RESUMEN
This study aimed to investigate the impact of minocycline on the alveolar bone in experimental periodontitis in rats. Thirty Wistar rats were randomly assigned to three groups: control without periodontitis; experimental periodontitis induced by ligature; experimental periodontitis + intraperitoneal administration minocycline for seven days. Ligatures remained in place in both periodontitis groups for 14 days. At the end of the experiment, the animals were euthanized and one hemimandible underwent micro-computed tomography (micro-CT) analysis to assess vertical bone loss and alveolar bone quality. Histopathological analysis was performed on the other hemimandible. Statistical analysis was performed using ANOVA with Tukey's post-test (p<0.05). The results showed a significant reduction in vertical bone loss in the animals treated with minocycline compared with untreated animals. Minocycline also preserved the alveolar bone thickness, number, spacing, and bone volume to tissue volume ratio. Histopathological analysis indicated that minocycline reduced bone resorption, decreased inflammatory response, and maintained the bone collagen fibers. This study demonstrated the effectiveness of minocycline in reducing vertical bone loss and preserved bone quality in rats with experimental periodontitis. The results of this study indicate that minocycline has the potential to serve as an additional treatment option for periodontitis. However, further research is warranted to assess the efficacy and safety of minocycline use in patients with periodontitis.
Asunto(s)
Pérdida de Hueso Alveolar , Minociclina , Periodontitis , Ratas Wistar , Microtomografía por Rayos X , Animales , Minociclina/farmacología , Minociclina/uso terapéutico , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/prevención & control , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Ratas , Masculino , Modelos Animales de Enfermedad , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
AIMS: This study aimed to investigate the effects of Umbelliferone (UMB) on the inflammation underlying alveolar bone resorption in mouse periodontitis. METHODS: Male Swiss mice subjected to a ligature of molars were grouped as non-treated (NT), received UMB (15, 45, or 135 mg/kg) or saline daily for 7 days, respectively, and were compared with naïve mice as control. Gingival tissues were evaluated by myeloperoxidase (MPO) activity and interleukin-1ß level by ELISA. The bone resorption was directly assessed on the region between the cement-enamel junction and the alveolar bone crest. Microscopically, histomorphometry of the furcation region, immunofluorescence for nuclear factor-kappa B (NF-ĸB), and immunohistochemistry for tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were performed. Systemically, body mass variation and leukogram were analyzed. RESULTS: Periodontitis significantly increased MPO activity, interleukin-1ß level, and NF-ĸB+ immunofluorescence, and induced severe alveolar bone and furcation resorptions, besides increased TRAP+ and CTSK+ cells compared with naïve. UMB significantly prevented the inflammation by reducing MPO activity, interleukin-1ß level, and NF-ĸB+ intensity, besides reduction of resorption of alveolar bone and furcation area, and TRAP+ and CTSK+ cells compared with the NT group. Periodontitis or UMB treatment did not affect the animals systemically. CONCLUSION: UMB improved periodontitis by reducing inflammation and bone markers.
Asunto(s)
Pérdida de Hueso Alveolar , Interleucina-1beta , Periodontitis , Umbeliferonas , Animales , Masculino , Ratones , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Umbeliferonas/uso terapéutico , Umbeliferonas/farmacología , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , FN-kappa B/metabolismo , Fosfatasa Ácida Tartratorresistente/metabolismo , Peroxidasa , Inflamación , Catepsina K , Ligadura , Encía/patología , Encía/efectos de los fármacosRESUMEN
OBJECTIVE: This study aimed to investigate the effects of systemic administration of P. eurycarpa Yalt. plant extract on alveolar bone loss and oxidative stress biomarkers in gingival tissue in a rat model of experimental periodontitis. METHODOLOGY: 32 male Wistar albino rats, weighing 200-250 g, were divided into four groups (n=8): Healthy control (HC), Experimental periodontitis control (EPC), Experimental periodontitis 400 mg/kg (EP400), Experimental periodontitis 800 mg/kg (EP800). Experimental periodontitis was induced using the ligating method. Distilled water was administered to the HC and EPC groups and the plant extract was administered to the EP400 and EP800 groups by oral gavage at doses of 400 mg/kg and 800 mg/kg, respectively. The rats were sacrificed on the 15th day. The values of glutathione peroxidase GSH-Px, malondialdehyde (MDA), superoxide dismustase (SOD), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in the gingival tissues were analyzed by ELISA tests. Alveolar bone loss was assessed using micro-CT images of the maxilla. RESULTS: Although the IL-1ß, TOS, OSI results of the healthy control group were lower than those of the other groups, the TAS values were higher (p<0.05). No significant difference was found in the biochemical parameters among the EPC, EP400, and EP800 groups (p>0.05). Alveolar bone loss was significantly reduced in the extract groups compared to the EPC group (p<0.001). CONCLUSION: Within the limitations of this study, it was observed that the systemic P. eurycarpa extract application reduced alveolar bone loss in a rat model of experimental periodontitis. Further studies are needed to elucidate the beneficial effects of P. eurycarpa.
