The effect of zinc complex of N-isopropenylimidazole on the morphological characteristics of gum tissues in experimental endodontic-periodontal lesions in rats

Pavel A. Galenko-Yaroshevsky; Aleksandr А. Slavinskiy; Sergey S. Todorov; Viktor L. Popkov; Olga V. Shelemekh; Svetlana A. Lebedeva; Andrey V. Zadorozhniy; Anait V. Zelenskaya; Lusine O. Alukhanyan; Irina B. Nektarevskaya; Natalia D. Bunyatyan; Aleksandr А. Verevkin

doi:10.18413/rrpharmacology.9.10040

Authors

Pavel A. Galenko-Yaroshevsky Kuban State Medical University https://orcid.org/0000-0001-6856-1777
Aleksandr А. Slavinskiy Kuban State Medical University https://orcid.org/0000-0001-9824-9186
Sergey S. Todorov Rostov State Medical University Clinic https://orcid.org/0000-0001-8476-5606
Viktor L. Popkov Kuban State Medical University https://orcid.org/0000-0002-1955-9758
Olga V. Shelemekh Rostov State Medical University https://orcid.org/0000-0003-3488-9971
Svetlana A. Lebedeva I.M. Sechenov First Moscow State Medical University https://orcid.org/0000-0001-8769-1040
Andrey V. Zadorozhniy Rostov State Medical University https://orcid.org/0000-0001-9552-8542
Anait V. Zelenskaya Kuban State Medical University https://orcid.org/0000-0001-9512-2526
Lusine O. Alukhanyan Kuban State Medical University https://orcid.org/0009-0005-1752-2491
Irina B. Nektarevskaya Rostov State Medical University https://orcid.org/0009-0009-6733-9977
Natalia D. Bunyatyan I.M. Sechenov First Moscow State Medical University; Scientific Centre for Expert Evaluation of Medicinal Products https://orcid.org/0000-0001-9466-1261
Aleksandr А. Verevkin Kuban State Medical University https://orcid.org/0000-0002-4159-2618

DOI:

https://doi.org/10.18413/rrpharmacology.9.10040

Abstract

Introduction: Combined inflammatory and destructive processes affecting the dental pulp and tissues of the periodontal complex are among the most problem diseases of the dental system. Current therapy with use of available pharmacological agents does not always allow achieving the expected positive result. In addition, often the lack of information about morphological processes in the tissues of the dental system, in particular the gums, with endodontic-periodontal lesion (EPL) limits the ability of dentists to carry out targeted pharmacotherapy with both traditional and, in particular, new medications. The aim of the study was to evaluate the morphological characteristics of gum tissues in a therapeutic context of N-isopropenylimidazole zinc complex derivative in experimental endodontic-periodontal lesion in rats.

Materials and Methods: A simulation of EPL in rats was performed in two ways: simultaneous induction of acute periodontitis and parodontitis by pulp extraction and natural infection of the pulp cavity, as well as by ligation of the necks of lower incisors. The research protocols included 5 groups of animals: 1^st – intact group (control-1); 2^nd – animals with simulated EPL (control-2); 3^rd – animals with simulated EPL and treated with Metrogyl Denta^® gel (M-D); 4^th – animals with simulated EPL and treated with N–isopropenylimidazole zinc complex derivative gel under the laboratory code Pilim-1; and 5^th – animals with simulated EPL and treated with the combination of M-D + Pilim-1. The gum of the lower incisors was taken for morphological studies. Slides were stained with hematoxylin and eosin. Computer morphometry was performed using the ImageJ software.

