scholarly journals SYNERGISTIC EFFECT OF QUERCETIN AND EPIGALLOCATECHIN-3-GALLATE AS AGENTS TO PREVENT CONNECTIVE TISSUE DISINTEGRATION IN THE PERIODONTIUM OF RATS UNDER SYSTEMIC AND LOCAL ADMINISTRATION OF LIPOPOLISACCHARIDE OF SALMONELLA TYPHI

2019 ◽  
Vol 23 (5-6) ◽  
pp. 42-44
Author(s):  
A.M. Yelins’ka ◽  
V.O. Kostenko

The aim of the present study was to investigate the co-effect produced by water-soluble form of quercetin and epigallocatechin-3-gallate (EGCG) on biochemical markers of periodontal organic matrix depolimerization under systemic administration and local application of S. typhi lipopolisaccharide (LPS). The studies were conducted on 30 white rats of the Wistar line weighing 180-220 g, divided into 5 groups: the 1st included intact animals, the 2nd was made up of animals after the combined systemic and local LPS administration, the 3rd and 4th groups included animals, which were being given injections with water-soluble form of quercetin (10 mg / kg) and EGCG (21.1 mg / kg) respectively 3 times a week, starting on the 30th day of the systemic LPS administration, and the 5th group involved rats, which were injected with co-administered water-soluble form of quercetin and EGCG. It has been found out that the co-effect produced by quercetin and EGCG under systemic and local LPS administration is accompanied with reduced concentration of N-acetylneuraminic acid (NANA) by 31.8 and 32.8% respectively in the soft periodontal tissues compared with values for the animals received separate quercetin and EGCG during the experiment. However, no differences have been detected between the groups exposed to combined or separate action of the above mentioned agents in the experiment when assessing free hydroxyproline (FHP) and glycosaminoglycans (GAGs) content in the soft tissues of periodontium. At the same time combined use of quercetin and EGCG under experimental conditions led to the decrease in the FHP content in the alveolar bone by 24.5 and 20.2% respectively compared with values for the animals received separate quercetin and EGCG. NANA concentration was reduced by 35.0 and 41.3% respectively. Thus, the co-administration of water-soluble form of quercetin and epigallocatechin-3-gallate under systemic and local introducing of S. typhi lipopolysaccharide has been proven to be more effective means for preventing and correcting periodontal connective tissue disruption than this occurs at separate administration of each of the polyphenols.

Author(s):  
A.M. Yelins’ka ◽  
V.O. Kostenko

The experiment on 30 white rats was designed to investigate the effect of a water-soluble form of quercetin on collagenolysis and depolymerization of proteoglycans and glycoproteins in both soft and bone tissues of periodontium under the conditions of systemic administration of S. typhi lipopolysaccharide. The animals were divided into 3 groups: the 1st group included intact animals, the 2nd group involved the animals exposed to the systemic administration of S. typhi lipopolysaccharide (pyrogenal), the 3rd group was made up the rats, which were given a water-soluble complex of quercetin and polyvinylpyrrolidone (corvitin) intraperitoneally in a dose of 500 mg / kg (10 mg / kg in terms of quercetin) every 3 days, starting from the 30th day of the experiment. The latter was administered in a dose of 0.4 μg/kg 3 times during the 1st week and once a week for the next 7 weeks. Collagenolysis was assessed by the concentration of free hydroxyproline; the level of depolymerisation of proteoglycans and glycoproteins was assessed by the content of glycosaminoglycans (GAGs) and N-acetylneuraminic acid (NANA) respectively. The introduction of quercetin in the experimental conditions significantly reduced the concentration of free hydroxyproline in soft and bone periodontal tissues by 27.3 and 26.7%, GAG – by 36.3 and 39.9%, and NANA – by 17.6 and 46.8%, respectively compared to the values of the 2nd group. The coefficient of root exposure in molars was inferior to the findings in the group with the modelled systemic inflammatory response by 26.9%. It can be concluded that the use of quercetin in the systemic lipopolysaccharide administration significantly reduces the depolymerisation of the components of the organic matrix in soft and bone periodontal tissues (collagen, proteoglycans and sialoglycoproteins), and limits the resorption of the alveolar process in jaws.