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Pérdida de Hueso Alveolar , Periodontitis , Pistacia , Ratas , Animales , Ratas Wistar , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Periodontitis/tratamiento farmacológico , Periodontitis/prevención & control , Estrés Oxidativo , Antioxidantes/farmacología , Antioxidantes/análisis , Oxidantes , Extractos Vegetales/farmacologíaRESUMEN
OBJECTIVE: The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of oxytocin in bone loss and gum inflammatory mediators in a rat model of experimental periodontitis. BACKGROUND DATA: Current evidence supports the hypothesis of a disbalance between the oral microbiota and the host's immune response in the pathogenesis of periodontitis. Increased complexity of the microbial biofilm present in the periodontal pocket leads to local production of nitrogen and oxygen-reactive species, cytokines, chemokines, and other proinflammatory mediators which contribute to periodontal tissue destruction and bone loss. Oxytocin has been suggested to participate in the modulation of immune and inflammatory processes. We have previously shown that oxytocin, nitric oxide, and endocannabinoid system interact providing a mechanism of regulation for systemic inflammation. Here, we aimed at investigating not only the presence and levels of expression of oxytocin receptors on healthy and inflamed gingiva, but also the effects of oxytocin treatment on alveolar bone loss, and systemic and gum expression of inflammatory mediators involved in periodontal tissue damage using ligature-induced periodontitis. Therefore, anti-inflammatory strategies oriented at modulating the host's immune response could be valuable adjuvants to the main treatment of periodontal disease. METHODS: We used an animal model of ligature-induced periodontitis involving the placement of a linen thread (Barbour flax 100% linen suture, No. 50; size 2/0) ligature around the neck of first lower molars of adult male rats. The ligature was left in place during the entire experiment (7 days) until euthanasia. Animals with periodontitis received daily treatment with oxytocin (OXT, 1000 µg/kg, sc.) or vehicle and/or atosiban (3 mg/kg, sc.), an antagonist of oxytocin receptors. The distance between the cement-enamel junction and the alveolar bone crest was measured in stained hemimandibles in the long axis of both buccal and lingual surfaces of both inferior first molars using a caliper. TNF-α levels in plasma were determined using specific rat enzyme-linked immunosorbent assays (ELISA). OXT receptors, IL-6, IL-1ß, and TNF-α expression were determined in gingival tissues by semiquantitative or real-time PCR. RESULTS: We show that oxytocin receptors are expressed in normal and inflamed gingival tissues in male rats. We also show that the systemic administration of oxytocin prevents the experimental periodontitis-induced increased gum expression of oxytocin receptors, TNF-α, IL-6, and IL-1ß (p < .05). Furthermore, we observed a reduction in bone loss in rats treated with oxytocin in our model. CONCLUSIONS: Our results demonstrate that oxytocin is a novel and potent modulator of the gingival inflammatory process together with bone loss preventing effects in an experimental model of ligature-induced periodontitis.
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Pérdida de Hueso Alveolar , Periodontitis , Ratas , Masculino , Animales , Oxitocina/uso terapéutico , Oxitocina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Receptores de Oxitocina/metabolismo , Modelos Animales de Enfermedad , Periodontitis/metabolismo , Encía/metabolismo , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/etiología , Proceso Alveolar/metabolismo , Mediadores de Inflamación/metabolismoRESUMEN
BACKGROUND: Periodontal regeneration faces multiple challenges, the most important being cellular insufficiency. In an attempt to improve defect cellularity, we aimed to demonstrate enhancing cellular attraction using arginine-glycine-aspartic acid (RGD) adhesion molecule legend blended hydrogel within the intrabony defects. METHODOLOGY: Forty-five intrabony defects were selected from patients with stage III or IV - grade A or B periodontitis and divided randomly into three equal groups of 15 each: group1 (G1): received minimally invasive surgical technique (MIST) alone, group2 (G2): received MIST and placebo hydrogel injection, and group3 (G3): were treated with MIST and RGD hydrogel injection. Primary outcomes 6 months following therapy were; defect base fill (DBF) and defect width measurement (DW); secondary outcomes were clinical attachment level (CAL), pocket depth (PD), plaque index (PI), gingival index (GI), and biochemical analysis of bone morphogenetic protein (BMP-2) evaluated at 1,7,14 and 21 days following therapy. RESULTS: Significant improvements in DBF, CAL, and PD were observed in the three studied groups 6 months following therapy compared to baseline (p<0.05). A significant improvement in DBF was reported in G3 compared to G1 and 2 (p=0.005). Additionally, a significantly higher CAL gain was reported in G3 compared to that of G1 (p=0.02). Group 3 was associated with a significantly higher level of BMP-2 compared to G1 and G2 in all reported periods. CONCLUSION: RGD peptide carried on a hydrogel delivery agent and contained with a minimally invasive flap could be a reliable option in improving the outcomes of periodontal therapy.
