Rat Model Of Ligature-induced Periodontitis Research Articles

Antimicrobial and anti-inflammatory effects of BenTooth: A natural product blend of burdock root, persimmon leaf extracts, and quercetin on periodontal disease

Periodontal disease represents a condition that exhibits substantial global morbidity, and is characterized by the infection and inflammation of the periodontal tissue effectuated by bacterial pathogens. The present study aimed at evaluating the therapeutic efficacy of BenTooth, an edible natural product mixture comprising burdock root extract, persimmon leaf extract and quercetin, against periodontitis both in vitro and in vivo. BenTooth was examined for antimicrobial properties and its impact on cellular responses related to inflammation and bone resorption. Its effects were also assessed in a rat model of ligature-induced periodontitis. BenTooth demonstrated potent antimicrobial activity against P. gingivalis and S. mutans. In RAW264.7 cells, it notably diminished the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as reduced interleukin-6 and tumor necrosis factor-α levels triggered by P. gingivalis-derived lipopolysaccharide. Furthermore, BenTooth inhibited osteoclastogenesis mediated by the receptor activator of nuclear factor κB ligand. In the rat model, BenTooth consumption mitigated the ligature-induced expansion in distance between the cementoenamel junction and the alveolar bone crest and bolstered the bone volume fraction. These results present BenTooth as a potential therapeutic candidate for the prevention and remediation of periodontal diseases.

Anti-Periodontitis Effects of Dendropanax morbiferus H.Lév Leaf Extract on Ligature-Induced Periodontitis in Rats.

Periodontitis is caused by pathogens in the oral cavity. It is a chronic infectious disease that causes symptoms including gingival bleeding and tooth loss resulting from the destruction of periodontal tissues coupled with inflammation. Dendropanax morbiferus H.Lév (DM) is a natural product that exhibits various biological activities with few side effects. In this study, the potential of DM leaf hot-water extracts (DMWE) as a treatment for periodontitis was determined and its anti-oxidant and anti-inflammatory effects were evaluated. Compounds in DMWE were identified by high-performance liquid chromatography (HPLC) and nitric oxide (NO) and prostaglandin E2 (PGE2) production was measured in RAW 264.7 cells. We measured the gingival index and gingival sulcus depth, and micro-CT was performed in vivo using a ligature-induced periodontitis rat model, which is similar to human periodontitis. The DMWE-treated group exhibited a decrease in cytokine concentration and relieved the gingival index and gingival sulcus depth compared with the periodontitis-induced control group. In addition, micro-CT and histological analysis revealed that DMWE exhibited anti-inflammatory effects and improved alveolar bone loss in periodontitis-induced rats. These findings suggest that DMWE has excellent anti-oxidant and anti-inflammatory effects that protect and prevent periodontal tissue damage and tooth loss caused by the inflammatory response.

The Treatment Efficiency and Microbiota Analysis of Sapindus mukorossi Seed Oil on the Ligature-Induced Periodontitis Rat Model.

Periodontitis is a common oral disease mainly caused by bacterial infection and inflammation of the gingiva. In the prevention or treatment of periodontitis, anti-bacterial agents are used to inhibit pathogen growth, despite increasing levels of bacterial resistance. Sapindus mukorossi Gaertn (SM) seed oil has proven anti-bacterial and anti-inflammation properties. However, the possibility of using this plant to prevent or treat periodontitis has not been reported previously. The aim of this study was to evaluate the effects of SM oil on experimental periodontitis in rats by using micro-CT and microbiota analysis. The distance between cementoenamel junction (CEJ) and alveolar bone crest (ABC) on the sagittal micro-CT slide showed that total bone loss (TBL) was significantly lower in CEJ-ABC distances between SM oil and SM oil-free groups on Day 14. Histology data also showed less alveolar bone resorption, a result consistent result with micro-CT imaging. The microbiota analyzed at phylum and class levels were compared between the SM oil and SM oil-free groups on Day 7 and Day 14. At the phylum level, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria were the dominant bacterium. Firmicutes in box plot analysis was significantly less in the SM oil group than in the SM oil-free group on Day 7. At the class level, Bacteroidia, Gammaproteobacteria, Bacilli, Clostridia, and Erysipelotrichia were the dominant bacteria. The bacteria composition proportion of Bacilli, Clostridiay, and Erysipelotrichia could be seen in the SM oil group significantly less than in t SM oil-free group on Day 7. Overall, the present results show that topical application of SM oil can reduce bone resorption and change bacteria composition in the ligature-induced periodontitis model. According to these results, it is reasonable to suggest SM oil as a potential material for preventing oral disease.