Author(s):  
A.M. Yelins’ka ◽  
V.O. Kostenko

The aim of the present study was to investigate the co-effect produced by water-soluble form of quercetin and SR 11302, an inhibitor of AP-1 transcription factor, on biochemical depolymerization markers of periodontal organic matrix during systemic and local administration of S. typhi lipopolisaccharide (LPS). The studies were conducted on 25 white rats of the Wistar line weighing 180-220 g, divided into 5 groups: the 1st group included the intact animals, the 2nd group was made up of the animals subject to the combined systemic and local LPS administration, the 3rd and 4th groups included animals, which were given injections with water-soluble form of quercetin (10 mg / kg) and AP-1 activation inhibitor SR 11302 (1 mg / kg) respectively 3 times a week starting on the 30th day of the systemic LPS administration, and the 5th group involved rats, which were injected with co-administered water-soluble form of quercetin and SR 11302. It has been found out the the quercetin and SR 11302 co-administration during systemic and local LPS administration is accompanied with reduced concentration of free hydroxyproline and N-acetylneuraminic acid (NANA) in the soft and bone tissues of the periodontium compared with the results obtained during the separate administration of these agents. The content of glycosaminoglycans did not change. We can suggest that the co-administration of the water-soluble form of quercetin and SR 11302, the AP-1 activation inhibitor, during systemic and local administration of the S. typhi lipopolysaccharide is a more effective means of correcting disorders of the periodontal connective tissue than when the agents are used separately.


2020 ◽  
Vol 73 (10) ◽  
pp. 2127-2132
Author(s):  
Ivan V. Yavtushenko ◽  
Svitlana M. Nazarenko ◽  
Oleksandr V. Katrushov ◽  
Vitalii O. Kostenko

The aim: To investigate the effect of water-soluble form of quercetin on the indices reflecting the progression of oxidative-nitrosative stress in the cerebral tissues and the periodontium of rats after experimental TBI. Materials and methods: The studies were conducted on 30 white rats of the Wistar line weighing 180-220 g, divided into 3 groups: the 1st group included pseudo-injured animals (subjected to ether anaesthesia, fixation without TBI modeling), the 2nd group included the animals exposed to modeled moderate TBI, the 3rd group involved the rats, which were given injections with water-soluble form of quercetin (corvitin, “Borshchahivskiy CPP”, Ukraine) intraperitoneally in a daily dose of 10 mg/kg recalculated for quercetin for 7 days following the TBI modeling. The formation of superoxide radical anion (.О2 -), activity of NO-synthase – total (NOS), its constitutive and inducible isoforms (cNOS, iNOS) – and concentration of peroxynitrite were evaluated spectrophotometrically. The level of lipid peroxidation (LPO) in the tissues was evaluated by the formationof a stained trimethine complex during the reaction of tiobarbituric acid (TBA). The activity of the antioxidant system was assessed by increasing in the concentration of TBA active products during 1.5 hour incubation in iron-ascorbate buffer solution, as well as by the activity of antioxidant enzymes – superoxide dismutase (SOD) and catalase. Results: The use of quercetin under the experimental conditions significantly reduced the О2 - generation by NADPH- and NADH-dependent electron transport chains by 30.2 and 35.0% (in the cerebral hemispheres) and by 23.5 and 32.5% (in the soft periodontal tissues), respectively, compared to the findings in the 2nd group. The production of this radical by leukocyte NADPH oxidase in these organs was inferior to the value of the 2nd group by 39.3 and 29.9%. We revealed that the use of quercetin in the experimental conditions probably reduced the activity of NOS, including iNOS, by 38.2 and 45.3% (in the cerebral hemispheres) and by 53.5 and 66.9% (in the soft periodontal tissues), respectively, compared with the findings in the 2nd group. Under these conditions, the cNOS activity went up by 50.0% and doubled, the peroxynitrite content was lower by 19.5 and 32.1% than that in the 2nd group. The administration of quercetin in the experimental conditions significantly reduced the concentration of TBA-active products in the homogenate of cerebral hemispheres and soft periodontal tissues. The development of decompensated LPO is also confirmed by a decrease in the activity of SOD and catalase. Conclusions: on the 7th day after modeling moderate TBI in rats the signs of oxidative-nitrosative stress are found not only in locus morbi (in the tissue of the cerebral hemisphere), but also in distant organs (periodontal tissues). Applying of water-soluble form of quercetin significantly reduces signs of oxidative-nitrosative stress in the tissue of the cerebral hemisphere of rats, as well as in periodontal tissues on the 7th day after moderate TBI modeling.


