{"id":61301,"date":"2024-09-30T10:32:29","date_gmt":"2024-09-30T10:32:29","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=61301"},"modified":"2024-10-09T18:41:05","modified_gmt":"2024-10-09T18:41:05","slug":"the-effect-of-selenase-on-inflammatory-and-cytoprotective-markers-in-experimental-chronic-generalized-periodontitis","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no3\/the-effect-of-selenase-on-inflammatory-and-cytoprotective-markers-in-experimental-chronic-generalized-periodontitis\/","title":{"rendered":"The Effect of Selenase on Inflammatory and Cytoprotective Markers in Experimental Chronic Generalized Periodontitis"},"content":{"rendered":"\n

Introduction <\/strong><\/p>\n\n\n\n

Epidemiological studies conducted from 1990 to 2020 revealed a significant rise in patients with periodontal diseases leading to tooth loss. Thus, among the adult population of 17 countries, periodontitis was found in 62 %, and its severe form \u2013 in 23.6 %1<\/sup>. As international clinical trials show, the current therapeutic strategy for the treatment of periodontitis does not provide significant success2<\/sup>. Currently, medications obtained from various plant parts (bark, leaves, fruits, flowers, roots and rhizomes) are widely used in the treatment of periodontitis. The therapeutic effectiveness of essential oils that have anti-inflammatory, antibacterial, and wound-healing properties in inflammatory periodontal diseases, has been most studied3,4<\/sup>. Precious metal nanomaterials are also used in the treatment of periodontitis5,6<\/sup>. <\/p>\n\n\n\n

Oxidative stress is of great interest as a promising target in the treatment of periodontitis. Bacteria in inflamed gum tissue and virulence factors entering the bloodstream cause an exaggerated inflammatory response of the body. IL-1\u03b2 and TNF-\u03b1 stimulating signaling pathways such as NF-\u03baB (nuclear factor \u03ba-light-chain enhancer of activated B cells<\/em>), and mitogen-activated protein kinases, enhance the production of reactive oxygen species (ROS). Increased accumulation of ROS during periodontitis contributes to damage to DNA, proteins, and lipidss7,8<\/sup>. <\/p>\n\n\n\n

Herb extracts from medicinal plants with antioxidant activity such as bioflavonoids, carotenoids, organic acids, and polyphenols, are administered in periodontitis. However, practice shows that phytoantioxidants are not very effective due to low bioavailability and the peculiarity of the mechanism of antioxidant action9<\/sup>. Antioxidants such as melatonin, alpha-tocopherol, thiotriazoline, recombinant human superoxide dismutase (SOD), and mexidol have been shown to be effective in the treatment of periodontitis10-14<\/sup>. <\/p>\n\n\n\n

Selenium and selenium-containing compounds have\ninterested researchers and dentists worldwide owing to their promising\napplications in periodontitis. Selenium-based drugs have been found to have\nantioxidant, anti-inflammatory, cytoprotective properties, and are\nlow-toxic form of selenium15,16<\/sup>. <\/p>\n\n\n\n

Sodium selenite stimulates the conversion of methionine to cysteine, \u200b\u200band enhances glutathione synthesis. Due to its effect on cysteine-dependent domains, sodium selenite activates the expression of transcription factors such as p53 and NF-kB. Selenase exhibits cardio- and neuroprotective properties in myocardial infarction and cerebral ischemia. Selenase also has cardioprotective and neuroprotective action in myocardial infarction and cerebral ischemia32,42<\/sup>.   All of the above predetermined the topicality and prospects of this study. Our scientific activities were aimed at studying the healing efficacy of Selenase (Sodium selenite<\/em>), selenium-containing medication, under the conditions of modeling chronic generalized periodontitis CGP in rats by its effect on markers of inflammation and cytoprotection. <\/p>\n\n\n\n

