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

Authors

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: 1st – intact group (control-1); 2nd – animals with simulated EPL (control-2); 3rd – animals with simulated EPL and treated with Metrogyl Denta® gel (M-D); 4th – animals with simulated EPL and treated with N–isopropenylimidazole zinc complex derivative gel under the laboratory code Pilim-1; and 5th – 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

References

Ardila C-M, Bedoya-García J-A (2022) Clinical and microbiological efficacy of adjunctive systemic quinolones to mechanical therapy in periodontitis: a systematic review of the literature. International Journal of Dentistry 2022: 4334269. https://doi.org/10.1155/2022/4334269 [PubMed] [PMC]

Çirakoğlu N, Karayürek F (2021) Knowledge and awareness levels of dentists’ about the endo-perio lesions: the questionnaire-based research. Adiyaman Üniversitesi Sağlık Bilimleri Dergisi 7(1): 64–70. https://doi.org/10.30569/adiyamansaglik.815597

Denisova YuL, Dedova LN (2021) Endoperiodontal lesions: new evidence for predicting endoperiodontitis. Dentist [Stomatolog] 2(41): 8–12. https://doi.org/10.32993/dentist.2021.2(41).6 [in Russian]

Dierichs L, Kloubert V, Rink L (2018) Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages. European Journal of Nutrition 57(6): 2161–2169. https://doi.org/10.1007/s00394-017-1491-2 [PubMed]

Elgezawi M, Haridy R, Almas K, Abdalla MA, Omar O, Abuohashish H, Elembaby A, Wölfle UC, Siddiqui Y, Kaisarly D (2022) Matrix metalloproteinases in dental and periodontal tissues and their current inhibitors: developmental, degradational and pathological aspects. International Journal of Molecular Sciences 23(16): 8929. https://doi.org/10.3390/ijms23168929 [PubMed] [PMC]

Galenko-Yaroshevsky PA, Slavinskiy AА, Zadorozhniy MA, Leontev VK, Kheigetyan AV, Popkov VL, Zelenskaya AV, Chuprinenko LM, Verevkin AА, Lomsadze IG, Materenchuk MYu, Lebedeva SA (2023) Pathomorphological analysis of the gum tissues in the application of the combination of Soderm-Forte gel with Cytoflavin. Research Results in Pharmacology 9(2): 1–10. https://doi.org/10.18413/rrpharmacology.9.10017

Grudyanov AI, Makeeva MK, Pyatigorskaya NV (2013) Modern concepts of etiology, pathogenesis and treatment approaches to endo-perio lesions. Annals of the Russian Academy of Medical Sciences [Vestnik Rossiijskoij Akademii Meditscinskikh Nauk] 68(8): 34–36. https://doi.org/10.15690/vramn.v68i8.721 [in Russian]

Grudyanov AI. (2022) Periodontal Ddiseases: an eEducational and mMethodological gGuide (2nd ed.ition). MIA, Moscow, MIA, 416 pp. [in Russian]

Guerra M, Carvalho NB, Santos S, Nascimento MT, Sá R, Carvalho AM, Carvalho EM, Carvalho LP (2022) TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals. Frontiers in Immunology 13: 954103. [PubMed] [PMC]

Gushchin YA, Kvanchiani VV (2020) Comparative morphology of the oral cavity in experimental animals and humans. Laboratory Animals for Science [Laboratornye Zhivotnye dlya Nauchnykh Issledovaniji] 1: 9–22. https://doi.org/10.29296/2618723X-2020-01-02 [in Russian]

Harrington GW (1979) The perio-endo question: Differential diagnosis. Dental Clinics of North America 23(4): 673–690.[PubMed]

Kade AH, Turovaja AYu, Trofimenko AI, Sidorenko AN, Petrosyan YeA, Tsymbalov OV, Uvarova EA, Tarasova SR, Efremenko AV, Unanyan KG, Myasnikova VV (2016) The elaboration of model of acute periodontitis in the experiment on rats. Kuban Scientific Medical Bulletin [Kubanskiij Nauchnyyj Medictsinskij Vestnik] 6: 77–80. https://doi.org/10.25207/1608-6228-2016-6-77-80 [in Russian]

Keles GC, Acikgoz G, Ayas B, Sakallioglu E, Firatli E (2005) Determination of systemically and locally induced periodontal defects in rats. The Indian Journal of Medical Research 121(3): 176–184 [PubMed]

Lebedeva SA, Galenko-Yaroshevsky PA (Jr.), Melnik SI, Kozin SV, Demura TA, Arshinov JR, Gulevskaya ON, Galenko-Yaroshevsky PA (2021) Evaluation of the wound-healing effect of an N-isopropenylimidazole zinc metal complex derivative on a linear skin wound model in rats. Pharmacy [Farmatsciya] 70 (6): 49–56. [in Russian]

Lebedeva SA, Galenko-Yaroshevsky PA (Jr.), Melnik SI, Kozin SV, Demura TA, Arshinov YaR, Svistakova MV, Grigorevskikh EM, Galenko-Yaroshevsky PA (2022) Wound healing effect of organometallic zinc complex in the rat model of planar skin wound. Research Results in Biomedicine [Nauchnye Rezul’'taty Biomedictsinskikh Issledovanij] 8(1): 71–81. https://doi.org/10.18413/2658-6533-2022-8-1-0-5 [in Russian]

Lebedeva SA, Galenko-Yaroshevsky PA (Jr.), Samsonov MYu, Erlich AB, Margaryan AG, Materenchuk MYu, Arshinov IaR, Zharov YuV, Zelenskaya AV, Shelemekh OV, Lomsadze IG, Demura TA (2023) Molecular mechanisms of wound healing: the role of zinc as an essential microelement. Research Results in Pharmacology 9(1): 25–39.https://doi.org/10.18413/rrpharmacology.9.10003