Effects of Lactobacillus curvatus MG5246 on inflammatory markers in Porphyromonas gingivalis lipopolysaccharide-sensitized human gingival fibroblasts and periodontitis rat model.

This study investigated the effects of Lactobacillus curvatus MG5246 on periodontitis inflammation. Cell-free supernatants (CFS) prepared from L. curvatus MG5246 decreased prostaglandin E2 production and cyclooxygenase-2 gene expression by 60% and 78% in Porphyromonas gingivalis-lipopolysaccharide stimulated human gingival fibroblasts at 400μg/mL. Gene expressions of tumor necrosis factor-α, interleukin-6, matrix metalloproteinases, and chemokines were significantly downregulated by CFS treatment (p < 0.05). L. curvatus MG5246 (2 × 108CFU/day, 8weeks) administration significantly improved alveolar bone loss in the ligature-induced periodontitis rat model. Elevated mRNA expression of the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio in the gingival tissue was significantly decreased by L. curvatus MG5246 administration (p < 0.05). Moreover, L. curvatus MG5246 showed sufficient tolerance in simulated gastrointestinal conditions (gastric tolerance: 89.48%, intestinal tolerance: 98.62%) and did not show antibiotic resistance and hemolytic activity. Therefore, L. curvatus MG5246 has the potential as novel oral probiotics.

Thermoresponsive Hydrogel-Based Local Delivery of Simvastatin for the Treatment of Periodontitis.

Except for routine scaling and root planing, there are few effective nonsurgical therapeutic interventions for periodontitis and associated alveolar bone loss. Simvastatin (SIM), one of the 3-hydroxy-3-methylglutaryl-cosenzyme A reductase inhibitors, which is known for its capacity as a lipid-lowering medication, has been proven to be an effective anti-inflammatory and bone anabolic agent that has shown promising benefits in mitigating periodontal bone loss. The local delivery of SIM into the periodontal pocket, however, has been challenging due to SIM's poor water solubility and its lack of osteotropicity. To overcome these issues, we report a novel SIM formulation of a thermoresponsive, osteotropic, injectable hydrogel (PF127) based on pyrophosphorolated pluronic F127 (F127-PPi). After mixing F127-PPi with F127 at a 1:1 ratio, the resulting PF127 was used to dissolve free SIM to generate the SIM-loaded formulation. The thermoresponsive hydrogel's rheologic behavior, erosion and SIM release kinetics, osteotropic property, and biocompatibility were evaluated in vitro. The therapeutic efficacy of SIM-loaded PF127 hydrogel on periodontal bone preservation and inflammation resolution was validated in a ligature-induced periodontitis rat model. Given that SIM is already an approved medication for hyperlipidemia, the data presented here support the translational potential of the SIM-loaded PF127 hydrogel for better clinical management of periodontitis and associated pathologies.

Effect of photobiomodulation therapy as an adjunct to scaling and root planing in a rat model of ligature-induced periodontitis: a histological and radiographic study.

This study aimed to histologically and radiographically evaluate the effectiveness of low-intensity laser irradiation of different wavelengths (660 or 808nm) as an adjunct to scaling and root planing in the treatment of experimental periodontitis in rats. Periodontitis was induced by placing a ligature around the mandibular first molar of the rats. In total, 40 Wistar rats were randomly divided into five groups (n = 8 each): control (CG), periodontal disease (PD), scaling and root planing (SRP), SRP + 660nm laser (GL660) and SRP + 808nm laser (GL808). Groups with laser use received radiation at 6 points in the first molar. The animals were euthanized at baseline and at 7 and 14days after the interventions. Mandibles were surgically removed for histomorphometric and radiographic assessment of periodontal tissues. The GL660 group showed lesser bone loss than the PD group (P < 0.05) and greater alveolar bone margin after 14days, indicating a better long-term treatment response (P < 0.05). These findings suggest that SRP with the 660nm laser as an adjunct results in more favorable radiographic and histological responses than the 808nm laser.

