Preclinical evaluation of a gel composition based on a flavonoid complex for the treatment of periodontal diseases in orthodontic patients
DOI:
https://doi.org/10.14739/2310-1210.2023.4.274894Keywords:
experiment, laboratory animals, periodontal gel composition, flavonoids, toxicological studies, sensitization, lipid peroxidation, orthodontic patientsAbstract
The aim of the work was a preclinical assessment of acute toxicity, skin resorptive, irritant effects, cumulative and catalase activity, as well as sensitizing properties of the local gel composition “Benzidaflaziverdine” (GCB) used for the treatment of periodontal diseases in orthodontic patients.
Materials and methods. 119 animals were involved in the experiment, assigned to seven main and two control groups. GCB was administered intragastrically in doses of 300–600 mg/kg and intradermally of 200 μg into the outer surface of the ear. The native solution of GCB was applied to the skin and mucous membranes, administered orally by the method of “subchronic toxicity” and to the surface of the chorioallantoic membrane (CAM) of chicken embryos. The intensity of lipid peroxidation (LPO) was assessed by the level of diene conjugates (DCs) and malondialdehyde (MDA), and the antioxidant system by catalase activity. The specific leukocyte agglomeration reaction (SLAR), the specific leukocyte lysis reaction, and neutrophil damage indicators were used.
Results. The median lethal dose LD50 for rats and mice of both sexes exceeded 5000 mg/kg. The irritant effect of GCB on the mucous membranes was manifested by hyperemia on the second day. Symptoms of irritation disappeared after 3–4 days without medical intervention. An analysis of the CAM blood vessels after exposure to GCB in two observations at the 120th second showed the beginning of hemorrhages. In one observation, GCB caused minor hemorrhages at the 300th second of the experiment.
It was found that the coefficient of GCB irritant action was 5 (the mean score of Me (Q1; Q3) was 5 (4; 5)). The coefficient of cumulation (Kcum) exceeded 8.2. An insignificant increase in the median or mean values of catalase enzyme activity, DCs, and the amount of LPO end product such as MDA was observed compared to the control group animals. The SLAR test indicated the development of a delayed-type allergic reaction under the influence of GCB in a 1:10 dilution. One-hundred-fold dilution did not cause significant changes in the indicator in the main group compared to the control one.
Conclusions. GCB belongs to the 4th class of toxicity – practically non-toxic substances, does not have sex- and species sensitivity, has weak cumulative activity, minimal effect on the system of LPO. GCB can be recommended for the use in clinical periodontology for medical support of orthodontic patients.
References
Pini Prato, G. P., & Chambrone, L. (2020). Orthodontic treatment in periodontal patients: The use of periodontal gold standards to overcome the "grey zone". Journal of periodontology, 91(4), 437-441. https://doi.org/10.1002/JPER.19-0306
Reynolds, I., & Duane, B. (2018). Periodontal disease has an impact on patients' quality of life. Evidence-based dentistry, 19(1), 14-15. https://doi.org/10.1038/sj.ebd.6401287
Danko, E. M., Panto, V. V. & Nesterenko, M. L. (2022). Otsinka faktoriv ryzyku u patsiientiv iz zakhvoriuvanniamy tkanyn parodonta [Evaluation of risk factors in patients with periodontal tissue diseases]. Visnyk problem biolohii i medytsyny - Bulletin of problems biology and medicine, (2Suppl), 81-82. [in Ukrainian]. https://doi.org/10.29254/2077-4214-2022-2-164/addition-81-82
Li, Y., Zhan, Q., Bao, M., Yi, J., & Li, Y. (2021). Biomechanical and biological responses of periodontium in orthodontic tooth movement: up-date in a new decade. International journal of oral science, 13(1), 20. https://doi.org/10.1038/s41368-021-00125-5.
