Study of anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.10.515

Abstract

Introduction: The combination treatment of patients with dentition problems including endodontic-periodontal lesions (EPL) is known to widely involve anti-inflammatory drugs, including non-steroidal anti-inflammatory agents, and antimicrobial drugs, in particular antibiotics and antiseptics, from which the former often lead to the development of gastro- and neuropathy, lesions of kidneys and liver, as well as the cardiovascular system, and the latter, in addition to serious side effects, lead to the development of steady resistance of pathogenic microorganisms and dysbacteriosis. This necessitates search for and development of new molecules with a wide range of therapeutic effects aimed to block the infectious and inflammatory process and to restore the functional ability of teeth in EPLs as much as possible (depending on a lesion severity). The aim of the study was to examine the anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats.

Materials and Methods: EPL simulation in experiments on the anesthetized rats was conducted in the following way: first, the pulp cavity of lower incisors was opened and left exposed to infection; then periodontal inflammation was induced using a ligature. Thirty days later, EPL developed in the animals. An N-isopropenylimidazole zinc metal complex derivative (laboratory code Pilim-1, prepared in form of gel), reference drug Metrogyl Denta® (M-D, dental gel), as well as the combination Pilim-1 + M-D were applied daily for 14 days on the lower incisors and appropriate gums, and also placed in the gingival pockets and pulp cavities, with pulp partially removed beforehands. After euthanasia of the animals on the 15th day of the experiments, gingival homogenates were assayed for the activity of elastase, urease, catalase, the level of malondialdehyde, and the antioxidant-prooxidant index was calculated, while pulp homogenates were assayed for the activity of elastase, urease, alkaline and acidic phosphatases, and the mineralizing index was calculated.

Results and Discussion: In the gum in EPL, Pilim-1 and, especially, the combination Pilim-1+M-D more significantly than M-D have a pronounced anti-inflammatory, antioxidant and antimicrobial (reduce a microbial content level) effects. In the pulp in EPL, Pilim-1 and, to a greater extent, the combination Pilim-1 + M-D in a more pronounced way than M-D have anti-inflammatory, antimicrobial (reduce a microbial content level) and mineralizing effects. In the therapeutic action mechanisms of Pilim-1 and, especially, the combination Pilim-1 + M-D in EPL conditions, their ability to have an antihypoxic effect and an inhibitory effect on cyclooxygenase and 5-lipoxygenase is likely to play a very important role, in addition to their identified effect on the examined metabolic processes. Besides, a certain role may be played by the presence of zinc and imidazole in the structure of Pilim-1, as they have a wide range of biological activity.

Conclusion: The presented results of studying Pilim-1 and its combination with M-D indicate their high therapeutic efficiency, especially when using the latter in the experimental EPL in rats, which makes it possible to consider Pilim-1 and Pilim-1 + M-D as potential therapeutic agents to treat EPL.

Graphical Abstract

Keywords:

antioxidant effect, N-isopropenylimidazole zinc metal complex derivative, microbial content, mineralizing effect, anti-inflammatory effect, endodontic-periodontal lesion

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Author Contribution

Pavel A. Galenko-Yaroshevsky, Kuban State Medical University

Pavel A. Galenko-Yaroshevsky, Corresponding member of the Russian Academy of Sciences, Doctor Habil. of Medical Sciences, Professor, Head of the Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: Galenko.Yaroсhevsky@gmail.com, ORCID ID: https://orcid.org/0000-0003-3190-1437. The author developed a concept, formed the idea and direction of research, developed and designed the methodology, and formulated the key goals and objectives.

Ivan I. Pavlyuchenko, Kuban State Medical University

Ivan I. Pavlyuchenko, Doctor Habil. of Medical Sciences, Professor, Head of the Department of Biology with the Course of Medical Genetics, Kuban State Medical University, Krasnodar, Russia; е-mail: inter-dekanat@mail.ru, ORCID ID: https://orcid.org/0000-0001-8019-9598. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Olga V. Shelemekh, Rostov State Medical University

Olga V. Shelemekh, graduate student of the Department of Dentistry No. 4, Rostov State Medical University, Rostov-on-Don, Russia; e-mail: lioli777@yandex.ru, ORCID ID: https://orcid.org/0000-0003-3488-9971. The author took part in conducting research, collection of primary data, their analysis, statistical processing and structuring the article.

Boris A. Trofimov, A.E. Favorsky Irkutsk Institute of Chemistry

Boris A. Trofimov, Doctor Habil. of Chemical Sciences, Professor, member of the Russian Academy of Sciences, Head of the Laboratory of Unsaturated Heteroatom Compounds, A.E. Favorsky Irkutsk Institute of Chemistry, Irkutsk, Russia; e-mail: boris_trofimov@irioch.irk.ru, ORCID ID: https://orcid.org/0000-0002-0430-3215. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Lidiya N. Parshina, A.E. Favorsky Irkutsk Institute of Chemistry

Lidiya N. Parshina, Doctor Habil. of Chemical Sciences, senior specialist of the Laboratory of Unsaturated Heteroatom Compounds, A.E. Favorsky Irkutsk Institute of Chemistry, Irkutsk, Irkutsk, Russia; e-mail: parshina@irioch.irk.ru, ORCID ID: https://orcid.org/0000-0002-5516-6214. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Viktor L. Popkov, Kuban State Medical University

