour before the introduction of CCl4, and then - for three subsequent days after the poisoning with CCl4. The results were compared with those of 2 control groups. Animals of the 1st control group were not exposed to CCl4, instead of the studied drugs, they were injected with an equivalent volume of saline solution (0.2 ml / 100 g of body weight). Animals of the 2nd control group did not receive any treatment after the CCl4 poisoning. Blood was taken on the seventh day of the experiment. The total contents of protein, glucose, and total cholesterol in blood serum were determined, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were evaluated.

RESULTS: Under the CCl4 poisoning, the administration of 2-ABT led to a significant decrease in the concentrations of glucose, total protein, total cholesterol and ALT activity. When IEM-2320 was administered under the condition of poisoning, a decrease in the concentrations of total protein, glucose, urea, total cholesterol, and the ALT activity was observed.

CONCLUSIONS: A significant decrease in the biochemical parameters of blood serum after administration of 2-ABT and IEM-2320 under the condition of CCl4 poisoning demonstrates thir potential hepatoprotective properties under acute hepatotropic poisonings.

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About the authors

Dmitrii Ivanovich Klimenko

FSBEI of HE "North-Western State Medical University named after I.I. Mechnikov"

Email: dima.klimenko999@mail.ru
ORCID iD: 0009-0007-8168-7228

5th year student

Russian Federation, 195067, St. Petersburg, Piskarevsky Ave., 47

Demidova Olegovna Demidova

FSBI ”S.N. Golikov` Research Clinical Center of Toxicology of the Federal Medical Biological Agency of Russia”

Email: bedskaya.667@yandex.com
ORCID iD: 0009-0003-0820-8471
SPIN-code: 1618-1510

2-year resident, junior researcher at the Laboratory of Morphology and Electron Microscopy

Russian Federation, 192019, St. Petersburg, Bekhtereva str., 1

Tatevik Tigranovna Asatryan

FSBEI of HE "North-Western State Medical University named after I.I. Mechnikov"

Email: tatevik.asatryan@szgmu.ru
ORCID iD: 0000-0002-9146-3080
SPIN-code: 5587-1360

Ph.D. of Medical Sciences, Associate Professor of the Department of Clinical Laboratory Diagnostics, Biological and General Chemistry named after V.V. Sokolovsky, Head of the Central Research Laboratory

Russian Federation, 195067, St. Petersburg, Piskarevsky Ave., 47

Leonid Vitalievich Myznikov

FSBSI "Institute of Experimental Medicine", S.V. Anichkov` Department of Neuropharmacology

Email: postleo@mail.ru
ORCID iD: 0000-0002-0863-3027
Scopus Author ID: 39113

Dr.  Sci.  (Chem.), Research Associate, Department of Neuropharmacology

Russian Federation, 197022, St. Petersburg, Akademika Pavlova str., 12

Natalia Dvitrievna Nadbitova

FSBSI "Institute of Experimental Medicine", S.V. Anichkov` Department of Neuropharmacology

Email: natali_805@mail.ru
ORCID iD: 0000-0002-2957-226X
SPIN-code: 4153-1270
Scopus Author ID: 57732629300
ResearcherId: JBS-0803-2023

Ph.D. of Medical Sciences, Researcher at the S.V.Anichkov Department of Neuropharmacology

Russian Federation, 197022, St. Petersburg, Akademika Pavlova str., 12

Ekaterina Valeryevna Matveeva

FSBEI of HE "North-Western State Medical University named after I.I. Mechnikov"

Email: lika.hell@mail.ru
ORCID iD: 0009-0006-0695-6400

5th year student

Russian Federation, 195067, St. Petersburg, Piskarevsky Ave., 47

Sofia Vyacheslavovna Moskvicheva

FSBEI of HE "North-Western State Medical University named after I.I. Mechnikov"

Email: moskvichevasofia@yandex.ru
ORCID iD: 0009-0007-6058-2945

3rd year student

Russian Federation, 195067, St. Petersburg, Piskarevsky Ave., 47

Sofya Andreevna Borzykh

FSBEI of HE "North-Western State Medical University named after I.I. Mechnikov"

Author for correspondence.
Email: borzih.s2002@gmail.com
ORCID iD: 0009-0002-6882-8421

4th year student, Laboratory assistant researcher at the Central Research Laboratory

Russian Federation, 195067, St. Petersburg, Piskarevsky Ave., 47

Natalia Removna Evdokimova

FSBSI "Institute of Experimental Medicine", S.V. Anichkov` Department of Neuropharmacology

Email: enatalyar@mail.ru
ORCID iD: 0000-0003-4318-2556

PhD, Researcher of the Department of Neuropharmacology named after S.V. Anichkov

Russian Federation, 197022, St. Petersburg, Akademika Pavlova str., 12

Margarita Vitalievna Lukk

Military medical academy of S.M. Kirov, Saint-Petersburg

Email: m_lukk@mail.ru
ORCID iD: 0009-0003-0853-7769
SPIN-code: 5125-6277

Ph.D., Associate Professor, Associate Professor of the Department of Pharmacology

Russian Federation, 194044, St. Petersburg, Akademika Lebedeva str., 6

Stanislav Mikhailovich Ramsh

St. Petersburg State Institute of Technology (Technical University), St. Petersburg

Email: sramsh@technolog.edu.ru
ORCID iD: 0000-0003-4613-068X
SPIN-code: 6777-2246

Dr. Sci. (Chem.), Professor, Head of the Department of Chemical Technology of Organic Dyes and Phototropic Compounds

Russian Federation, 190013, St. Petersburg, Moskovski ave., 26,

Vyacheslav Pavlovich Ganapolsky

Military medical academy of S.M. Kirov, Saint-Petersburg

Email: ganvp@mail.ru
ORCID iD: 0000-0001-7685-5126
SPIN-code: 9872-8841

Colonel of the Medical Service, M.D., D.Sc. (Medicine), Acting Head of the Pharmacology Department

Russian Federation, 194044, St. Petersburg, Akademika Lebedeva str., 6

Inessa Vladimirovna Karpova

FSBSI "Institute of Experimental Medicine", S.V. Anichkov` Department of Neuropharmacology

Email: inessa.karpova@gmail.com
ORCID iD: 0000-0001-8725-8095
SPIN-code: 9874-4082

MD, Associate Professor, Senior Researcher of the Department of Neuropharmacology named after S.V. Anichkov

Russian Federation, 197022, St. Petersburg, Akademika Pavlova str., 12

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