EXPERIMENTAL RESEARCH
Pharmacology
doi: 10.25005/2074-0581-2026-28-3-728-738
HEPATOPROTECTIVE PROPERTIES OF CYANOTHIOACETAMIDE DERIVATIVES WITH ANALGESIC ACTIVITY IN ACUTE PARACETAMOL-INDUCED HEPATITIS

E.YU. BIBIK1, D.R. BUKHTOYAROVA1, K.A. FROLOV1,2, S.G. KRIVOKOLYSKO1,2

1St. Luke Lugansk State Medical University, Lugansk, Russian Federation
2Vladimir Dahl Lugansk State University, Lugansk, Russian Federation

Objective: To investigate the effects of novel cyanothioacetamide derivatives with analgesic activity on blood biochemical parameters in rats with acute paracetamol-induced hepatitis (APH).

Methods: The experiments were performed on 80 adult male outbred albino rats weighing 250-300 g. The animals were divided into eight groups of 10 rats each: an intact group, a control group, a reference group receiving thiotriazolin at a dose of 10 mg/kg, and five experimental groups receiving original α-cyanothioacetamide derivatives coded Mar-014, Mar-037, Mar-075, d02-123, and TD-0331 at a dose of 5 mg/kg in a preventive/therapeutic regimen. APH was experimentally induced by administering paracetamol at 1,500 mg/kg during the first two days, one hour after administration of the test compounds. On day 5, the animals were euthanized, and blood biochemical parameters were determined.

Results: Compared with corresponding values in intact rats, total bilirubin in the control group was 2.8-fold higher, and direct bilirubin was 2.5 - fold higher. Alanine aminotransferase (ALT) activity increased by 59.3%, aspartate aminotransferase (AST) activity by 63.6%, and alkaline phosphatase (ALP) activity by 91.5%. In the reference group and all experimental groups, total and direct bilirubin levels remained comparable to those of intact animals. Experiments in albino rats with experimentally induced APH demonstrated pronounced hepatoprotective properties of the de novo synthesized heterocyclic compounds that had previously been shown to possess analgesic and anti-inflammatory activity. Biochemical blood parameters in rats with APH indicate that the novel heterocyclic compounds coded d02-123, Mar-014, Mar-075, and TD-0331 prevented acute paracetamol-induced liver injury without significant alterations in biochemical markers of liver function, indirectly indicating preservation of hepatocyte integrity. Given our previous studies showing that these compounds have analgesic and anti-inflammatory activity exceeding that of metamizole, ibuprofen, indomethacin, and meloxicam by several-fold to tens-fold, the hepatoprotective properties identified in the present study support further preclinical investigation.

Conclusion: Among the novel heterocyclic compounds belonging to the cyano-thioacetamide derivative series, compounds coded d02-123, Mar-014, Mar-075, and TD-0331 demonstrated hepatoprotective activity

Keywords: Liver, hepatotoxicity, hepatoprotective agents, cyanothioacetamide, paracetamol-induced hepatitis.

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Authors' information:

Bibik Elena Yurievna,
Doctor of Medical Sciences, Full Professor, Head of the Department of Fundamental and Clinical Pharmacology of the St. Luke Lugansk State Medical University
ORCID ID: 0000-0001-7470-608X
SPIN: 9832-4659
Author ID: 1204736
Е-mail: helen_bibik@mail.ru

Bukhtoyarova Darya Romanovna,
Junior Researcher at the Research Laboratory, Senior Laboratory Assistant at the Department of Fundamental and Clinical Pharmacology, St. Luke Lugansk State Medical University
ORCID ID: 0009-0001-6658-3574
SPIN: 9467-9355
Author ID: 1280200
Е-mail: darya.rupengey.00@mail.ru

Frolov Konstantin Aleksandrovich,
Сandidate of Chemical Sciences, Associate Professor, Leading Researcher of the Research Laboratory of the St. Luke Lugansk State Medical University; Associate Professor of the Department of Chemistry and Innovative Technologies, Vladimir Dahl Lugansk State University
ORCID ID: 0000-0002-8045-7582
SPIN: 5418-1054
Author ID: 1250685
Е-mail: kа.frolov@inbox.ru

Krivokolysko Sergey Gennadievich,
Doctor of Chemical Sciences, Full Professor, Principal Researcher at the Scientific Research Laboratory of the St. Luke Lugansk State Medical University; Head of the Department of Chemistry and Innovative Technologies, Head of the «ChemEx» Research Laboratory, Vladimir Dahl Lugansk State University
ORCID ID: 0000-0001-9879-9217
SPIN: 7682-4986
Author ID: 133297
Е-mail: ksg-group-lugansk@mail.ru

Information about support in the form of grants, equipment, medications

This study was financially supported within the framework of the State Assignment of the Ministry of Science and Higher Education of the Russian Federation, project entitled “Novel heterocyclic derivatives of methylene-active nitriles, thioamides, and selenamides: Synthesis, properties, and biological activity” (project code FREE-2023-0002), as well as by the State Assignment of the Ministry of Health of the Russian Federation, project entitled “Search for novel highly effective and safe medicinal agents among previously unknown domestically produced heterocyclic cyanothioacetamide derivatives” (project code ZUNP-2024-0002). The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Bukhtoyarova Darya Romanovna
Junior Researcher at the Research Laboratory, Senior Laboratory Assistant at the Department of Fundamental and Clinical Pharmacology, St. Luke Lugansk State Medical University

291045, Russian Federation, Lugansk, 1G Quarter of 50th Anniversary of the Defence of Lugansk

Tel.: +7 (959) 1115848

Е-mail: darya.rupengey.00@mail.ru


This work is licensed under a Creative Commons Attribution 4.0 International License.

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