Viktor L. Popkov, Doctor Habil. of Medical Sciences, Professor of the Department of Orthopedic Dentistry, Kuban State Medical University, Krasnodar, Russia; e-mail: vict.popkoff2015@yandex.ru, ORCID ID: https://orcid.org/0000-0001-7362-0073. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Svetlana A. Demyanenko, Medical Institute named after S.I. Georgievsky (winner of the Red Banner of Labor Award), V.I. Vernadsky Crimean Federal University

Svetlana A. Demyanenko, Doctor Habil. of Medical Sciences, Professor, Head of the Department of Dentistry and Orthodontics, Medical Institute named after S.I. Georgievsky (winner of the Red Banner of Labor Award), V.I. Vernadsky Crimean Federal University, Simferopol, Russia; e-mail: dc.kvalitet@gmail.com, ORCID ID: https://orcid.org/0000-0002-2743-498X. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Oleg V. Tsymbalov, Kuban State Medical University

Oleg V. Tsymbalov, Doctor Habil. of Medical Sciences, Professor, Professor of the Department of Surgical Dentistry and Maxillofacial Surgery, Kuban State Medical University, Krasnodar, Russia; e-mail: tsimbal_ov@mail.ru, ORCID ID: https://orcid.org/0000-0002-7970-323x. The author developed the key goals and objectives, conducted a critical review of the manuscript, analyzed it and provided valuable feedback.

Andrey V. Zadorozhniy, Rostov State Medical University

Andrey V. Zadorozhniy, Candidate of Medical Sciences, Associate Professor, Head of the Department of Dentistry No. 4, Rostov State Medical University, Rostov-on-Don, Russia; e-mail: stomvr1@gmail.com, ORCID ID: https://orcid.org/0000-0001-9552-8542. The author edited and prepared the text of the manuscript, was engaged in developing research design, providing the resources for the research: consumables, animals, tools, computer equipment for analysis – and correction of the final draft of the manuscript

Anait V. Zelenskaya, Kuban State Medical University

Anait V. Zelenskaya, Candidate of Medical Sciences, Associate Professor of the Pharmacology Department, Kuban State Medical University, Krasnodar, Russia; e-mail: anait_06@mail.ru, ORCID ID: https://orcid.org/0000-0001-9512-2526. The author participated in research design, analyzed and interpreted the research results; prepared and edited the text of the manuscript.

Irina B. Nektarevskaya, Rostov State Medical University

Irina B. Nektarevskaya, Candidate of Medical Sciences, Associate Professor of the Department of Dentistry No. 4, Rostov State Medical University, Rostov-on-Don, Russia; e-mail: nektir4546@mail.ru, ORCID ID: https://orcid.org/0009-0009-6733-9977. The author was engaged in conducting information retrieval research, animal handling and analysis of the obtained results.

Alina V. Sergeeva, Kuban State Medical University

Alina V. Sergeeva, teaching assistant, Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: alina_sergeeva_v@mail.ru, ORCID ID: https://orcid.org/0000-0003-4335-2156. The author was engaged in developing research design, conducting research; analysis and interpretation of the obtained data.

Nikolay E. Korovaykin, Kuban State Medical University

Nikolay E. Korovaykin, 3rd-year student, Department of General Medicine, Kuban State Medical University, Krasnodar, Russia; e-mail: nikkoro@bk.ru, ORCID ID: https://orcid.org/0009-0004-9543-7906. The author was engaged in developing research design, conducting research; analysis and interpretation of the obtained data.

Svetlana A. Lebedeva, Sechenov First Moscow State Medical University; RUDN University

Svetlana A. Lebedeva, Doctor Habil. of Biological Sciences, Associate Professor, Professor of the Department of Pharmacology, A.P. Nelyubin Institute of Pharmacy, Sechenov First Moscow State Medical University, Moscow, Russia; Department of Medical Elementology, RUDN University, Moscow, Russia; e-mail: Lebedeva502@yandex.ru, ORCID ID: https://orcid.org/0000-0001-8769-1040. The author developed the key goals and objectives, conducted a critical review of the manuscript and provided valuable feedback.

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11-11-2024

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Galenko-Yaroshevsky PA, Pavlyuchenko II, Shelemekh OV, Trofimov BA, Parshina LN, Popkov VL, Demyanenko SA, Tsymbalov OV, Zadorozhniy AV, Zelenskaya AV, Nektarevskaya IB, Sergeeva AV, Korovaykin NE, Lebedeva SA (2024) Study of anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats. Research Results in Pharmacology 10(4): 1–13. https://doi.org/10.18413/rrpharmacology.10.515

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Vol. 10 No. 4 (2024)

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Experimental Pharmacology

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Copyright (c) 2024 Galenko-Yaroshevsky PA, Pavlyuchenko II, Shelemekh OV, Trofimov BA, Parshina LN, Popkov VL, Demyanenko SA, Tsymbalov OV, Zadorozhniy AV, Zelenskaya AV, Nektarevskaya IB, Sergeeva AV, Korovaykin NE, Lebedeva SA

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