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Pérdida de Hueso Alveolar , Procedimientos Quirúrgicos Mínimamente Invasivos , Humanos , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/cirugía , Estudios de Seguimiento , Regeneración Tisular Guiada Periodontal/métodos , Hidrogeles , Integrinas , Oligopéptidos , Pérdida de la Inserción Periodontal , Bolsa Periodontal , Resultado del TratamientoRESUMEN
Surgical procedures, radiotherapy, and chemotherapy, individually or in association, are current oncological treatments. Among the most used chemotherapy drugs, 5-fluorouracil (5FU) is an antimetabolite with a broad spectrum of action. This study evaluated the effects of probiotics (PRO) as an adjuvant to the treatment of experimental periodontitis (EP) in rats immunosuppressed with 5FU.108 rats were randomly allocated to six different groups: EP; SS - systemic treatment with saline solution (SS); 5FU - systemic treatment with 5FU; 5FU+PRO - systemic treatment with 5FU, followed by the local administration of Saccharomyces cerevisiae ; 5FU+SRP - systemic treatment with 5-FU, followed by scaling and root planing (SRP); and 5FU+SRP+PRO - systemic treatment with 5FU followed by local treatments with SRP and PRO. Immunosuppression was obtained at two points: at the time of ligature installation and after 48 h. Six animals from each group were euthanized at seven, 15, and 30 d and hemimandibles were collected and processed for histopathological, histometric, and immunohistochemical analysis. Data were subjected to statistical analysis (α=5%). At 7 d, the 5FU+PRO group showed less bone resorption and better structured connective tissue compared with the EP, SS, 5FU+SRP, and 5FU+SRP+PRO groups. At 15 d, the 5FU+SRP group showed a greater intensity of the inflammatory response (p<0.05). At 30 d, the 5FU+SRP+PRO group showed better structured bone tissue and a higher percentage of bone tissue (PBT) than the EP, SS, 5FU, and 5FU+PRO groups (p<0.05). The use of Saccharomyces cerevisiae as monotherapy or as an adjuvant to periodontal therapy may have a positive effect on bone repair in immunosuppressed conditions.
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Pérdida de Hueso Alveolar , Periodontitis , Ratas , Animales , Ratas Wistar , Saccharomyces cerevisiae , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/patología , Periodontitis/patología , Raspado Dental/métodos , Aplanamiento de la Raíz/métodos , Adyuvantes Inmunológicos , Fluorouracilo/farmacología , Fluorouracilo/uso terapéuticoRESUMEN
OBJECTIVE: This systematic review aimed to evaluate the effects of hyaluronic acid (HA) alone or in combination with any bone substitute for the treatment of intrabony defects (IBDs). MATERIAL AND METHODS: Six databases were searched up to April 2022 to find randomized clinical trials comparing the clinical effects of open flap debridement (OFD) + HA versus OFD alone (first group) or OFD + HA + bone substitutes versus OFD + bone substitutes (second group) in the treatment of IBDs with a follow-up of at least 3 months. Random effects models of mean differences were used to determine the clinical attachment level (CAL) gain, probing depth (PD) reduction, and radiographic bone fill (RBF). RESULTS: Of the 276 studies identified, 6 were included in the qualitative synthesis, and 5 in the meta-analyses. The meta-analyses in the first group showed a statistically significant differences for CAL gain (mean difference [MD]:1.00; 95% confidence interval [CI]:0.65 - 1.35; n = 2) and PD reduction (MD: 0.76; 95%CI: 0.34 - 1.17; n = 2) favoring HA + OFD at 6 months. However, in the second group, the meta-analyses did no show additional effect of HA in association with bone substitute was demonstrated for either CAL gain (MD: 0.57; 95%CI: - 0.30 - 1.43; n = 2) or PD reduction (MD: 1.05; 95%CI: - 0.38 - 2.47; n = 2) but did show significant differences for RBF (MD: 0.57; 95%CI: 0.15 - 0.99; n = 2) at 12 months. CONCLUSION: Compared with OFD alone, local application of HA in the treatment of IBDs provided a significant CAL gain and PD reduction at 6 months. However, its combination with bone substitutes showed no statistically significant differences at 12 months. CLINICAL RELEVANCE: The use of OFD + HA improves the CAL and PD in the treatment of IBDs compared to OFD only after 6 months of follow-up. These results are not maintained after 12 months.
