Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.10.443

Abstract

Introduction: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic benefit, they can also have serious side effects. The most serious of these is the ulcerogenic effect, which can result in a decline in the quality of life or even death. This calls for the search for and creation of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system. The aim of the study was to investigate the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activities of N-isopropenylimidazole zinc complex derivative.

Materials and Methods: Experiments in rats and mice were used to determine the median lethal dose LD50 for N-isopropenylimidazole zinc complex derivative (laboratory name Pilim-1). Experimental models of acute exudative inflammation and chronic proliferative inflammation were used. In the first case, the inflammation was induced by sub-plantar injection of carrageenan and a complete Freund’s adjuvant into the hind paw of rats. In the second case, the inflammation was induced by the implantation of a sterile cotton pellet (“cotton pellet–induced granuloma”) under the skin of rats. Acute and tonic pain, visceral, and somatic deep pain were simulated using the formalin test in rats and the acetic acid-induced writhing test in mice, respectively. The ulcerogenic and anti-ulcerogenic effects of Pilim-1 were studied in rat experiments. Pilim-1 and the reference drugs diclofenac, indomethacin and famotidine were administered intragastrically.

Results and Discussion: Pilim-1 showed marked anti-inflammatory and analgesic effects, demonstrated less toxicity than diclofenac and indomethacin, while its activity is comparable to diclofenac and superior to indomethacin. Its therapeutic index is higher than that of indomethacin and diclofenac and, in contrast, it essentially has no ulcerogenic effect and exhibits stronger anti-ulcerogenic activity than famotidine. It appears that the anti-inflammatory, analgesic, and gastroprotective properties of Pilim-1 are largely due to its antioxidant and antihypoxic properties, its inhibitory effects on cyclooxygenase and 5-lipoxygenase, and the presence of imidazole and zinc in its structure, both of which have a wide range of biological activity.

Conclusion: Pilim-1 can be recommended for further preclinical studies due to its relatively low (practically absent) ulcerative activity, strong anti-inflammatory, analgesic, and anti-ulcerative effects, greater therapeutic index, and less acute toxicity in comparison with diclofenac and indomethacin.

Graphical Abstract

Keywords:

analgesic activity, anti-ulcerogenic activity, diclofenac, indomethacin, N-isopropenylimidazole zinc complex derivative, acute toxicity, anti-inflammatory activity, ulcerogenic effect

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Author Contribution

Pavel A. Galenko-Yaroshevsky, Kuban State Medical University

Сorresponding member of the Russian Academy of Sciences, Holder of Advanced Doctorate (Doctor Habil. of Science) in Medical Sciences, Professor, Head of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; е-mail: Galenko.Yaroсhevsky@gmail.com; ORCID ID https://orcid.org/0000-0003-3190-1437. The author’s contribution: concept development–conceptualization and direction development of the research; methodology development and design; generation of key aims and objectives.

Olga V. Shelemekh, Rostov State Medical University

Postgraduate student of the Department of Dentistry No.4 of Rostov State Medical University, Rostov-on-Don, Russia; e-mail: lioli777@yandex.ru; ORCID ID https://orcid.org/0000-0003-3488-9971. The author’s contribution: experimentation,data collection and analysis, statistical data processing and compilation of the manuscript.

Viktor L. Popkov, Kuban State Medical University

Holder of Advanced Doctorate (Doctor Habil. of Science) in Medical Sciences, Professor of the Department of Orthopedic Dentistry of Kuban State Medical University, Krasnodar, Russia; e-mail: vict.popkoff2015@yandex.ru; ORCID ID https://orcid.org/0000-0001-7362-0073. The author’s contribution: defining the key aims and objectives, critical revision of the manuscript and its analysis, providing valuable comments.

Andrey V. Zadorozhniy, Rostov State Medical University

PhD in Medical Sciences, Associate Professor, Head of the Department of Dentistry No.4 of Rostov State Medical University, Rostov-on-Don, Russia;e-mail: stomvr1@gmail.com; ORCID IDhttps://orcid.org/0000-0001-9552-8542. Author's contribution: editing and preparation of the article text, participation in scientific design; resource support of the research–C&E materials, animals, instruments, computers for analysis; correction of the final version of the article

Irina B. Nektarevskaya, Rostov State Medical University

PhD in Medical Sciences, Associate Professor of the Department of Dentistry No.4 of Rostov State Medical University, Rostov-on-Don, Russia; е-mail: nektir4546@mail.ru; ORCID ID https://orcid.org/0009-0009-6733-9977. Author's contribution: search for and analysis of information; animal keeping control, participation in the analysis of the research results.

Natalia D. Bunyatyan, I.M. Sechenov First Moscow State Medical University; Federal State Budgetary Institution "Scientific Centre for Expert Evaluation of Medicinal Products" of the Ministry of Health of the Russian Federation

Holder of Advanced Doctorate (Doctor Habil. of Science) in Pharmaceutical Sciences, Professor, Head of the Department of Pharmaceutical Technology and Pharmacology of Institute of Professional Education of I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Russia; Federal State Budgetary Institution "Scientific Centre for Expert Evaluation of Medicinal Products" of the Ministry of Health of the Russian Federation, Moscow, Russia; e-mail: ndbun@mail.ru; ORCID ID https://orcid.org/0000-0001-9466-1261. The author’s contribution: participation in preparing the final version of the manuscript in terms of visualization and data presentation.