Materials and Methods<\/strong><\/p>\n\n\n\n

The study was conducted on 40 adult female Wistar rats\n(weight 180-230 g). All experiments were conducted in accordance with national\nand international guidelines for the humane treatment of laboratory animals. 17,18<\/sup>. The\nBioethics Commission of ZDMPU confirmed compliance with ethical standards\n(Protocol No. 3, dated March 22, 2021).\nMaintenance of animals during the acclimatization period, and during the\nexperiment: rats were kept in accordance with the rules for the design,\nequipment and maintenance of vivaria. <\/p>\n\n\n\n

Experimental Model<\/strong><\/p>\n\n\n\n

Experimental CGP was simulated by a calcium-deficient peroxide diet for 8 weeks. Drinking water was replaced with a 2 % aqueous solution of calcium complexon disodium salt of ethylenediaminetetraacetic acid (Trilon B). In parallel, rats were administered Delagil<\/em> (Chloroquine phosphate<\/em>, produced by ICN Hungary S.A.) at a daily dose of 30 mg\/kg of body weight using a metal probe. Animals in the experiment received soft foods19 <\/sup>to reduce chewing function. Animals received the investigational drugs after CGP formation. The animals were divided into four groups, each with ten animals (n = 10): <\/p>\n\n\n\n

Group 1 \u2013 healthy animals (intact<\/em>),\nreceived normal saline solution (0.9 % NaCl) intragastrically for 30 days;<\/p>\n\n\n\n

Group 2 (control) \u2013 after introduction of\nchloroquine phosphate and Trilon B for 8 weeks, received 0.9 % NaCl\nintragastrically for 30 days; <\/p>\n\n\n\n

Group 3 \u2013 after introduction of chloroquine\nphosphate and Trilon B for 8 weeks, received Selenase 50 \u03bcg\/kg (Mivolis,\nGermany<\/em>) intragastrically using an atraumatic metal probe19<\/sup> for 30 days; <\/p>\n\n\n\n

Group 4 \u2013 after introduction of chloroquine phosphate and Trilon B for 8 weeks, received the reference medication Mexidol (Mexicor, PJSC \u201cTechnolog\u201d, Ukraine<\/em>) 250 mg\/kg intragastrically\ndaily14<\/sup> for 30 days. <\/p>\n\n\n\n

After 86 days of the study, blood was taken from the abdominal aorta\nafter laparotomy in anesthetized rats. (Sodium\nthiopental, 40 mg\/kg intraperitoneally<\/em>) using a special syringe. The\nobtained blood was subjected to centrifugation to obtain serum. To do this,\ntubes with blood were placed in the rotor cells of Eppendorf 5804R centrifuge\n(Germany) and centrifugation was carried out at +4\u00b0C, at 1500 rpm, 20 min. <\/p>\n\n\n\n

Levels of\nhypoxia inducible factor-1\u03b1 (HIF-1\u03b1) in the serum were assessed using the solid-phase\nsandwich enzyme-linked immunosorbent assay (ELISA) method. The ELISA Kit HIF-1\nalpha ELISA kit ab275103 (Abcam Limited, UK) was used according to the\ninstructions.  Levels of heat shock\nprotein 70 (HSP70<\/sub>) were calculated using the HSP70<\/sub> High-Sensitivity\nStressXpress ELISA Kit #MBS806878 (MyBioSource, Canada) according to the\ninstructions supplied with the kits. IL-1\u03b2 levels were calculated using the Rat\nInterleukin 1\u03b2 test, IL-1\u03b2 ELISA Kit #CSB-E08055r (CUSABIO TECHNOLOGY, USA)\naccording to the instructions supplied with the kits. <\/p>\n\n\n\n

The TNF-\u03b1\ncontent was determined with the Rat TNF alpha ELISA Kit #ab 108913 (Abcam, USA)\nin accordance with the instructions supplied with the kits. These analyses were\nconducted on a complete plate enzyme immunoassay analyzer (SIRIO-S, Seac,\nItaly).<\/p>\n\n\n\n

