RESUMO
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.
Assuntos
Perda do Osso Alveolar , Periodontite , Humanos , Ratos , Masculino , Animais , Ratos Wistar , Leucócitos Mononucleares/metabolismo , Interleucina-10/uso terapêutico , Metaloproteinase 9 da Matriz , Periodontite/metabolismo , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/metabolismo , Modelos Animais de DoençasRESUMO
BACKGROUND: Desipramine is a tricyclic antidepressant with immune-modulatory activity, whose effects on ligature-induced periodontitis are yet to be investigated. Hence, its actions on alveolar bone resorption, gingival collagen content and key inflammatory mediators were herewith analyzed. METHODS: A total of 60 male Wistar rats were randomly assigned into three groups: 1) control: rats without ligature treated with vehicle (saline); 2) ligature: rats with ligature-induced periodontitis treated with vehicle; 3) ligature + desipramine: rats with ligature-induced periodontitis treated with desipramine (20 mg/kg/d in vehicle). Mandibles and gingival tissues were collected 3 or 15 days after ligature insertion (or no ligature insertion for controls) and treatments. Alveolar bone resorption and gingival collagen fibers were histologically analyzed using either HE or picrosirius red staining. Gingival mRNA expressions of interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 were obtained through reverse transcription polymerase chain reaction. MMP-9 activity was analyzed by zymography. RESULTS: Alveolar bone loss was significantly reduced in the ligature + desipramine group (P < 0.05), whereas gingival collagen degradation was like the ligature group (P > 0.05). Desipramine administration downregulated mRNA expressions of IL-1ß, iNOS, COX-2, and TIMP-1 when compared to vehicle alone in the ligature group (P < 0.05). MMP-9 expression and MMP-9/TIMP-1 ratio were similar among rats with ligature-induced periodontitis (P > 0.05); however, MMP-9 activity was lower in the group treated with desipramine (P < 0.05). CONCLUSION: Desipramine administration reduced alveolar bone loss as histologically observed, and modulated key bone remodeling and inflammatory mediators in rats with ligature-induced periodontitis.
Assuntos
Perda do Osso Alveolar , Periodontite , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Animais , Desipramina/farmacologia , Desipramina/uso terapêutico , Modelos Animais de Doenças , Gengiva , Masculino , Periodontite/tratamento farmacológico , Ratos , Ratos WistarRESUMO
BACKGROUND: Subantimicrobial dose doxycycline (SDD) has been used as an adjunct in periodontal treatment because of its matrix metalloproteinase inhibition properties. Although the benefits of SDD therapy, such as improvement in the parameters of periodontal probing depth and clinical attachment level, have been proven in multiple clinical studies, the comprehension of other biologic mechanisms of action on periodontitis remains poorly investigated. Therefore, this animal-model study evaluated the effects of SDD monotherapy on the expressions of the following key proinflammatory genes: proteinase-activated receptor-2 (PAR2), tumor necrosis factor (TNF)-α, interleukin (IL)-17, and IL-1ß. METHODS: Male Wistar rats were assigned randomly to the following: 1) control group: no ligature-induced periodontitis and no treatment; 2) ligature group: ligature-induced periodontitis and placebo treatment; and 3) ligature + doxycycline group: ligature-induced periodontitis and SDD treatment. After the experimental time, animals were sacrificed, and reverse transcription-polymerase chain reaction was performed to analyze the mRNA expression of IL-1ß, IL-17, TNF-α, and PAR2 in gingival tissue samples. Histologic analyses were performed on the furcation region and mesial gingiva of mandibular first molars to measure periodontal bone loss and collagen content. RESULTS: SDD administration significantly downregulated PAR2, IL-17, TNF-α, and IL-1ß mRNA expressions (P <0.05). In addition, SDD treatment was accompanied by lower rates of alveolar bone loss (P <0.05) and maintenance of the amount of gingival collagen fibers. CONCLUSION: These findings reveal new perspectives regarding SDD efficacy because it can be partially related to proinflammatory gene expression modulation, even considering PAR2 and IL-17, which has not been investigated thus far.