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Pérdida de Hueso Alveolar , Sustitutos de Huesos , Humanos , Sustitutos de Huesos/farmacología , Sustitutos de Huesos/uso terapéutico , Ácido Hialurónico/farmacología , Ácido Hialurónico/uso terapéutico , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/cirugía , Resultado del Tratamiento , Desbridamiento , Regeneración Tisular Guiada Periodontal/métodos , Pérdida de la Inserción Periodontal/tratamiento farmacológico , Estudios de SeguimientoRESUMEN
Cinnamaldehyde is a natural product with anti-inflammatory and immune-modulatory properties, known to regulate host responses to bacterial stimuli. This study aimed to investigate the effects of cinnamaldehyde on ligature-induced periodontitis in rats, and its impact on the modulation of human peripheral blood mononuclear cells (PBMC). Male Wistar rats were assigned into three groups:i) control: no ligature + vehicle; ii) ligature: ligature + vehicle; and iii) ligature + cinnamaldehyde (50 mg/kg); all treatments by daily oral gavage. After 14 days of induced periodontitis, the hemimandibles were collected for bone loss evaluation. The gingival levels of IL-1ß, MMP-9 and iNOS mRNA were evaluated. Nitric oxide (NO) was measured in both rat saliva and plasma. PBMC were stimulated with Aggregatibacter actinomycetemcomitans (Aa) in the presence or absence of cinnamaldehyde (5, 20 e 40 µM), and cytokine production was quantified in cell supernatant. Proliferating lymphocytes were taken for flow cytometer reading, while culture supernatants were used for IFN-γ and IL-10 assessment. The ligature group had both increased alveolar bone loss and gingival expression of IL-1ß, MMP-9 and iNOS compared to the control group. All parameters were attenuated by cinnamaldehyde treatment. Lower salivary but not plasma NO was detected in the cinnamaldehyde compared to the ligature group. Aa-stimulated PBMCs treated with cinnamaldehyde produced less IL-1ß; the compound also attenuated lymphocyte proliferation in a dose-dependent manner, as well as cell IL-10 production. Cinnamaldehyde treatment reduced periodontal bone loss, and downregulated key inflammatory mediators and human PBMC responses, pointing to novel potential therapeutic effects of this compound.
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Pérdida de Hueso Alveolar , Periodontitis , Humanos , Ratas , Masculino , Animales , Ratas Wistar , Leucocitos Mononucleares/metabolismo , Interleucina-10/uso terapéutico , Metaloproteinasa 9 de la Matriz , Periodontitis/metabolismo , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/metabolismo , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: In this study, we investigated the modulatory effects of PI3Kγ on IL-17A expression and the progression of experimental periodontitis in vivo. METHODS: Ligature-induced periodontitis was developed around the first molar of mice. Animals were treated with anti-mouse IL-17A or IPI-549 (PI3Kγ inhibitor). In addition, PI3Kγ-deficient mice (PI3Kγ-/-) were used in the study. Alveolar bone loss was measured and real-time PCR of Il17a and Rankl genes was performed. A bioinformatics analysis was carried out using the Gene Set Enrichment Analysis computational tool. RESULTS: Nine days after ligature placement, alveolar bone loss scores were significantly increased, with upregulation of Il17a and Rankl genes in the gingival tissues. Treatment with anti-mouse IL-17A (100 µg/mice) significantly attenuated alveolar bone loss. Mice with ligature-induced periodontitis treated with IPI-549 (3 mg/kg) or PI3Kγ-/- mice showed reduced alveolar bone loss and downregulation of Il17a and Rankl gene expression in the gingival tissues. Consistent with this, the bioinformatics analysis showed upregulation of IL17F, IL17A, IL17D, and STAT3 genes, as well as greater activation of IL-17 and PI3KCI pathways (upregulation of PIK3CG gene) in the gingival tissue of patients with periodontitis. CONCLUSION: PI3Kγ plays an important role in modulating IL-17A expression and alveolar bone loss in vivo and can be considered a promising pathway for the management of periodontal disease and the development of new therapies.
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Pérdida de Hueso Alveolar , Periodontitis , Animales , Ratones , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/genética , Interleucina-17/genética , Interleucina-17/metabolismo , Periodontitis/tratamiento farmacológico , Periodontitis/genética , Encía/metabolismo , Ligadura , Modelos Animales de EnfermedadRESUMEN
Several studies have investigated the effects of natural products in the treatment of diseases. Traditional Amazonian populations commonly use copaiba due to its well-known anti-inflammatory, antibacterial, and healing properties. In this study, we aimed to investigate the effects of systemic administration of copaiba oleoresin (Copaifera reticulata Ducke) on ligature-induced periodontitis in rats. To do so, 21 adult rats were divided into three groups (n = 7 each): a control group, ligature-induced periodontitis group, and ligature-induced periodontitis group treated with copaiba oleoresin (200 mg/kg/day). The ligature remained from day 0 to 14, and the copaiba oleoresin was administered via oral gavage during the last seven days. On day 14, the animals were euthanized, and mandibles were collected for histopathological evaluation and microcomputed tomography analysis. Our data showed that the administration of copaiba considerably reduced the inflammatory profile. Moreover, copaiba oleoresin limited alveolar bone loss, increased trabecular thickness and bone-to-tissue volume ratio, and decreased the number of trabeculae compared with those of the untreated experimental periodontitis group. Our findings provide pioneering evidence that supports the potential of copaiba oleoresin in reducing periodontitis-induced alveolar bone damage in rats.