Malinina EI, Mazalova MV (2020) Alkaline phosphatase in neurological practice (review). Medical Anthology [Medictsinskiji Al’ʹmanakh] 4 (65): 21–28. [in Russian]

Miklyaev SV, Leonova OM (2019) Endodonto-periodontal lesions (literature review). Colloquium-Journal 5(29): 18–19.https://doi.org/10.24411/2520-6990-2019-10066

Mironov AN (2012) Guidelines for Pre-clinical Trials of Medicines. Grif and K, Moscow, Grif and K, 944 pp. [in Russian]

Moiseev DA, Volkov SI, Konov AA, Kulyukina MA (2021) The morphological and functional relationship between dental pulp and periodontal tissue in the aspect of endo-perio lesions. Periodontology [Parodontologiya] 26(4): 289–299.https://doi.org/10.33925/1683-3759-2021-26-4-289-299 [in Russian]

Moroz PV, Iordishvili AK (2019) Combined lesion of endodont and periodontal in adults and its causes. Endodontology Today [Endodontologiya Segodnya] 17(2): 41–46. https://doi.org/10.33925/1683-2981-2019-17-2-41-46 [in Russian]

Nemcovsky CE, Calvo Guirado JL, Moses O (2019) Periodontal aspects of endodontic-periodontal lesions. Clinical Dentistry Reviewed 3(1): 5. https://doi.org/10.1007/s41894-019-0044-x

Orekhova LYu, Atrushkevitch VG, Loboda ES, Vashneva VYu, Petrov AA (2021) Current antibiotic therapy of endo-perio lesions with secondary endodontic involvement. Periodontology [Parodontologiya] 26(2): 105–113. https://doi.org/10.33925/1683-3759-2021-26-2-105-113 [in Russian]

Polson AM, Zander HA (1983) Effect of periodontal trauma upon intraboni pockets. Jоurnal of Periodontology 54(10): 586–591. https://doi.org/10.1902/jop.1983.54.10.586 [PubMed]

Popkov VL, Tseluyko KV, Leontyev VK, Zadorozhny AV, Kheygetyan AV, Zadorozhny MA, Galenko-Yaroshevsky PA (2022) Influence of pharmacological composition with gel, containing superoxide dismutase and silver nanocluster monomers, and recombinant human superoxide dismutase on blood microcirculation in the gums of rats under experimental pathology. International Dental Review [Stomatologiya Dlya Vsekh] 100(3): 53–59.https://doi.org/10.35556/idr-2022-3(100)53-59 [in Russian]

Prasad AS (2020) Lessons learned from experimental human model of zinc deficiency. Journal of Immunology Research 2020: 9207279. https://doi.org/10.1155/2020/9207279 [PubMed] [PMC]

Salesa B, Sabater I Serra R, Serrano-Aroca Á (2021) Zinc chloride: time-dependent cytotoxicity, proliferation and promotion of glycoprotein synthesis and antioxidant gene expression in human keratinocytes. Biology 10(11): 1072. https://doi.org/10.3390/biology10111072 [PubMed] [PMC]

Saroch N (2021) Periobasics: A tTextbook of Periodontics and Implantology. Solan, Sushrut Publications Private Limited, 1160 pp.

Shakhmardanova SA, Galenko-Yaroshevsky PA (2017) N-alkenylimidazole metal complex derivatives as effective agents for the hypoxic conditions. Research Result: Pharmacology and Clinical Pharmacology 3(1): 49–72. https://doi.org/10.18413/2500-235X-2017-3-1-49-72

Shakhmardanova SA, Parshina LN, Trofimov BA, Galenko-Yaroshevsky PA, Tarasov VV, Maksimov ML, Sologova SS (2016) Antihypoxic activity of zinc acetate complexes with N-allenyl- and N-isopropenylimidazoles on hypoxia models of various ethiology. Sechenov Medical Journal [Sechenovskiij Vestnik] 3(25): 46–50. [in Russian]

Slavinskiy AA, Verevkin AA (2022) Computer analysis of inflammatory infiltrate in the diagnosis of heart transplant rejection. Russian Journal of Transplantology and Artificial Organs [Vestnik Transplantologii i Iskusstvennykh Organov] 24(S): 167. [in Russian]

Turovaya AYu, Kade AKh, Gubareva EA, Uvarov AV, Zanin SA, Murzin IG, Arakelyan YuL (2010) Acute periodontitis experimental modeling in rats. Fundamental Research [Fundamental’'nye Issledovaniya] 10: 46–50. [in Russian]

Veber VR, Okovitiy SV, Trezubov VN, Selizarova NO (2021) Clinical pPharmacology for dDentists: textbook. GEOTAR-MEDIA, Moscow, GEOTAR-MEDIA, 352 pp. https://doi.org/10.33029/9704-5735-1-KFS-2021-1-352 [in Russian]

Yanushevich OO, Dmitrieva LA (2018) Periodontology. National manual. GEOTAR-MEDIA, Moscow, GEOTAR-MEDIA, 752 pp. [in Russian]

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.

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Published

04-10-2023

How to Cite

Galenko-Yaroshevsky PA, Slavinskiy AА, Todorov SS, Popkov VL, Shelemekh OV, Lebedeva SA, Zadorozhniy AV, Zelenskaya AV, Alukhanyan LO, Nektarevskaya IB, Bunyatyan ND, Verevkin AА (2023) The effect of zinc complex of N-isopropenylimidazole on the morphological characteristics of gum tissues in experimental endodontic-periodontal lesions in rats. Research Results in Pharmacology 9(4): 1–12. https://doi.org/10.18413/rrpharmacology.9.10040

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Experimental Pharmacology

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