Statistical Analysis<\/strong><\/p>\n\n\n\n

Normality of distribution was analyzed using the Kolmogorov-Smirnov (D) and Lilliefors tests, and the Shapiro-Wilk (W) test14<\/sup>. In addition, the magnitude of asymmetry and excess of the data distribution were assessed as a criterion of agreement. If it was impossible to reject the null hypothesis about statistically significant differences in the distribution of variables from normal, nonparametric methods of data analysis were used. In other cases, parametric methods were used. If there were variants sharply deviated from the mass of observations, based on the properties of the standard normal distribution, these were excluded from further analysis if their absolute value was greater or less than the critical value, calculated as the sum of the sample mean and the triple sample of mathematical expectation value. Based on the properties of the standard normal distribution, variants that sharply deviate from the mass of observations, which in absolute value were greater or less than the critical value, calculated as the sum of the sample mean and the triple value of the sample mathematical expectation, were excluded from further analysis. Analysis of variance (ANOVA) was used to calculate independent variables in more than two samples. Data were presented as the mean and standard error of representativeness of the sample mean. Data processing and statistical analysis of the results were carried out using the statistical package of the licensed program “STATISTICA\u00ae for Windows 6.0” (StatSoft Inc., No. AXXR712D833214FAN5), as well as \u201cSPSS 16.0\u201d, \u201cMicrosoft Excel 2003\u201d. Statistical procedures and algorithms were performed in the form of specially written macros in the corresponding programs. Differences were judged as statistically significant if p-value was less than 0.05 for all analyses.<\/p>\n\n\n\n

Results  <\/strong><\/p>\n\n\n\n

Data presented in tables 1 and 2 show that an\n8-week administration of Chloroquine phosphate and Trilon B to rats led to\ntypical symptoms of periodontitis: hyperemia, swelling, and bleeding of the gums; mobility\nof teeth; and the formation of periodontal pockets up to 8 mm. A pronounced\nhealing effect characterized by a pronounced decrease in pocket depth to 4.6 mm;\nreduction of hyperemia, swelling and bleeding in rats with CGP taken Selenase.\nRats with CGP receiving Mexidol had a less pronounced healing effect compared to\nthe group receiving Selenase (Table 1). In animals of this group bleeding\npersisted when probing the periodontal pocket with a button probe; the depth of\nthe periodontal pocket was about 6 mm; swelling of the gums and mobility of\nteeth remained, but were less compared to the control group. <\/p>\n\n\n\n

Table 1: Concentration of IL-1\u03b2 and TNF-\u03b1 in the blood of rats with experimental CGP after administration of pharmacological medications<\/strong><\/p>\n\n\n\n\n\n\n\n\n
\n

Markers studied<\/strong><\/p>\n<\/td>\n

\n

Group 1<\/strong><\/p>\n

(n=10)<\/strong><\/p>\n<\/td>\n

\n

Group 2<\/strong><\/p>\n

 (n=10)<\/strong><\/p>\n<\/td>\n

\n

Group 3<\/strong><\/p>\n

 (n = 10)<\/strong><\/p>\n<\/td>\n

\n

Group 4<\/strong><\/p>\n

 (n = 10)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Periodontal pocket depth, mm<\/p>\n<\/td>\n

\n

0<\/p>\n<\/td>\n

\n

8.0 \u00b1 0.431<\/p>\n<\/td>\n

\n

4.6 \u00b1 0.691*<\/p>\n<\/td>\n

\n

6.0  \u00b1  0.931*<\/p>\n<\/td>\n<\/tr>\n

\n

IL-1\u03b2, ng\/mL<\/p>\n<\/td>\n

\n

0.13 \u00b1 0.014<\/p>\n<\/td>\n

\n

0.56 \u00b1 0.1091<\/sup><\/p>\n<\/td>\n

\n

0.31 \u00b1 0.028*1<\/sup><\/p>\n<\/td>\n

\n

0.397 \u00b1 0.061<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

TNF-\u03b1,  ng\/mL<\/p>\n<\/td>\n

\n

0.112 \u00b1 0.053<\/p>\n<\/td>\n

\n

0.907 \u00b1 0.1071<\/sup><\/p>\n<\/td>\n

\n

0.33 \u00b1 0.02*1#<\/sup><\/p>\n<\/td>\n

\n

0.577 \u00b1 0.03*1<\/sup><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Notes<\/em>: * \u2013 in comparison with the control group (CGP) (p < 0.05);<\/p>\n