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Pérdida de Hueso Alveolar , Fabaceae , Periodontitis , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/etiología , Animales , Antibacterianos , Antiinflamatorios , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Resinas de Plantas , Microtomografía por Rayos XRESUMEN
OBJECTIVES: The impact of rheumatoid arthritis (RA) on the shaping of the oral and gut microbiome raises the question of whether and how RA treatment modifies microbial communities. We examined changes in the oral and gut microbiota in a mouse model of antigen-induced arthritis (AIA) treated or not with methotrexate (MTX). METHODS: Maxillae and stools were evaluated by the MiSeq platform of the V4 region of the 16S rRNA gene. Alveolar bone parameters were analysed by micro-computed tomography. Moreover, arthritis-induced changes in hyperalgesia and oedema were assessed, along with the impact on periodontal bone health. RESULTS: Microbial communities in MTX-treated AIA mice revealed distinct clusters compared to the control and AIA groups. Overall, MTX impacted the richness and variability of microorganisms in the oral-gut axis microbiome at the phylum level. Regarding the oral microbiome, while in the control group the most dominant phylum was Firmicutes, in the AIA group there was a shift towards the predominance of Campilobacteriota and Bacteroidetes associated with the disease. MTX treatment led to greater dominance of the health-associated phylum Proteobacteria. In the gut microbiome, AIA induction resulted in increased abundance of the Verrucomicrobiota phylum, and MTX treatment restored its levels compared to control. Importantly, the MTX-treated AIA animals had significantly less periodontal bone loss, as well as decreased hyperalgesia and joint oedema compared to the AIA animals. CONCLUSION: Data suggest the benefit of MTX treatment in protecting alveolar bone, in addition to providing new insights on the drug-microbiome interaction in the course of RA.
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Pérdida de Hueso Alveolar , Artritis Experimental , Artritis Reumatoide , Microbioma Gastrointestinal , Microbiota , Pérdida de Hueso Alveolar/tratamiento farmacológico , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Edema/complicaciones , Hiperalgesia/complicaciones , Metotrexato/farmacología , Metotrexato/uso terapéutico , Ratones , ARN Ribosómico 16S/genética , Microtomografía por Rayos XRESUMEN
OBJECTIVE: Inflammation-related immune responses and bone metabolism lead to extensive tooth loss in periodontitis.. This study aims to investigate the effect of peroxisome proliferator-activated receptor (PPAR) alpha agonist anti-inflammatory treatment in vitro and in ligature-induced experimental periodontitis in vivo . METHODOLOGY: Splenocytes were isolated from C57BL/6J mice and cultured for 48 hours under the following conditions: control, P. gingivalis lipopolysaccharide (LPS) (1 µg/ml); experimental, LPS (1 µg/ml) + PPARα agonist (fenofibrate) at 1, 10, 50, 100 µM. MRNA and secreted protein levels of TNF-α expression were detected by RT-qPCR and ELISA, respectively. Silk ligatures (7-0) were tied around maxillary second molars of C57BL/6J mice for two weeks. Optimized doses of fenofibrate (50 µM) and vehicle control were injected into the contralateral side of the palatal gingiva on days three, six, and nine. At day 14, bone resorption, osteoclastogenesis, and gingival mRNA expression levels of TNF-α, IL-1ß, IL-6, and RANKL/OPG were measured by micro-computed tomography, Tartrate-resistant acid phosphatase (TRAP) staining, and Real-time quantitative PCR, respectively. RESULTS: TNF-α expression in cultured spleen cells were significantly increased in the presence of LPS, when compared with the control group, and significantly reduced by fenofibrate treatment in a dose-dependent manner from 1-100 µM (p<0.05). Gingival mRNA levels of TNF-α, IL-1ß, IL-6, and the ratio of RANKL/OPG, were significantly decreased after injection of fenofibrate, when compared to the control side (p<0.05). Periodontal bone loss and TRAP positive cell formation were significantly decreased on the side with an injection of fenofibrate, as compared to the control side (p<0.05). CONCLUSIONS: An anti-inflammatory treatment, PPARα agonist, inhibited inflammation and periodontal bone loss in ligature-induced experimental periodontitis.
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Pérdida de Hueso Alveolar , Periodontitis , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Animales , Ratones , Ratones Endogámicos C57BL , PPAR alfa/uso terapéutico , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Microtomografía por Rayos XRESUMEN
PURPOSE: The determination on how antineoplastic agents interfere on the progression of periodontitis is critical for improvement and even development of novel therapeutic approaches for periodontal management. This study evaluated the influence of chemotherapy with 5-fluorouracil (5-FU) or cisplatin (CIS) on healthy periodontal tissues and on the progression of experimental periodontitis (EP). METHODS: One hundred forty-four male rats were divided into six groups (n = 24). Each group was treated with physiological saline solution (PSS) 0.9%, 5-FU, or CIS. Experimental periodontitis (EP) was induced by ligature placement. Animals were euthanized at 7, 15, and 30 days after treatment. Data were statistically analyzed (p ≤ 0.05). RESULTS: The groups with EP and treated with 5-FU or CIS showed lower percentage of bone volume in the furcation region and higher percentage of alveolar bone loss, higher number of TRAP-positive cells, and lower number of PCNA-positive cells when compared group with EP and treated with PSS (p ≤ 0.05). Groups with EP and treated with 5-FU or CIS showed high immunolabelling pattern of RANKL, TNF-α, and IL-1ß, moderate of BAX, and low of HIF-1α. Histological analysis showed severe tissue breakdown in the groups with EP and treated with 5-FU or CIS. CONCLUSIONS: Chemotherapy with antineoplastic agents 5-FU and CIS increased the intensity and duration of the inflammation and compromised tissue repair by reduction in cellular and vascular turnover. The more severe periodontal breakdown was caused by 5-FU.