Author(s):  
A.M. Yelins’ka ◽  
I.I. Starchenko ◽  
V.O. Kostenko

The experiment carried out on 30 white rats was aimed at studying pathomorphological changes in periodontal tissues during lipopolysaccharide-induced systemic inflammatory response and their nature when a water-soluble form of quercetin and epigallocatechin-3-gallate was administered to the animals. The rats were divided into 4 groups: the 1st group included animals after systemic administration of S. typhi lipopolysaccharide (pyrogenal); the 2nd and 3rd group involved animals, which were injected with a water-soluble form of quercetin (10 mg/kg) and epigallocatechin-3-gallate (21.1 mg/kg) intraperitoneally (every 3 days) starting from the 30th day of the experiment. Pyrogenal was administered in a dose of 0.4 μg/kg 3 times during the 1st week and once a week for the next 7 weeks. Sections of 4–6 μm thick were cut from paraffin blocks and stained with hematoxylin and eosin. It has been found out that experimental modeling of a systemic inflammatory response leads to the development of morphological signs of periodontitis, which are manifested by inflammation and destruction of periodontal pockets, the formation of pathological periodontal pockets, destructive changes in bone tissues of the alveolar process and in the cementum of the dental root. The use of the water-soluble form of quercetin and epigallocatechin-3-gallate in the experimental conditions changes the morphological picture of inflammatory and destructive processes in the periodontium: it prevents the formation of purulent exudate, reduces the intensity of the resorption of cementum and bone tissue of the alveolar process, accelerates the development and maturation of granulation tissue in the walls of periodontium, promotes the replacement of bone defects with connective tissue, and enhances the regeneration of cementum.


2019 ◽  
Vol 72 (8) ◽  
pp. 1499-1503
Author(s):  
Alina M. Yelins’ka ◽  
Lilia I. Liashenko ◽  
Vitalii O. Kostenko