1  <\/sup>\u2013 in comparison with the intact group (p < 0.05);<\/p>\n

#<\/sup> \u2013 in comparison with the Mexidol group (p < 0.05)<\/p>\n\n\n

Molecular studies of the peripheral blood of rats of the control group revealed pronounced elevation (several times<\/em>) of concentration of proinflammatory cytokines such as IL-1\u03b2 (p<0.05) and TNF-\u03b1 (p<0.05) in plasma in comparison with the intact group. <\/p>\n\n\n\n

The use of Selenase in rats with CGP contributed to a decrease in IL-1\u03b2\nby 44.6 % (p<0.05) and TNF-\u03b1 \u2013 by 65.9 % (p < 0.05) in comparison with\nthe control group. The use of Mexidol to rats with CGP contributed to the\ndecrease in the levels of TNF-\u03b1 by 36.3% (p < 0.05) compared to the control\ngroup without affecting the levels of IL-1\u03b2. As can be seen from the data in\nTable 1, Selenase was superior to Mexidol in reducing the levels of TNF-\u03b1. (p <\n0.05).<\/p>\n\n\n\n

The data characterizing the markers of\nendogenous cytoprotection HSP70<\/sub> and HIF-1\u03b1 presented in Table 2 show\nan increase in the levels of HSP70<\/sub> in rats with CGP by 1.4 times\ncompared to intact group, and the levels of HIF-1\u03b1 \u2013 by twice compared to the\nintact group. Administration of Selenase led to\nthe increase in the concentration of HIF-1\u03b1 by 36.8 % (p < 0.05) compared to\ncontrol group. Concentration of HSP70<\/sub> increased by 71.1 % compared\nto the control group, and by 138.0 % (p<0.05) compared to the intact group.\nThese statistically significant results indicate a remarkable action of\nselenase on HSP70<\/sub>-dependent mechanisms of endogenous cytoprotection. Administration of Mexidol contributed\nto the increase in HIF-1\u03b1 by 12.9 % (p < 0.05) in comparison with the\ncontrol group, without affecting the levels of HSP70<\/sub> in animals with\nCGP. <\/p>\n\n\n\n

Table 2:<\/strong> Concentration of HIF-1\u03b1 and HSP70<\/sub> in the blood of rats with experimental CGP after administration of pharmacological medications<\/strong><\/p>\n\n\n\n\n\n\n\n
\n

Markers<\/strong><\/p>\n

studied<\/strong><\/p>\n<\/td>\n

\n

Group 1<\/strong><\/p>\n

(n=10)<\/strong><\/p>\n<\/td>\n

\n

Group 2<\/strong><\/p>\n

(n=10)<\/strong><\/p>\n<\/td>\n

\n

Group 3<\/strong><\/p>\n

(n = 10)<\/strong><\/p>\n<\/td>\n

\n

Group 4<\/strong><\/p>\n

(n = 10)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

HIF-1\u03b1,<\/p>\n

pg\/ml<\/p>\n<\/td>\n

\n

1874.1 \u00b1 <\/strong>121.1<\/p>\n<\/td>\n

\n

2761.2 \u00b1 <\/strong>117.11<\/sup><\/p>\n<\/td>\n

\n

3778.3 \u00b1 109.2*1#<\/sup><\/p>\n<\/td>\n

\n

3117.5 \u00b1 <\/strong>112.3*1<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

HSP70, ng\/ml<\/p>\n<\/td>\n

\n

17.4 \u00b1 0.82<\/p>\n<\/td>\n

\n

24.2 \u00b1 1.321<\/sup><\/p>\n<\/td>\n

\n

41.4  \u00b1 4.22*1#<\/sup><\/p>\n<\/td>\n

\n

27.0 \u00b1 4,11<\/sup><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Notes<\/em>: * \u2013 compared to the control group (CGP) (p<0.05);<\/p>\n