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Pérdida de Hueso Alveolar , Antineoplásicos , Periodontitis , Pérdida de Hueso Alveolar/tratamiento farmacológico , Animales , Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Fluorouracilo/uso terapéutico , Masculino , Periodontitis/tratamiento farmacológico , Ratas , Ratas WistarRESUMEN
BACKGROUND: Previous studies have shown that latex proteins from Plumeria pudica (LPPp) have anti-inflammatory and antioxidant activity. Therefore, the aim of this study was to evaluate the effects in rats of LPPp on ligature-induced periodontitis, an inflammatory disease. METHODS: The animals were divided into groups: saline (animals without induction of periodontitis), periodontitis (induced periodontitis and untreated) and LPPp (induced periodontitis and treated with 40 mg/kg). The following parameters were evaluated after 20 consecutive days of treatment: gingival bleeding index (GBI), probing pocket depth (PPD), alveolar bone height (ABH) and gingival myeloperoxidase (MPO) activity. In the hepatic tissue, malondialdehyde (MDA), glutathione (GSH) and histopathological alterations were evaluated. Blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. RESULTS: Significant reduction in GBI, PPD and gingival MPO activity and ABH was seen in animals treated with LPPp compared with periodontitis. Values of GSH, MDA, ALT and histopathological evaluation were preserved in animals treated with LPPp. CONCLUSIONS: Treatment with LPPp improved clinical aspects of periodontitis, reduced the blood and hepatic alterations and prevented alveolar bone loss. Data suggest that LPPp have potential for treatment of periodontitis.
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Pérdida de Hueso Alveolar , Apocynaceae , Periodontitis , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/prevención & control , Animales , Apocynaceae/metabolismo , Látex/metabolismo , Látex/farmacología , Látex/uso terapéutico , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Ratas , Ratas WistarRESUMEN
Periodontal disease (PD) is a polymicrobial chronic inflammatory condition of the supporting tissues around the teeth, leading to the destruction of surrounding connective tissue. During the progression of PD, osteoclasts play a crucial role in the resorption of alveolar bone that eventually leads to the loss of teeth if the PD is left untreated. Therefore, the development of antiresorptive therapies targeting bone-resorbing cells will significantly benefit the treatment of PD. Here, we demonstrate the inhibitory effect of CsinCPI-2, a novel cysteine peptidase inhibitor from the orange tree, on periodontitis-induced inflammation, alveolar bone loss, and osteoclast differentiation. Using the ligature-induced periodontitis model in mice, we show that treatment with CsinCPI-2 (0.8 µg/g of body weight) significantly reduced inflammatory cell infiltrate in the connective tissue and prevented the loss of alveolar bone mass (BV/TV) caused by PD, effects associated with diminished numbers of TRAP-positive multinucleated cells. Furthermore, CsinCPI-2 significantly downregulated the numbers of inflammatory cells expressing CD3, CD45, MAC387, and IL-1ß. In vitro, CsinCPI-2 inhibited RANKL-induced TRAP+ multinucleated osteoclast formation in mouse bone marrow macrophage cultures in a concentration-dependent manner. This effect was not due to cytotoxicity, as demonstrated by the MTT assay. CsinCPI-2 inhibited RANKL-induced mRNA expression of Acp5, Calcr, and Ctsk, as well as the RANKL-induced upregulation of Nfatc1, a crucial transcription factor for osteoclast differentiation. Based on our findings, CsinCPI-2 prevents bone loss induced by PD by controlling the inflammatory process and acting directly on osteoclastogenesis, suggesting an interesting potential for CsinCPI-2 in the strategy for PD treatment.