Results and Discussion: The substances M-D, Pilim-1 and, especially, the combination of M-D+Pilim-1 (against the background of chlorhexidine bigluconate used as oral rinse) for 14 days in rats with simulated EPL cause a significant improvement of the morphological structure of the gum with minimal residual dystrophy and sclerosis. The combination M-D + Pilim-1 led to a 1.3-time increase in epithelial thickness, and a 1.5-time decrease in acanthosis depth in comparison with M-D, while the number of capillaries and their diameter had no significant differences. Compared with Pilim-1, the epithelial thickness increased 1.5 times, and the acanthosis depth and the number of capillaries decreased 1.6 and 1.4 times, respectively, whereas the diameter of the capillaries did not change significantly. The pronounced protective effect of the combination M-D + Pilim-1 on the morphological structure of the gingival mucosa of rats with simulated EPL may be associated with antimicrobial, anti-inflammatory, regenerating, angioprotective and antioxidant properties of both M-D and Pilim-1 separately, and, possibly to a greater extent, of the combination M-D + Pilim-1.

Conclusion: The substances M-D, Pilim-1 and, especially, the combination M-D + Pilim-1 (against the background of chlorhexidine bigluconate used as oral rinse) for 14 days in rats with simulated EPL have a protective effect on the epithelial structure and the connective tissue of the proper mucous plate, manifested in active normalization of pathological changes and significant restoration of their organotypic structure.

Graphical Abstract

Keywords:

computer morphometry, N-isopropenylimidazole zinc complex derivative, Metrogyl Denta®, pathomorphological changes in gum tissues, experimental endodontic-periodontal lesions in rats

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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; Senior Research Scientist of Research Institute for the Pharmacology of Living Systems of Belgorod State National Research University, Belgorod, Russia; е-mail: Galenko.Yaroсhevsky@gmail.com; ORCID ID https://orсid.org/0000-0001-6856-1777. The author’s contribution: concept development – conceptualization and direction development of the research; generation of key aims and objectives.

Aleksandr А. Slavinskiy, Kuban State Medical University

Holder of Advanced Doctorate (Doctor Habil. of Science) in Biological Sciences, Professor, Head of the Department of Pathological Anatomy of Kuban State Medical University, Krasnodar, Russia; е-mail: al-slavinsky@mail.ru; ORCID ID https://orcid.org/0000-0001-9824-9186. The author’s contribution: defining the key aims and objectives; interpretation of the data obtained; critical revision of the manuscript, providing valuable comments.

Sergey S. Todorov, Rostov State Medical University Clinic

Holder of Advanced Doctorate (Doctor Habil.) of Science) in Medical Sciences; pathoanatomist, Head of the Morphological Department of Rostov State Medical University Clinic, Rostov-on-Don, Russia; e-mail: sertodorov@gmail.com; ORCID ID https://orcid.org/0000-0001-8476-5606. Author's contribution: development of key aims and objectives; preparation of histological material (rat samples) for examination; analysis and interpretation of the data obtained; drafting of the manuscript and its editorial revision.

Viktor L. Popkov, Kuban State Medical University

Viktor L. Popkov, 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/0000-0002-1955-9758. The author’s contribution: development and design of methodology, defining the key aims and objectives, critical revision of the manuscript and its analysis, providing valuable comments.

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: data collection and analysis, sampling of the biopsy material, correction of micrographs, statistical data processing and compilation of the manuscript.

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.

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 ID https://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; approval of the final version of the article.

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://orсid.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.

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://orсid.org/0009-0005-1752-2491. Author's contribution: experimentation; analysis and interpretation of research results; participation in scientific design.

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://orсid.org/0009-0009-6733-9977. Author's contribution: search for and analysis of information; animal keeping control, preparation and sampling of material for research; participation in the analysis of the research results.

Natalia D. Bunyatyan, I.M. Sechenov First Moscow State Medical University; Scientific Centre for Expert Evaluation of Medicinal Products

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; 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://orсid.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.

Aleksandr А. Verevkin, Kuban State Medical University

PhD in Medical Sciences, Associate Professor of the Department of Pathological Anatomy of Kuban State Medical University, Krasnodar, Russia; e-mail: vilehand@bk.ru; ORCID ID https://orcid.org/0000-0002-4159-2618. Author's contribution: computer morphometry; analysis and interpretation of research results.