1  <\/sup>\u2013 compared to the intact group (p<0.05);<\/p>\n

#<\/sup> \u2013 compared to the mexidol group (p <0.05)<\/p>\n\n\n

Discussion<\/strong><\/p>\n\n\n\n

The\nresults of the study indicate the development of a pronounced inflammatory\nprocess in the periodontium of animals with experimental CGP, which is also\nconfirmed by our early research14<\/sup>. \nThe results of the enzyme\nimmunoassay obtained in this work demonstrated changes in the levels of\nproinflammatory cytokines and cytoprotective factors during modeling of\nperiodontitis, which are in line with ideas about the pathogenesis of this\ndisease and do not contradict the data of other scientists21,22<\/sup>.<\/p>\n\n\n\n

Bacterial colonization of the surface of\nteeth and gum tissue leads to the initiation of inflammatory reactions that\ntrigger molecular mechanisms in periodontal degradation and the development of\nperiodontitis. Leukocytes release proinflammatory mediators that play an essential role in the progression of chronic\nperiodontitis in response to bacterial colonization. <\/p>\n\n\n\n

As a result of the\ndescribed events, the production of both pro-inflammatory cytokines such as\nIL-1\u03b1, IL-1\u03b2, IL-6, IL-12, and regulatory\ncytokines such as TNF-\u03b1, IL-4, IL-10 and IL-1RA increases. The increased\nproduction of chemokine interferon-inducible protein-10 (IP-10) is also\nnoted.  Marked expression of\npro-inflammatory cytokines against the background of increased levels of\nprostaglandin E2<\/sub>, interferon-\u03b3, and macrophage colony-stimulating\nfactor enhance osteoclast function and activate bone resorption23<\/sup>. <\/p>\n\n\n\n

IL-1\u03b2\npromotes the destruction of periodontal tissue, bone resorption and induces the\nproduction of proteinases that destroy bone tissue. TNF-\u03b1 and IL-1\u03b2 can trigger\nmolecular reactions leading to the activation of nitrosative and oxidative\nstress7<\/sup>. The bacterial cell and its\ncomponents, IL-1\u03b2 and TNF-\u03b1 enhance molecular activation mechanisms of\nhypersensitive polymorphonucleocytes involved in the production of ROS24<\/sup>.\nAnother source of ROS formation during periodontitis is neutrophil NADPH\noxidase, the activity of which increases during inflammation and correlates\nwith an increase in the levels of proinflammatory cytokines25<\/sup>. Pathological\nconcentrations of IL-1\u03b2 and TNF-\u03b1 enhance the expression of inducible nitric\noxide synthases (iNOS).  iNOS involved in the mechanisms of inflammation, the\nproduction of ROS, oxidative and nitrosative stress26,27<\/sup>. ROS, free\nradicals and stable products of oxidative stress (malondialdehyde, 4-hydroxy-2-transnonenal, etc<\/em>.) enhance the\nproduction of proinflammatory mediators, and gingival inflammation; reduce the\nexpression of antioxidant enzymes, HIF-1\u03b1, and contribute to alveolar bone\nloss. Many recent studies confirm a close relationship between the severity of\nperiodontitis and oxidative stress28-30<\/sup>. <\/p>\n\n\n\n

The increase in HSP70<\/sub> and HIF-1\u03b1\nin animals with CGP found in this study clearly corresponds to modern ideas about\ninflammatory periodontal diseases. IL-1, INF-\u03b3 and TNF-\u03b1 produced in inflamed\nperiodontal tissues function as triggers to induce HSP70<\/sub> production.\nLipopolysaccharides also increase hyperthermia-induced HSP70<\/sub> levels\nin monocyte\/macrophage cells. HSP70 <\/sub>expression levels correlate with\nIL-1\u03b2 levels in periodontitis. Increasing the production of HSP70<\/sub>\nprovides an anti-inflammatory effect, protection of cells from oxidative\nstress, and damage to bone matrix proteins in the initial stages of\nperiodontitis7,31<\/sup>. <\/p>\n\n\n\n