Asunto(s)
Pérdida de Hueso Alveolar , Resorción Ósea , Cistatinas/farmacología , Periodontitis , Inhibidores de Proteasas/farmacología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Animales , Diferenciación Celular , Ratones , Osteoclastos , Osteogénesis , Periodontitis/tratamiento farmacológico , Ligando RANKRESUMEN
La periodontitis es una patología inflamatoria que aumenta la resorción de hueso alveolar (HA), pérdida de la inserción dentaria y posible exfoliación. Evaluamos el efecto de la administración intermitente de bajas dosis de parathormona (PTH) 1-34 sobre la recuperación de la masa ósea pérdida en un modelo experimental de periodontitis inducida por una ligadura periodontal (LP) con hilo de algodón alrededor de la pieza dentaria. Las ratas fueron divididas luego de 5 días en instaurada la periodontitis en: CT LP sin trata-miento y PTH LP tratados con 0,2 µg/kg PTH 1-34 subcutánea local, tres veces por semana por 17 días. El control absoluto fue un tercer grupo sin LP (CT). Se estudiaron parámetros antropométricos, bioquímicos e histomosfométricos en tibias y hemimandibulas. La calcemia, fosfatemia, CTX sérico, PTHi y vo-lumen óseo (BV/TV%) de tibias fueron similares en los tres grupos. El BV/TV% del HA fue significativamente menor en PTH LP respecto de CT pero mayor que CT LP (p<0.05). La pérdida ósea de HA porcentual fue significativamente mayor en CT LP (p<0.05). La altura del ligamento periodontal fue significativamente menor en PTH LP que en CT (p<0.05) y mayor respecto de CT LP, sin alcanzar diferencias significativas. Los resultados del presente estudio piloto sugieren que la administración intermitente de PTH en bajas dosis y durante un periodo de tiempo corto disminuye la progresión de la enfermedad periodontal sin generar efectos sistémicos. Como no se logró regenerar totalmente el tejido periodontal se requieren estudios adicionales. (AU)
Periodontitis is an inflammatory chronic disease with high prevalence in adults that induces a progressive alveolar bone (AB) loss leading to tooth loss. Experimental periodontitis can be induced in rats by cotton ligature placement (LP) in the gingival sulcus around the molar teeth. The biofilm accumulation and disruption of the gingival epithelium lead to bone resorption. We investigated whether intermittent administration of a low dose of PTH 1-34 may recover the alveolar bone loss in the experimental periodontitis induced in female Wistar rats. Animals were randomly divided in two groups which were subcutaneously injected with: saline solution (CT LP) or 0,2 µg/kg PTH 1-34 (PTH LP) three times per week during 17 days. Unligated rats were taken as healthy controls (CT). Anthropometric, biochemical and histologic analysis of tibia and hemimandible were done. No differences in serum calcium, phosphorus, CTX, PTHi or subchondral tibia bone volume (BV/TV%) were observed between the three groups. AB BV/TV% was significantly lower in PTH LP than in CT but higher than in CT LP (p<0.05). The highest percentage of AB loss was observed in CT LP. The height of periodontal ligament was lower in PTH LP than in CT (p<0.05) but not significantly higher than CT LP.The increase in AB loss by experimental periodontitis appears to be corrected by the intermittent administration of low doses of PTH without systemic effect. As the recovery of periodontal tissue was only partial, additional studies should be done.
Asunto(s)
Animales , Femenino , Ratas , Periodontitis/tratamiento farmacológico , Pérdida de Hueso Alveolar/tratamiento farmacológico , Teriparatido/administración & dosificación , Tibia/anatomía & histología , Tibia/química , Ratas Wistar , Progresión de la Enfermedad , Modelos Animales , Mandíbula/anatomía & histología , Mandíbula/químicaRESUMEN
Periodontal disease (PD) is a chronic destructive inflammatory disease of the tooth-supporting structures that leads to tooth loss at its advanced stages. Although the disease is initiated by a complex organization of oral microorganisms in the form of a plaque biofilm, it is the uncontrolled immune response to periodontal pathogens that fuels periodontal tissue destruction. IL-17A has been identified as a key cytokine in the pathogenesis of PD. Despite its well documented role in host defense against invading pathogens at oral barrier sites, IL-17A-mediated signaling can also lead to a detrimental inflammatory response, causing periodontal bone destruction. In this study, we developed a local sustained delivery system that restrains IL-17A hyperactivity in periodontal tissues by incorporating neutralizing anti-IL-17A Abs in poly(lactic-coglycolic) acid microparticles (MP). This formulation allowed for controlled release of anti-IL-17A in the periodontium of mice with ligature-induced PD. Local delivery of anti-IL-17A MP after murine PD induction inhibited alveolar bone loss and osteoclastic activity. The anti-IL-17A MP formulation also decreased expression of IL-6, an IL-17A target gene known to induce bone resorption in periodontal tissues. This study demonstrates proof of concept that local and sustained release of IL-17A Abs constitutes a promising therapeutic strategy for PD and may be applicable to other osteolytic bone diseases mediated by IL-17A-driven inflammation.