Grape Seed Extract Reduces the Degree of Atherosclerosis in Ligature-Induced Periodontitis in Rats - An Experimental Study.

The associations between periodontitis and cardiovascular diseases have been intensely studied in recent years. Oxidative stress is involved in the initiation and both progression of periodontitis and atherosclerosis. Antioxidants can reduce the effects of oxidative stress on inflammatory diseases. Our aim was to measure the effects of a grape seed extract (GSE), rich in antioxidants, on atherosclerosis caused by ligature-induced periodontitis in rats. Thirty male Wistar rats were randomly divided into three groups of 10: control group, periodontitis group, and periodontitis group treated with GSE (GSE group). Periodontitis was induced by placing an orthodontic wire around the cervix of the first mandibular molar and keeping it in place for 4 weeks. On days 1, 7 and 28, blood samples were taken to assess oxidative stress and inflammation markers (malondialdehyde and glutathione - MDA, reduced glutathione - GSH, C reactive protein) and lipids. After 4 weeks, the animals were euthanized, and aortas were collected for histopathologic examination. MDA was significantly higher in Periodontitis group compared to the other groups only at day 7. GSH was significantly increased in the Control and GSE groups on days 1 and 7, compared to Periodontitis group and on day 28 higher in GSE vs. Periodontitis groups. C reactive protein was significantly increased in the Periodontitis group on days 1 and 7 compared to both groups. Cholesterol was significantly decreased in the aortas of GSE group at day 28 compared to the Periodontitis group. Oral administration of a grape seed extract reduces the oxidative stress, inflammation and atherosclerosis in a rat model of ligature-induced periodontitis.

Alveolar Bone Protective Effect of Hiziki Extracts on the Progression of Periodontitis.

The purpose of this study was to evaluate the effects of hiziki extract on alveolar bone loss, inflammation, and osteo-biomarker expression in hPDL cells (10, 50, 100μg/ml final concentrations in culture medium) and on a ligature-induced periodontitis rat model (50, 100, 200mg/kg with oral administration). Hiziki extract increased alkaline phosphatase activity and mineralized nodule formation in hPDL cell. In western blot analysis, hiziki extract resulted in increased expression of osteoblast markers, including transforming growth factor beta (TGF-β), SMAD anchor for receptor activation (SARA) and runt-related transcription factor 2 (RUNX2) in hDPL cells. Additionally, expression of osteoclast markers and inflammatory cytokines was inhibited, which were receptor activator of NF-κB (RANK), RANK receptor (RANKL) and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). Hiziki extract also prevented alveolar bone loss in a ligature-induced periodontitis rat model through reducing the distance between cementoenamel junction and alveolar bone crest (CBJ-ABC) and furcation involvement. These findings suggested that hiziki extract has prophylactic potential for the prevention of periodontitis through anti-inflammation and, anti-bone resorption effects and the inhibition of alveolar bone destruction.

Simvastatin modulates gingival cytokine and MMP production in a rat model of ligature-induced periodontitis.