HSP70<\/sub> has\nantioxidant and anti-inflammatory effects, helps in early folding and refolding\nof proteins, protects the nucleus and lipid membrane from destruction, and\nprevents cell apoptosis32<\/sup>. HIF-1\u03b1, a major regulator of metabolism\nin periodontal tissue and alveolar bone, has critical functions in\nangiogenesis, erythropoiesis, energy metabolism, and cell fate determination\nduring inflammation. However, the role of this factor in the regulation of\ncytoprotection\/cytodestruction in chronic inflammation is not entirely clear\nand controversial33,34<\/sup>. The results\nof this research and our previous study7<\/sup> show a decrease in HIF-1\u03b1\ngene expression, and an increase in its expression in the protein level in experimental\nCGP. Apparently, changes in HIF-1\u03b1 expression depend on both the duration and\nseverity of the inflammatory response, and IL-1\u03b2 and TNF-\u03b1 modulate  its expression. In our case, a point at which\nthe production of HIF-1\u03b1 began to decrease, and the mechanisms of endogenous\ncytoprotection were disrupted, was reached. Many studies manifest both the\nstimulating effect of IL-1\u03b2 and TNF-\u03b1 on the synthesis of HIF-1\u03b135<\/sup>,\nand their inhibiting action on HIF-1\u03b1 expression36,37<\/sup>. The results\nobtained confirm the activation of endogenous cytoprotection mechanisms in\nresponse to inflammation in experimental CGP found in our earlier study14<\/sup>.<\/p>\n\n\n\n

The above justifies the use of antioxidants\nin complex drug therapy of periodontitis. Studies have shown the role of\nselenium in the body’s antioxidant defense, and the significance of its\ndeficiency in the development of periodontitis38-40<\/sup>. The protective\nproperties of selenase that we have identified in CGP can be explained from the\npoint of view of both the antioxidant properties of selenium, and its ability\nto influence HSP70<\/sub>-dependent mechanisms of endogenous cytoprotection. Thus, selenium can increase the\nexpression of glutathione peroxidase 4 (GPR-4), inhibit the oxidation of\nmembrane phospholipids, maintain the concentration of vitamin E, and regulate\nthe thiol-disulfide balance40-42<\/sup>. <\/p>\n\n\n\n

Selenium influences inflammation indirectly\nby regulating the expression of cyclooxygenase and lipoxygenase through the\nmitogen-activated protein kinase (MAPK) pathway43<\/sup>. Selenium can\npromote NF-\u03baB entry into the nucleus and bind to areas of\nantioxidant\/electrophilic regions of sensing elements (ARE\/EpRE) to enhance the\nexpression of antioxidant genes including GPx4, which reduces formation of\npro-inflammatory metabolites of arachidonic acid44<\/sup>. Selenase can\nincrease the expression of the endogenous cytoprotection factor HSP70<\/sub>\nby increasing the levels of reduced thiols, especially glutathione33,45<\/sup>.\nSelenium may influence cytoprotection mechanisms by regulating the levels of\nHIF-1\u03b1 through VHL-146<\/sup>. Selenium may also prolong the lifetime of\nHIF-1\u03b1 indirectly through HSP70<\/sub>34<\/sup>. <\/p>\n\n\n\n