Sczepanik, F. S. C., Grossi, M. L., Casati, M., Goldberg, M., Glogauer, M., Fine, N., & Tenenbaum, H. C. (2020). Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way. Periodontology 2000, 84(1), 45-68. https://doi.org/10.1111/prd.12342
López-Mateos, C. M., López-Mateos, M. L. M., Aguilar-Salvatierra, A., Gómez-Moreno, G., Carreño, J. C., Khaldy, H., & Menéndez-Núñez, M. (2022). Salivary Markers of Oxidative Stress in Patients Undergoing Orthodontic Treatment with Clear Aligners versus Self-Ligating Brackets: A Non-Randomized Clinical Trial. Journal of Clinical Medicine, 11(12). https://doi.org/10.3390/jcm11123531
Zeng, Y., Song, J., Zhang, M., Wang, H., Zhang, Y., & Suo, H. (2020). Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures. Antioxidants (Basel, Switzerland), 9(8), 732. https://doi.org/10.3390/antiox9080732
Abou Baker, D. H. (2022). An ethnopharmacological review on the therapeutical properties of flavonoids and their mechanisms of actions: A comprehensive review based on up to date knowledge. Toxicology reports, 9, 445-469. https://doi.org/10.1016/j.toxrep.2022.03.011
Hodovanyi, O. V., Hodovana, O. I., Shandra, M. S., Kliuchivska, O. Yu., & Stoika, R. S. (2022). Zasib u formi helevoi kompozytsii "Benzydaflaziverdyn" z prolonhovanoiu diieiu dlia likuvannia zakhvoriuvan tkanyn parodonta (Patent Ukrainy na vynakhid No. 125272) [Remedy in the form of a gel composition "Benzidaflaziverdine" with a prolonged action for the treatment of periodontal tissue diseases. Ukraine Patent UA No. 125272)]. https://sis.ukrpatent.org/en/search/detail/1677320/
Ministry of Health of Ukraine. (1999, July 1). Derzhavni sanitarni pravyla i normy bezpeky produktsii parfumerno-kosmetychnoi promyslovosti [State sanitary rules and product safety standards of the perfumery and cosmetics industry (No. 27)]. https://zakon.rada.gov.ua/rada/show/v0027588-99#Text
Zadorozhna, H. O., & Khomenko, O. M. (2019). Metodychnyi posibnyk dlia vykonannia eksperymentalnykh robit iz vykorystanniam shchuriv [Methodical guide for conducting experimental works with the use of rats]. Dnipro. [in Ukrainian]. https://www.biochemistry-dnu.dp.ua/wp-content/downloads/metodichki/eksper-rob-z-vykor-schuriv.pdf
Directive 2010/63. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. https://eur-lex.europa.eu/eli/dir/2010/63/2019-06-26
Maksymenko, Yu., & Vyskushenko, D. (2022). Bioetyka ta biobezpeka [Bioethics and biosafety]. Zhytomyr. [in Ukrainian].
Gutiérrez-Sánchez, M., Romero-Castro, A., Correa-Basurto, J., Rosales-Hernández, M. C., Padilla-Martínez, I. I., & Mendieta-Wejebe, J. E. (2021). Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity. Molecules (Basel, Switzerland), 26(22), 6801. https://doi.org/10.3390/molecules26226801
Pinheiro, A. C., Ombredane, A. S., Pinheiro, W. O., Andrade, L. R., Silva, V. R. P., Felice, G. J., Alves, D. S., Albernaz, A. F., Silveira, A. P., Lima, M. C. F., Veiga-Junior, V. F., Gomes, T. F. S., Damasceno, E. A. M., Veiga-Souza, F. H., Souza, P. E. N., Báo, S. N., Duarte, E. C. B., Carneiro, M. L. B., Azevedo, R. B., Funez, M. I., … Joanitti, G. A. (2022). Evaluation of Biocompatibility, Anti-Inflammatory, and Antinociceptive Activities of Pequi Oil-Based Nanoemulsions in In Vitro and In Vivo Models. Nanomaterials (Basel, Switzerland), 12(23), 4260. https://doi.org/10.3390/nano12234260
Fraguas-Sánchez, A. I., Martín-Sabroso, C., & Torres-Suárez, A. I. (2022). The Chick Embryo Chorioallantoic Membrane Model: A Research Approach for Ex Vivo and In Vivo Experiments. Current medicinal chemistry, 29(10), 1702-1717. https://doi.org/10.2174/0929867328666210625105438
Lim, M. K., Kim, J. Y., Jeong, J., Han, E. H., Lee, S. H., Lee, S., Kim, S. D., & Lee, J. (2021). Evaluation of Subchronic Toxicity and Genotoxicity of Ethanolic Extract of Aster glehni Leaves and Stems. Evidence-based complementary and alternative medicine : eCAM, 2021, 1018101. https://doi.org/10.1155/2021/1018101
Murugan, S., Solanki, H., Purusothaman, D., Bethapudi, B., Ravalji, M., & Mundkinajeddu, D. (2021). Safety Evaluation of Standardized Extract of Curcuma longa (NR-INF-02): A 90-Day Subchronic Oral Toxicity Study in Rats. BioMed research international, 2021, 6671853. https://doi.org/10.1155/2021/6671853
Sirman, Y. V., Savytskyi, I. V., & Preis, N. I. (2020). Dynamika rivniu malonovoho dialdehidu pry eksperymentalnii diabetychnii retynopatii ta sposobakh yii korektsii [Dynamics of the malondialdehyde levels in experimental diabetic retinopathy and methods of itscorrection]. Aktualni problemy suchasnoi medytsyny, 20(4), 95-100. [in Ukrainian].