PurposeThe aim of this study was to evaluate the effect of simvastatin on the synthesis of cytokines TNF-α and IL-10 and metalloproteinase (MMPs) 2 and 9 in a rat model of ligature-induced periodontitis.Materials and methodsTwenty Wistar rats were used, and a cotton ligature was place in a subgingival position encircling the entire cervix of the first molar of the left (ipsilateral) side of the mandible. The right (contralateral) side of the mandible had no ligature placed and was used as control. After the ligature placement, animals were randomly assigned to two experimental groups (n=10): 1) rats with ligature + vehicle (saline; 10 mL/kg; orally) and 2) rats with ligature + simvastatin (25 mg/kg; orally). After 14 days of treatment, the animals were euthanized by anesthetic overdose and the gingival tissue was removed and homogenized in appropriate buffer. MMP-2 and -9 release as well as the IL-10 and TNF-α levels were detected by enzyme-linked immunosorbent assay. Statistical comparison was performed by unpaired Student’s t-test, with p<0.05 representing significance.ResultsNo differences were observed for TNF-α production between the groups (p>0.05). However, IL-10 was upregulated in simvastatin-treated animals (1.8-fold increase) in comparison with the vehicle-treated group (p<0.05). Simvastatin reduced the gingival levels of MMP-9 (64.3%) in comparison with vehicle-treated samples (p<0.05).ConclusionOral treatment with simvastatin increased the release of IL-10 and reduced the MMP-9 in ligature-induced periodontitis model in rats.

The Proteasome Inhibitor Bortezomib Inhibits Inflammatory Response of Periodontal Ligament Cells and Ameliorates Experimental Periodontitis in Rats.

Periodontitis is a chronic inflammatory disease initiated by bacteria and their virulence factors. Bortezomib (BTZ) is the first proteasome inhibitor for clinical treatment of malignancies. Its anticancer activity is accompanied by an anti-inflammatory effect. However, there are few reports about its anti-inflammatory effect and underlying mechanism in periodontal disease, especially on human periodontal ligament cells (hPDLCs), which are considered a promising cell-based therapy for treating periodontitis. hPDLCs were treated with lipopolysaccharide (LPS) and pretreated with BTZ. mRNA and protein levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β, IL-6, and IL-8 were determined. The anti-inflammatory mechanism of BTZ was studied. Further, experimental rat periodontitis was induced with ligature and LPS injection, and simultaneously and locally treated with BTZ (three injections/week). Four weeks after treatment, microcomputed tomography, immunohistochemical, and histopathologic analyses were performed. Bortezomib administration at safe concentrations (≤1 nM) inhibited production of proinflammatory cytokines in LPS-stimulated hPDLCs via nuclear factor (NF)-kappa B, p38/extracellular signal-regulated kinase, and mitogen-activated protein kinase/activator protein-1 pathways. Moreover, in the LPS and ligature-induced periodontitis rat model, BTZ suppressed expression of TNF-α, IL-1β, IL-6, and IL-8, reduced the ratio of receptor activator of NF-κB ligand/osteoprotegerin, and prevented alveolar bone absorption. These findings demonstrate the anti-inflammatory activity of BTZ against periodontal inflammatory response and present BTZ as a promising therapy for periodontal disease.

Altered gene expression in gingival tissues of the ligature-induced periodontitis rat model

Periodontitis is one of the most common bacterial and infectious diseases characterized by deepening of the periodontal pockets and loss of attachment, and tooth loss. Periodontitis is associated with high levels of various pro-inflammatory mediators, which result in extensive destruction of connective and bone tissues. The aim of this study was to investigate gene expression profiling related periodontitis in gingival tissues of the ligature induced periodontitis rat model. The periodontitis rat model was induced using ligation of the left and right maxillary second molars during 2 weeks. Micro-computed tomography (CT) was performed to identify bone loss of the teeth. To determine the gene expression profile related to periodontitis, up and down regulated gene expression was analyzed using a cDNA microarray (Affymetrix). Differentially expressed gene (DEG) analysis showed that 40 genes were expressed differentially in gingival tissues of the ligature-induced periodontitis rat model compared to those of normal rats (25 up-regulated genes and 15 down-regulated genes). The DAVID system was carried out to identify functional category and signal pathway. It was found that the regulation of these genes be associated with progress of periodontitis in gingival tissues. Microarray data may be helpful for an investigation of the mechanism in the development of periodontitis.

Puerarin decreases bone loss and collagen destruction in rats with ligature-induced periodontitis.