It was found that Mexidol did not\nsignificantly affect the levels of IL-1\u03b2 in experimental CGP, but significantly\nlowered the expression of TNF-\u03b1, which may be due to the suppression of the\nexpression of the succinate receptor SUCNR1\/GPR9147<\/sup>. The mechanisms\nof the antioxidant effect of Mexidol do not provide it with action on the\nexpression of HSP70<\/sub> in animals with periodontitis. We identified a\ncertain effect of Mexidol on the synthesis of HIF-1\u03b1 in rats with CGP.\nApparently, Mexidol modulates the level of HIF-1\u03b1 through the succinate\nsignaling system48<\/sup>. Mexidol due to its antioxidant mechanisms\nimpedes the oxidative modification of macromolecules, providing\nmembrane-protective, antioxidant, and anti-inflammatory effects. Mexidol, due\nto the presence of a succinic acid residue in its structure, and inhibition of\nthe expression of the succinate receptors SUCNR1\/GPR91, reduces the levels of\npro-inflammatory cytokines, such as TNF-1\u03b147<\/sup>.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Based on the results of the\nstudy, it can be concluded that:<\/p>\n\n\n\n

Experimental CGP simulation in rats by 8-week administration of the prooxidant Delagil, and adding EDTA to water led to the development of typical symptoms of periodontitis: gum hyperemia, swelling, and bleeding; mobility of teeth; the formation of periodontal pockets up to 8 mm against the background of raised inflammatory markers IL-1\u03b2 and TNF-\u03b1, and molecular markers HIF-1\u03b1 and HSP70<\/sub>, indicating the homeostatic response of the periodontium in response to inflammation and subsequent hypoxia.  <\/p>\n\n\n\n

The course of treatment with a selenium derivative Selenase (50 mcg\/kg) in a therapeutic regimen to rats with CGP produced pronounced healing effects:  the reduction in the depth of periodontal pockets to 4.6 mm; cessation of bleeding; and disappearance of swelling against the backdrop of declining levels of inflammatory markers: IL-1\u03b2 \u2013 by 44.6 % (p < 0.05), and TNF-\u03b1 \u2013 by 65.9 % (p < 0.05) and compared to the group of untreated animals.<\/p>\n\n\n\n

The introduction of Selenase led to a rise in HIF-1\u03b1 by 36.8 % (p < 0.05); an increase in HSP70<\/sub> by 71.1 % in comparison with untreated animals; and by 138 % (p < 0.05) in comparison with the intact animals. These data indicate a strong effect of Selenase on HSP70<\/sub>-dependent mechanisms of endogenous cytoprotection.<\/p>\n\n\n\n

Selenase was significantly superior to the reference medication Mexidol in experimental CGP by its action on the studied parameters. <\/p>\n\n\n\n

The results obtained justify further study of Selenase as a promising treatment for CGP.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

The authors would like to acknowledge the Zaporizhzhia State Medical and Pharmaceutical University for providing some facilities in carrying out the research.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

The author(s) do not have any conflict of interest. <\/p>\n\n\n\n

Funding Source <\/strong><\/p>\n\n\n\n

The author(s) received no financial support for the research, authorship, and\/or publication of this article.<\/p>\n\n\n\n

Data Availability<\/strong><\/p>\n\n\n\n

The manuscript includes data obtained from the study.<\/p>\n\n\n\n

Ethics Statement<\/strong> <\/strong><\/p>\n\n\n\n

Experiments\nand all manipulations with animals were carried out in accordance with the\nregulations on the use of animals in biomedical experiments (Strasbourg, 1986,\nas amended in 1998) and the European Convention for the Protection of\nVertebrate Animals Used for Experimental and Scientific Purposes. The\nexperimental research protocols and their results were approved by the decision\nof the ZSMPhU Bioethics Commission.<\/p>\n\n\n\n

Informed Consent Statement<\/strong><\/p>\n\n\n\n

This study did not involve human participants, and therefore, informed consent was not required<\/p>\n\n\n\n

Authors\u2019 Contribution<\/strong><\/p>\n\n\n\n

Valerii Salnykov 1<\/sup>: collection\nand\/or assembly of data, writing the article, <\/p>\n\n\n\n

   Igor Belenichev2<\/sup>:\nresearch\nconcept and design, data analysis and interpretation, writing the article, critical\nrevision of the article<\/p>\n\n\n\n

Iryna Samura3 <\/sup>; data analysis and interpretation, writing the article, final approval of the article<\/p>\n\n\n\n

References <\/strong> <\/p>\n\n\n\n

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