Tang, Q., Su, Y. W., & Xian, C. J. (2019). Determining Oxidative Damage by Lipid Peroxidation Assay in Rat Serum. Bio-protocol, 9(12), e3263. https://doi.org/10.21769/BioProtoc.3263
Chukwuebuka, N. B., Elias, D. T. M., Ijego, A. E., Peggy, O. E., Ejime, A. C., Omeru, O., Yabrade T., Eke Chidinma N., & Ikemefune, E. E. (2021). Changes in Antioxidant Enzymes Activities and Lipid Peroxidase Level in Tissues of Stress-induced Rats. Biomedical and Pharmacology Journal, 14(2), 583-596. https://doi.org/10.13005/bpj/2161
Barbaud, A., Weinborn, M., Garvey, L. H., Testi, S., Kvedariene, V., Bavbek, S., Mosbech, H., Gomes, E., Aberer, W., Elberink, H. N. G. O., Torres, M. J., Ponvert, C., Ayav, C., Gooi, J., & Brockow, K. (2020). Intradermal Tests With Drugs: An Approach to Standardization. Frontiers in medicine, 7, 156. https://doi.org/10.3389/fmed.2020.00156
Laposata, M. (Eds.). (2018). Laposata's Laboratory Medicine Diagnosis of Disease in Clinical Laboratory. New York: McGraw Hill/Medical.
Welsby, P. D., & Weatherall, M. (2022). Statistics: an introduction to basic principles. Postgraduate medical journal, 98(1164), 793-798. https://doi.org/10.1136/postgradmedj-2020-139446
Passali, D., Barat, V., Cadevall, O., Freire, H. M., Grattagliano, I., Gutu, I., Mösges, R., & Pavlysh, A. (2022). International Delphi-based consensus on the appropriate use and effect of Benzydamine hydrochloride in the treatment of sore throat. BMC primary care, 23(1), 296. https://doi.org/10.1186/s12875-022-01901-w
Beketova, G., Kuznetsova, L., Grynevych, O., Broun, T., Momotiuk, L., Motuzka, O., & Yashchenko, L. (2021). Analysis of the clinical trial results of the flavonoid effects on some cellular immunity indicators in children and adults. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 49(289), 44-53.
Matyash, V., Grynevych, O., & Broun, T. (2019). PROTEFLAZID®: clinical studies as evidence base of its antiviral activity. Polski merkuriusz lekarski, 46(271), 30-31.
Marincak Vrankova, Z., Rousi, M., Cvanova, M., Gachova, D., Ruzicka, F., Hola, V., Lochman J., Izakovicova Holla L., Brysova A., & Borilova Linhartova, P. (2022). Effect of fixed orthodontic appliances on gingival status and oral microbiota: a pilot study. BMC Oral Health, 22(1). https://doi.org/10.1186/s12903-022-02511-9
Primožič, J., Poljšak, B., Jamnik, P., Kovač, V., Čanadi Jurešić, G., & Spalj, S. (2021). Risk Assessment of Oxidative Stress Induced by Metal Ions Released from Fixed Orthodontic Appliances during Treatment and Indications for Supportive Antioxidant Therapy: A Narrative Review. Antioxidants (Basel, Switzerland), 10(9), 1359. https://doi.org/10.3390/antiox10091359
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