Puerarin, the most abundant isoflavonoid in kudzu root, shows various bioactivities, including bone-sparing, anti-inflammatory and antiproteinase properties. This study aimed to evaluate the effects of puerarin in a rat model of ligature-induced periodontitis. Rat models of periodontitis were developed by bilaterally placing ligatures around the first mandibular molars. Puerarin was administrated daily by gavage at doses of 100, 200 and 400 mg/kg, starting a day before the placement of ligatures. Rats were humanely killed 7 d after the induction of periodontitis. Micro-computed tomography and sirius red staining were used to evaluate alveolar bone loss and collagen destruction, respectively. Histomorphometrical analysis was used to assess the inflammatory cell infiltration. Immunohistochemistry and tartrate-resistant acid phosphatase were used to detect receptor activator of nuclear factor kappa B ligand and osteoprotegerin expressions, and osteoclast activity in the gingiva and alveolar bone. The activation of nuclear factor-kappa B, production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, glycosylation of extracellular matrix metalloproteinase inducer, and production of matrix metalloproteinase (MMP)-2 and MMP-9 in the gingiva were assessed by Western blot. Puerarin at doses of 200 and 400 mg/kg significantly reduced the alveolar bone loss compared with the vehicle group. Collagen destruction and inflammatory cell infiltration were significantly less in the puerarin-treated group (200 mg/kg) compared with that of the vehicle group. Puerarin (200 mg/kg) also reduced the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin and osteoclast activity. Western blot analysis showed that puerarin (200 mg/kg) inhibited the activation of nuclear factor-kappa B p65, which is associated with lower IL-1β and TNF-α production, and reduced the glycosylation of extracellular matrix metalloproteinase inducer, which is associated with lower levels of MMP-2 and MMP-9. Puerarin reduced the alveolar bone loss and collagen destruction in rats with ligature-induced periodontitis by inhibiting the production of RANKL, IL-1β, TNF-α, MMP-2 and MMP-9. Thus, puerarin can be considered a promising agent for adjunctive therapy of periodontitis.

Effect of Cimetidine on Nitro-Oxidative Stress in a Rat Model of Periodontitis.

Background and aimsPeriodontitis is a chronic inflammation that involves nitro-oxidative stress with damaging periodontal structural effects. We aimed to evaluate the consequences of low-dose cimetidine on nitro-oxidative stress in periodontitis.MethodsA rat model of ligature-induced periodontitis was used. After two weeks, the periodontitis groups were treated with cimetidine, aminoguanidine, N-nitro-L-arginine methyl ester and trolox for one week. On day 21, blood was drawn and the serum analyzed for measurement of total nitrites and nitrates, total oxidative status, total antioxidant response, and oxidative stress index.ResultsCimetidine had an inhibitory effect on the synthesis of nitric oxide (p=0.001), total oxidative status (p=0.01) and oxidative stress index (p=0.01). Total antioxidant reactivity was increased by cimetidine (p=0.01). The effects of cimetidine were almost like those of aminoguanidine, NG-nitro-L-arginine methyl ester, and trolox.ConclusionsLow-dose cimetidine can be used as adjunctive host modulatory therapy in chronic periodontitis because it reduces nitro-oxidative stress.

Biomechanical adaptation of the bone-periodontal ligament (PDL)-tooth fibrous joint as a consequence of disease

In this study, an in vivo ligature-induced periodontitis rat model was used to investigate temporal changes to the solid and fluid phases of the joint by correlating shifts in joint biomechanics to adaptive changes in soft and hard tissue morphology and functional space. After 6 and 12 weeks of ligation, coronal regions showed a significant decrease in alveolar crest height, increased expression of TNF-α, and degradation of attachment fibers as indicated by decreased collagen birefringence. Cyclical compression to peak loads of 5–15N at speeds of 0.2–2.0mm/min followed by load relaxation tests showed decreased stiffness and reactionary load rate values, load relaxation, and load recoverability, of ligated joints. Shifts in joint stiffness and reactionary load rate increased with time while shifts in joint relaxation and recoverability decreased between control and ligated groups, complementing measurements of increased tooth displacement as evaluated through digital image correlation. Shifts in functional space between control and ligated joints were significantly increased at the interradicular (Δ10–25μm) and distal coronal (Δ20–45μm) regions. Histology revealed time-dependent increases in nuclei elongation within PDL cells and collagen fiber alignment, uncrimping, and directionality, in 12-week ligated joints compared to random orientation in 6-week ligated joints and to controls. We propose that altered strains from tooth hypermobility could cause varying degrees of solid-to-fluid compaction, alter dampening characteristics of the joint, and potentiate increased adaptation at the risk of joint failure.