Introduction: There has been demonstrated that pharmaceutical effect of epigallocatechin-3-gallate (EGCG), a polyphenol, which is found in green tea (Camellia sinensis), is implemented through the activation of Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2).The importance of Keap1 / Nrf2 / antioxidant response element (ARE) system is determined by the fact that the state of NF-κB- and АР-1-associated pathways depends on its activity. Recent studies have demonstrated the property of quercetin to suppress ubiquitin-dependent proteolysis of complex of NF-κB and its inhibitory protein IκB. All this provides preconditions to eliminate the potentiality of NF-κB-dependent expression of the number of genes of pro-oxidant and pro-inflammatory proteins. However, co-effect produced by quercetin and EGCG on the oxidative nitrosative stress markers in the periodontal tissues is still unclear. The aim: To investigate the co-effect produced by quercetin and an inducer of the Keap1 / Nrf2 / ARE epigallocatechin-3-gallate on markers of oxidative-nitrosative stress in rats’ periodontium under the systemic and local administration of Salmonella typhi lipopolysaccharide (LPS). Materials and methods: The studies were conducted on 30 white rats of the Wistar line, divided into 5 groups: the 1st included intact animals, the 2nd was made up of animals after their exposure to combined systemic and local LPS administration, the 3rd and 4th groups included animals, which were given injections with water-soluble form of quercetin (corvitin) and EGCG respectively, and the 5th group involved rats, which were injected with co-administered corvitin and EGCG. The formation of superoxide anion radical (.О-2 ) was evaluated by a test with nitro blue tetrazolium using spectrophotometry of the periodontal soft tissue homogenate. The total activity of NO-synthase and concentration of peroxynitrite in the homogenate of the soft components of periodontium were evaluated spectrophotometrically. Results: Co-effect produced by corvitin and EGCG under systemic and local LPS administration is accompanied with reduced О-2 production by NADPH-dependent electron transport chains (microsomal and NOS) by 20.0 % (p<0.05) compared with values for the animals received separate corvitin during the experiment. .О-2 generation by the mitochondrial respiratory chain yielded to comparable data of the 3rd and 4th groups by 27.6 % (p<0.01) and 23.8 % (p<0.05) respectively. No differences were found between the groups exposed to combined or separate action of the above mentioned agents in the experiment when assessing О-2 generation by leukocyte NADPH-oxidase. Combined effect of corvitin and EGCG during systemic and local LSP administration showed the decrease in NOS activity and peroxynitrite concentration in periodontal tissues by 53.3 % (p<0.001) and 27.0 % (p<0.02) compared with the findings in the 3rd group, and by 42.0 % (p<0.01) and 22.3 % (p<0.01) in the 4th group. Conclusions: the co-administration of water-soluble form of quercetin and epigallocatechin-3-gallate under systemic and local introducing of lipopolysaccharide Salmonella typhi has been proven to be more effective means for preventing and correcting oxidative-nitrosative stress in the periodontal tissues than this occurs at separate administration of each of the polyphenols.


Author(s):  
A.M. Yelins’ka ◽  
S.M. Nazarenko ◽  
V.O. Kostenko

The study was carried out to investigate the effect produced by water-soluble form of quercetin (corvitin) on the indices of the development of oxidative-nitrosative stress in periodontal soft tissues of rats subjected to systemic inflammatory response. This condition was simulated by using two models: one was induced by the Salmonella typhi lipopolysaccharide (LPS) administration (in a dose of 0.4 μg / kg of body wt three times through the 1st week and once a week for the next 7 weeks), as well as on the 14th day after a moderate craniocerebral injury (CCI). Applying corvitin in a dose of 500 μg / kg (10 μg / kg recalculated as quercetin) every third day starting from the 30th day of the experiment with the use of pyrogenalum reduced the production of superoxide anion radical (.О) by NADPH-dependent electron transport chains (endoplasmic reticulum and NO-synthase) by 18.1%, but did not considerably affect the mitochondrial chain. .О production by leukocyte NADPH-oxidase was by 16.7% lower. The total NO synthase (NOS) activity in periodontal tissues decreased by 40.6%, and the content of peroxynitrite ions was inferior to the relevant result of the group received pyrogenalum by 13.9%. Administration of corvitin in a dose of 500 mg/kg for 7 days after CCI modeling reduced the (.О) production by NADPH-dependent chains by 20.9%, and by mitochondria by 31.7% on the 14th day of post-traumatic period. .О production by leukocyte NADPH-oxidase was by 35.8% lower. NOS activity in periodontal tissues decreased by 45.8%, the content of peroxynitrite ions was inferior to the relevant value in the group with modeled CCI by 25.7%. This suggests the conclusion that applying water-soluble form of quercetin in conditions of systemic inflammatory response limits the signs of oxidative-nitrosative stress in periodontal soft tissues of rats.


Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 537 ◽  
Author(s):  
Jin Liu ◽  
Jianping Ruan ◽  
Michael D. Weir ◽  
Ke Ren ◽  
Abraham Schneider ◽  
...  

Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mandana Sattari ◽  
Ramezan Ali Taheri ◽  
Reza ArefNezhad ◽  
Hossein Motedayyen

Abstract Objective MicroRNA-146a (miR-146a) is a regulator of inflammatory response. Periodontitis is a disease with immune pathophysiology of the periodontium in which the inflammation results in the destruction of the soft tissues and alveolar bone. Therefore, the aim of this study was to investigate the expressions of miR-146a, OPG, and RANKL in diseased and healthy periodontal tissues to understand whether miR-146a expression level may associate with OPG and RANKL mRNA levels and OPG/RANKL ratio after non-surgical periodontal treatment. Methods The levels of miR-146a, RANKL, and OPG in gingival tissues from patients with generalized periodontitis stages II and III and grades A and B (n = 15, group A), patients with generalized periodontitis stages III and IV and grade C (n = 15, group B), and healthy individuals (n = 10) were determined by real-time PCR. The associations of miR-146a expression with OPG and RANKL levels were evaluated. Results The levels of miR-146a in two subgroups within periodontitis patients were significantly higher than healthy subjects (P < 0.0001). MiR-146a showed the increased level in group A of patients compared with group B (P < 0.05). Clinical parameters such as probing depth (PD) and clinical attachment loss (CAL) were significantly higher in patients than control group (P < 0.05). The levels of OPG and RANKL were increased in patients compared with healthy subjects, although the elevated levels were not statistically significant. MiR-146a was not associated with OPG and RANKL levels and OPG/RANKL ratio. Conclusions The results of this study failed to show the associations of miR-146a level with OPG and RANKL levels and OPG/RANKL ratio in periodontitis after non-surgical periodontal treatment.


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Carolyn G. J. Moonen ◽  
Teun J. de Vries ◽  
Patrick Rijkschroeff ◽  
Patrice E. Poubelle ◽  
Elena A. Nicu ◽  
...  

The ligand of the receptor activator of NF-κB (RANKL) is a key molecule in the formation of osteoclasts, the key cells that cause the disease-associated alveolar bone resorption in periodontitis. We hypothesized that polymorphonuclear leukocytes (PMNs), found as the most prominent cells of inflamed periodontal tissues, could play an important role in providing signals to trigger osteoclastogenesis and thus activating pathological bone resorption in periodontitis. RANKL expression was investigated on circulatory PMNs (cPMNs) and oral PMNs (oPMNs) taken from both controls and periodontitis patients. On average, 2.3% and 2.4% RANKL expression was detected on the cPMNs and oPMNs from periodontitis patients, which did not differ significantly from healthy controls. Since cPMNs may acquire a more osteoclastogenesis-facilitating phenotype while migrating into the inflamed periodontium, we next investigated whether stimulated (with LPS, TNF-α, or IL-6) cPMNs have the capacity to contribute to osteoclastogenesis. Enduring surface expression of RANKL for short-lived cells as cPMNs was achieved by fixating stimulated cPMNs. RANKL expression on stimulated cPMNs, as assessed by flow cytometry and immunohistochemistry, was limited (6.48±0.72%,mean expression±SEM) after 24 and 48 hours of stimulation with LPS. Likewise, stimulation with TNF-αand IL-6 resulted in limited RANKL expression levels. These limited levels of expression did not induce osteoclastogenesis when cocultured with preosteoclasts for 10 days. We report that, under the aforementioned experimental conditions, neither cPMNs nor oPMNs directly induced osteoclastogenesis. Further elucidation of the key cellular players and immune mediators that stimulate alveolar bone resorption in periodontitis will help to unravel its pathogenesis.


Author(s):  
Fik V. B.

The aim of this study was to examine the morphometric parameters of the thickness of the epithelial plate of the gingival mucosa, the height of the connective tissue papillae and the diameter of the lumen of hemomicrovascular white rats in the dynamics after eight, ten and twelve weeks of chronic opioid exposure. Experimental studies were performed on white male rats of reproductive age. For twelve weeks, rats were injected intramuscularly with the opioid analgesic nalbuphine at increasing average therapeutic doses of 0.212 to 0.3 mg/kg body weight. Fragments of rat jaws were used for histological and morphometric studies. Based on the analysis of the obtained morphometric parameters of the studied components of the gums, it was found that in the late stages of chronic opioid exposure there was a significant decrease in epithelial thickness and connective tissue papillae and a significant increase in the lumen diameter of hemomicrocirculatory progression of inflammatory-dystrophic changes in periodontal tissues.


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