Assuntos
Periodontite , Animais , Antibacterianos , Regulação para Baixo , Doxiciclina , Interleucina-17 , Masculino , Ratos , Ratos Wistar , Receptor PAR-2RESUMO
BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, has been found recently to possess anti-inflammatory properties. The present study investigates the effects of fluoxetine on inflammatory tissue destruction in a rat model of ligature-induced periodontal disease. METHODS: Thirty male Wistar rats were randomly assigned into three groups (n = 10 animals per group): 1) control rats (without ligature); 2) rats with ligature + placebo (saline; oral gavage); and 3) rats with ligature + fluoxetine (20 mg/kg/day in saline; oral gavage). Histologic analyses were performed on the furcation region and mesial aspect of mandibular first molars of rats sacrificed at 15 days after ligature-induced periodontal disease. Reverse transcription-polymerase chain reaction and zymography were performed to analyze the mRNA expression of interleukin (IL)-1ß, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase and the MMP-9 activity, respectively, in gingival tissues samples. RESULTS: Compared to the ligature + placebo group, alveolar bone loss was reduced in the fluoxetine group (P <0.05), and the amount of collagen fibers in the gingival tissue was maintained. Moreover, in gingival tissue sampled 3 days after ligature attachment, fluoxetine administration reduced IL-1ß and COX-2 mRNA expression. Fluoxetine downregulated MMP-9 activity, without affecting MMP-9 mRNA expression induced by ligature, compared to the ligature + placebo group (P <0.05). These data suggest that fluoxetine suppressed proinflammatory responses, as well as proteolytic enzyme activity, induced by ligature. CONCLUSION: In the present study, fluoxetine suppresses the inflammatory response and protects against periodontal bone resorption and destruction of collagen fibers, suggesting that fluoxetine can constitute a promising therapeutic approach for periodontal diseases.
Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Fluoxetina/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Periodontite/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Perda do Osso Alveolar/metabolismo , Animais , Ciclo-Oxigenase 2/biossíntese , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Eletroforese em Gel de Poliacrilamida/métodos , Colágenos Fibrilares/análise , Gengiva/metabolismo , Interleucina-1beta/biossíntese , Ligadura , Masculino , Metaloproteinase 9 da Matriz/biossíntese , Inibidores de Metaloproteinases de Matriz , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/biossíntese , Periodontite/metabolismo , Ratos , Ratos Wistar , Técnicas de Cultura de TecidosRESUMO
Fluoxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been found to possess immune modulation effects, in addition to its antidepressant effects. However, it remains unclear whether SSRIs can suppress the antigen-presenting function of dendritic cells (DCs). Therefore, Fluoxetine was applied to a co-culture of Aggregatibacter actinomycetemcomitans (Aa)-reactive T cells (×Aa-T) isolated from Aa-immunized mice and DCs. This resulted in the suppressed proliferation of ×Aa-T stimulated with Aa-antigen presentation by DCs. Specifically, Fluoxetine increased the extracellular 5-hydroxytryptamine (5-HT) in the ×Aa-T/DC co-culture, whereas exogenously applied 5-HT promoted T-cell proliferation in the ×Aa-T/DC co-culture, indicating that Fluoxetine-mediated suppression of ×Aa-T/DC responses cannot be attributed to extracellular 5-HT. Instead, Fluoxetine remarkably suppressed the expression of costimulatory molecule ICOS-L on DCs. Fluoxetine also promoted a greater proportion of CD86(Low) immature DCs than CD86(High) mature DCs, while maintaining the expression levels of CD80, MHC-class-II and PD-L1. These results suggested that Fluoxetine suppressed the ability of DCs to present bacterial antigens to T cells, and the resulting T-cell proliferation, in a SERT/5-HT-independent manner and that diminished expression of ICOS-L on DCs and increase of CD86(Low) immature DCs caused by Fluoxetine might be partially associated with Fluoxetine-mediated suppression of DC/T-cell responses.
Assuntos
Apresentação de Antígeno/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Animais , Antígeno B7-2 , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Citocinas/imunologia , Desipramina/farmacologia , Fluoxetina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Serotonina/metabolismoRESUMO
7-Epiclusianone (7-epi), a novel naturally occurring compound isolated from Rheedia brasiliensis, effectively inhibits the synthesis of exopolymers and biofilm formation by Streptococcus mutans. In the present study, the ability of 7-epi, alone or in combination with fluoride (F), to disrupt biofilm development and pathogenicity of S. mutans in vivo was examined using a rodent model of dental caries. Treatment (twice-daily, 60s exposure) with 7-epi, alone or in combination with 125 ppm F, resulted in biofilms with less biomass and fewer insoluble glucans than did those treated with vehicle-control, and they also displayed significant cariostatic effects in vivo (p < 0.05). The combination 7-epi + 125 ppm F was as effective as 250 ppm F (positive-control) in reducing the development of both smooth- and sulcal-caries. No histopathological alterations were observed in the animals after the experimental period. The data show that 7-epiclusianone is a novel and effective antibiofilm/anticaries agent, which may enhance the cariostatic properties of fluoride.