The Adaptive Nature of the Bone-Periodontal Ligament-Cementum Complex in a Ligature-Induced Periodontitis Rat Model

The novel aspect of this study involves illustrating significant adaptation of a functionally loaded bone-PDL-cementum complex in a ligature-induced periodontitis rat model. Following 4, 8, and 15 days of ligation, proinflammatory cytokines (TNF-α and RANKL), a mineral resorption indicator (TRAP), and a cell migration and adhesion molecule for tissue regeneration (fibronectin) within the complex were localized and correlated with changes in PDL-space (functional space). At 4 days of ligation, the functional space of the distal complex was widened compared to controls and was positively correlated with an increased expression of TNF-α. At 8 and 15 days, the number of RANKL(+) cells decreased near the mesial alveolar bone crest (ABC) but increased at the distal ABC. TRAP(+) cells on both sides of the complex significantly increased at 8 days. A gradual change in fibronectin expression from the distal PDL-secondary cementum interfaces through precementum layers was observed when compared to increased and abrupt changes at the mesial PDL-cementum and PDL-bone interfaces in ligated and control groups. Based on our results, we hypothesize that compromised strain fields can be created in a diseased periodontium, which in response to prolonged function can significantly alter the original bone and apical cementum formations.

INOS‐Derived Nitric Oxide Stimulates Osteoclast Activity and Alveolar Bone Loss in Ligature‐Induced Periodontitis in Rats

Inflammatory stimuli activate inducible nitric oxide synthase (iNOS) in a variety of cell types, including osteoclasts (OC) and osteoblasts, resulting in sustained NO production. In this study, we evaluate the alveolar bone loss in rats with periodontitis under long-term iNOS inhibition, and the differentiation and activity of OC from iNOS-knockout (KO) mice in vitro. Oral aminoguanidine (an iNOS inhibitor) or water treatment was started 2 weeks before induction of periodontitis. Rats were sacrificed 3, 7, or 14 days after ligature placement, and alveolar bone loss was evaluated. In vitro OC culture experiments were also performed to study the differentiation of freshly isolated bone marrow cells from both iNOS KO and wild-type C57BL/6 mice. OC were counted 6 days later after tartrate-resistant acid phosphatase staining (a marker of osteoclast identity), and bone resorption activity was assessed by counting the number of resorption pits on dentin disks. Rats with ligature showed progressive and significant alveolar bone loss compared to sham animals, and aminoguanidine treatment significantly inhibited ligature-induced bone loss at 7 and 14 days after the induction. In comparison to bone marrow cells from wild-type mice, cells from iNOS KO mice showed decreased OC growth and the resulting OC covered a smaller culture dish area and generated fewer resorption pit counts. Our results demonstrate that iNOS inhibition prevents alveolar bone loss in a rat model of ligature-induced periodontitis, thus confirming that iNOS-derived NO plays a crucial role in the pathogenesis of periodontitis, probably by stimulating OC differentiation and activity.

Effects of verbascoside, biotechnologically purified by Syringa vulgaris plant cell cultures, in a rodent model of periodontitis

Verbascoside has previously been characterized as an effective scavenger of active free radicals and an inhibitor of lipid peroxidation. In the present study, we have investigated the effects of verbascoside from Syringa vulgaris in a rat model of ligature-induced periodontitis. Male Sprague-Dawley rats were lightly anaesthetized with pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed around the cervix of the lower left first molar and knotted medially. Animals received vebascoside 2 mg/kg orally, daily for 8 days. On the eighth day after placement of the ligature, we evaluated several markers of inflammation: (i) myeloperoxidase activity, (ii) thiobarbituric acid-reactant substance measurements, (iii) NF-κB expression, (iv) iNOS expression, (v) the nitration of tyrosine residues, (vi) activation of the nuclear enzyme poly(ADP-ribose) polymerase, (vii) Bax and Bcl-2 expression and (viii) a degree of gingivomucosal tissue injury. Oral administration of verbascoside (2 mg/kg daily for 8 days) significantly decreased all of the parameters of inflammation as described above. These results demonstrate that verbascoside exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage associated with ligature-induced periodontitis.