Roman A. Murashko, Specialistsof Kuban State Medical University

Holder of Advanced Doctorate (Doctor Habil. of Science) in Medical Sciences, Associate Professor of the Department of Oncology withthe Course of Thoracic Surgery, Faculty of Advanced Trainingand Professional Retraining of Specialistsof Kuban State Medical University, Krasnodar, Russia; е-mail: ramurashko@rambler.ru; ORCID ID https://orcid.org/0000-0001-8873-8461. Author's contribution: defining the key aims and objectives, critical revision of the manuscript and providing valuable comments.

Svetlana A. Lebedeva, I.M. Sechenov First Moscow State Medical University

Holder of Advanced Doctorate (Doctor Habil. of Science) in Biological Sciences, Professor of the Department of Pharmacology of Institute of Pharmacy named after A.P. Nelyubin of I.M. Sechenov First Moscow State Medical University, Moscow, Russia; e-mail: Lebedeva502@yandex.ru; ORCID ID https://orcid.org/0000-0001-8769-1040. The author’s contribution: defining the key aims and objectives; critical revision of the manuscript, providing valuable comments.

Anait V. Zelenskaya, Kuban State Medical University

PhD in Medical Sciences, Associate Professor of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; е-mail: anait_06@mail.ru; ORCID ID https://orcid.org/0000-0001-9512-2526. Author's contribution: analysis and interpretation of research results; preparation and editing of the article text; participation in scientific design.

Aleksandr V. Uvarov, Kuban State Medical University

PhD in Medical Sciences, Associate Professor of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; e-mail: ytovkach@rambler.ru; ORCID ID https://orcid.org/0000-0003-0337-2689. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Olga N. Gulevskaya, Kuban State University of Physical Culture, Sports and Tourism

PhD in Medical Sciences, Associate Professor of the Department of Adaptive Physical Culture of Kuban State University of Physical Culture, Sports and Tourism, Krasnodar, Russia; e-mail: olga.stoyalova@bk.ru, ORCID ID https://orcid.org/0000-0001-7205-2473. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Lusine O. Alukhanyan, Kuban State Medical University

PhD in Medical Sciences, Associate Professor of the Department of Pediatric Dentistry, Orthodontics and Maxillofacial Surgery of Kuban State Medical University, Krasnodar, Russia; е-mail: lus.0912@mail.ru; ORCID ID https://orcid.org/0009-0005-1752-2491. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Tereza R. Glechyan, Kuban State Medical University,

 Assistant Professor of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; e-mail: t_g91@mail.ru; ORCID ID https://orcid.org/0009-0002-4983-2433. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Alina V. Sergeeva, Kuban State Medical University

Assistant Professor of the Department of Pharmacology of Kuban State Medical University, Krasnodar, Russia; е-mail: alina_sergeeva_v@mail.ru; ORCID ID https://orcid.org/0000-0003-4335-2156. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Alina V. Kornetskaya, Kuban State Medical University

3rdyear student of the Faculty of Medicine of Kuban State Medical University, Krasnodar, Russia; е-mal: alinaleigh@mail.ru; ORCID ID https://orcid.org/0009-0007-7452-2871. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

Nikolay E. Korovaykin, Kuban State Medical University

3rdyear student of the Faculty of Medicine of Kuban State Medical University, Krasnodar, Russia; е-mail: nikkoro@bk.ru; ORCID ID https://orcid.org/0009-0004-9543-7906. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

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Published

13-02-2024

How to Cite

Galenko-Yaroshevsky PA, Shelemekh OV, Popkov VL, Zadorozhniy AV, Nektarevskaya IB, Bunyatyan ND, Murashko RA, Lebedeva SA, Zelenskaya AV, Uvarov AV, Gulevskaya ON, Alukhanyan LO, Glechyan TR, Sergeeva AV, Kornetskaya AV, Korovaykin NE (2024) Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative. Research Results in Pharmacology 10(1): 23–43. https://doi.org/10.18413/rrpharmacology.10.443

Issue

Vol. 10 No. 1 (2024)

Section

Experimental Pharmacology

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Copyright (c) 2024 Pavel A. Galenko-Yaroshevsky, Olga V. Shelemekh, Viktor L. Popkov, Andrey V. Zadorozhniy, Irina B. Nektarevskaya, Natalia D. Bunyatyan, Roman A. Murashko, Svetlana А. Lebedeva, Anait V. Zelenskaya, Aleksandr V. Uvarov, Olga N. Gulevskaya, Lusine O. Alukhanyan, Tereza R. Glechyan, Alina V. Sergeeva, Alina V. Kornetskaya, Nikolay E. Korovaykin

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