Asunto(s)
Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/inmunología , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Sistemas de Liberación de Medicamentos/métodos , Interleucina-17/inmunología , Periodontitis/tratamiento farmacológico , Periodontitis/inmunología , Animales , Cápsulas , Modelos Animales de Enfermedad , Composición de Medicamentos/métodos , Liberación de Fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Osteólisis/tratamiento farmacológico , Osteólisis/inmunología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aimed to assess the effect of a novel synthetic chalcone, Chalcone T4, on a murine model of periodontitis and on RANKL-induced osteoclastogenesis in vitro. BACKGROUND: Chalcones are natural compounds with anti-inflammatory properties, and its synthetic analogs with enhanced biological effects have potential as therapeutic agents. Periodontitis is characterized by chronic inflammation of the periodontium and alveolar bone resorption. Safe and effective anti-inflammatory agents can have an important additive effect in the treatment in this disease. METHODS: Periodontitis was induced via the installation of a ligature around the first molar. Rats (n = 32) received Chalcone T4 (5 and 50 mg/kg) or distilled water by gavage daily for 15 days. Outcomes assessed were bone resorption (µCT), TNF-α production (ELISA), cellular infiltrate, and collagen content (stereometric analysis, CD45+ cells by immunohistochemistry), and activation of NFATc1 and NF-kB (immunohistochemistry). In vitro, RAW 264.7 were treated with Chalcone T4 and stimulated with RANKL for assessment of osteoclast differentiation (actin ring staining) and activity (pit assay). RESULTS: Chalcone T4 significantly reduced periodontitis-associated bone resorption, as well as the cellular infiltrate, while increasing the collagen content. Production of TNF-α, infiltration of CD45-positive cells, and NF-kB activation were markedly reduced. In vitro, chalcone T4 inhibited both osteoclast differentiation and activity. CONCLUSION: Chalcone T4 significantly inhibited alveolar bone resorption and inflammation in vivo and RANKL-induced osteoclastogenesis in vitro, suggesting a therapeutic role for this compound in the treatment of periodontitis.
Asunto(s)
Pérdida de Hueso Alveolar , Resorción Ósea , Chalcona , Chalconas , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Animales , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/prevención & control , Diferenciación Celular , Chalcona/farmacología , Chalcona/uso terapéutico , Chalconas/farmacología , Chalconas/uso terapéutico , Ratones , Osteoclastos , Osteogénesis , Ligando RANK , RatasRESUMEN
BACKGROUND: Leukotrienes (LTs) participate in the process of tissue damage in periodontal disease by leukocyte chemotaxis and osteoclastic activation. The activation of Cysteinyl-LT receptor is associated with increased expression of proinflammatory molecules and osteoclastogenesis. However, its implications on periodontal disease progression have not been studied. The present study evaluated the effect of the cysteinyl-LT receptor antagonist (montelukast [MT]) on ligature-induced experimental periodontitis (EP) in rats. METHODS: Adult male Wistar rats were subjected to bilateral ligature-induced periodontitis and orally treated with MT (at doses of 10 or 30 mg/kg/d, MT10, and MT30, respectively). Sham animals had the ligatures immediately removed and received placebo treatment. Sets of animals were euthanized 7, 14, or 21 days after ligature placement and the mandibles were removed for macroscopic evaluation of alveolar bone loss (ABL). In addition, histological analysis of periodontal tissues, myeloperoxidase (MPO) activity of gingival tissues, and periodontal tissue expression of collagen type I, RUNX2, RANK, RANKL, OPG, BLT1, Cys-LTR1, LTA4H, and LTC4S were also analyzed. RESULTS: MT significantly reduced ABL at 14 (MT10 and MT30) and 21 days (MT10) (P < 0.05), gingival MPO at 7 (MT10) and 14 days (MT30) (P < 0.05), LTA4H, BLT1 and LTC4S gene expression on day 14 day (MT30, P < 0.05) and increased RUNX2 expression on day 14 (MT30, P < 0.05). CONCLUSION: Systemic therapy with MT decreases periodontal inflammation and ABL in ligature-induced periodontitis in rats.
Asunto(s)
Pérdida de Hueso Alveolar , Periodontitis , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Animales , Inflamación , Antagonistas de Leucotrieno , Masculino , Periodontitis/tratamiento farmacológico , Ratas , Ratas WistarRESUMEN
BACKGROUND: Periodontal pathogenesis takes into consideration that disease results from a complex inflammatory immune response. Among the major cytokines related to periodontal damage, interleukin (IL)-6 enhances a cascade of tissue destruction. Tocilizumab (TCZ) is a humanized monoclonal anti-human IL-6 receptor that inhibits IL-6-mediated proinflammatory activity. This study aimed to elucidate whether TCZ inhibits the deleterious effect of ligature-induced periodontitis. METHODS: Experimental ligature-induced periodontitis was treated with systemic administration of TCZ intraperitoneally in three different concentration dosages (2 mg/kg, 4 mg/kg, and 8 mg/kg. Euthanasia occurred at 7 and 14 days after the initiation of the study. Local changes in the alveolar bone were measured by bone volume, the ratio of bone volume, and trabecular thickness using microcomputed tomography. Attachment loss and inflammatory infiltrate were evaluated by histology. Immune response was analyzed focusing on the Th17 pattern. RESULTS: TCZ inhibited alveolar bone resorption and attachment loss in 7 and 14 days for all dosage groups in comparison to controls (P < 0.05). Besides, TCZ induced lower expression of inflammatory infiltrate (P <0.05) and less production of Th17-related cytokines (P <0.05) and RANKL (P <0.05). CONCLUSIONS: The inhibition of IL-6-mediated proinflammatory activity by IL-6R blocking reduced alveolar bone resorption and attachment loss supported by the modulation of the Th17 periodontal response. Considering the inflammatory status, modulatory therapy may be a promising approach to periodontal disease.