WY-14643, a Potent Peroxisome Proliferator Activator Receptor-α PPAR-α Agonist Ameliorates the Inflammatory Process Associated to Experimental Periodontitis

We have investigated the effects of WY14643, a potent peroxisome proliferator activator receptor-α (PPAR-α) agonist, in a rat model of ligature-induced periodontitis. Male Sprague-Dawley rats were lightly anaesthetized with pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed around the cervix of the lower left first molar and knotted medially. Animals received WY14643 (1 mg/kg i.p, daily for eight days). Eighths days after placement of the ligature, we evaluated several markers of inflammation such us (1) myeloperoxidase activity, (2) a cytokines and adhesion molecules expression, (3) NF-κB expression, (4) iNOS expression, (5) the nitration of tyrosine residues, (6) activation of the nuclear enzyme poly(ADP-ribose) polymerase, (7) apoptosis, and (8) the degree of gingivomucosal tissues injury. Administration of WY14643 significantly decreased all of the parameters of inflammation as described above. These results demonstrate that WY14643 exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage.

Periodontitis‐induced lipid peroxidation in rat descending aorta is involved in the initiation of atherosclerosis

Periodontitis is a risk factor for the development of atherosclerosis. Recent studies indicate that oxidative mechanisms, including lipid peroxidation, are involved not only in periodontitis but also in atherosclerosis. Lipid peroxidation may play an important role in the pathogenesis of atherosclerosis, particularly during its earliest stages. The purpose of this study was to investigate the relationship between lipid peroxidation induced by periodontitis and the initiation of atherosclerosis. Sixteen rats were randomly divided into two groups of eight rats each. Periodontitis was ligature-induced for 4 wk in the experimental group, whereas the control group was left untreated. After the experimental period, the mandibular first molar regions were resected and then subjected to histological analysis and measurement of hexanoyl-lysine expression as an indicator of lipid peroxidation. Descending aorta was used for measuring the levels of hexanoyl-lysine, reactive oxygen species and lipid deposits, and for real-time polymerase chain reaction microarray analysis. The level of hexanoyl-lysine was also measured in serum. In the experimental group, the levels of hexanoyl-lysine in periodontal tissue and serum increased. Only aorta samples in the experimental group showed lipid accumulation, with increased expression of hexanoyl-lysine, reactive oxygen species and oxidative stress-related genes (including nitric oxide synthases 2 and 3), whereas the superoxide dismutase 1 gene level was down-regulated. In a ligature-induced periodontitis rat model, increased lipid peroxidation was found in serum and aorta as well as in periodontal tissue. Atherosclerosis-related gene expression and histological changes were also stimulated. Periodontitis-induced lipid peroxidation in the aorta may be involved in the early stage of atherosclerosis.

Rosiglitazone Reduces the Evolution of Experimental Periodontitis in the Rat

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) receptor appears to play a pivotal role in the regulation of cellular proliferation and inflammation. Recent evidence also suggests that rosiglitazone, a PPAR-gamma agonist, reduces acute and chronic inflammation. We hypothesized that rosiglitazone would attenuate periodontal inflammation. In the present study, we investigated the effects of rosiglitazone in a rat model of ligature-induced periodontitis. At day 8, ligation significantly induced an increase in neutrophil infiltration, as well as of gingivomucosal tissue expression of iNOS, nitrotyrosine formation, and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitoneal injection of rosiglitazone (10 mg/kg 10% DMSO daily for 8 days) significantly decreased all of the parameters of inflammation, as described above. Analysis of these data demonstrated that rosiglitazone exerted an anti-inflammatory role during experimental periodontitis, and was able to ameliorate the tissue damage associated with ligature-induced periodontitis.