RESUMO
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.
Assuntos
Perda do Osso Alveolar , Periodontite , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Animais , Inflamação , Antagonistas de Leucotrienos , Masculino , Periodontite/tratamento farmacológico , Ratos , Ratos WistarRESUMO
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
In the present study we analyzed morphological and metabolic alterations in dams nursing small litters and their consequences to offspring throughout lactation. Offspring sizes were adjusted to Small Litter (SL, 3 pups/ dam) and Normal Litter (NL, 9 pups/ dam). Body weight, food intake, white adipose tissue (WAT) content, histological analysis of the pancreas, mammary gland (MG) and brown adipose tissue (BAT) as well as, plasma parameters and milk composition were measured in dams and pups on the 7th, 14th and 21st days of lactation. In general, SL-dams presented higher body weight and retroperitoneal fat content, elevated fat infiltration in BAT, reduced islets size and hyperglycemia throughout lactation in relation to NL-dams (p<0.05). Moreover, MG from SL-dams had reduced alveoli development and high adipocytes content, resulting in milk with elevated energetic value and fat content in relation to NL-dams (p<0.05). Maternal states influenced offspring anthropometric conditions during lactation, offspring-SL displayed higher body weight and growth, hyperglycemia, augmented lipid deposition in BAT and elevated islet. Thus, maternal histological and metabolic changes are due to modifications to nursing small litters and reinforce the importance of preserving maternal health during lactation avoiding early programming effects on offspring preventing metabolic consequences later in life.
Assuntos
Tecido Adiposo/metabolismo , Lactação/metabolismo , Tamanho da Ninhada de Vivíparos/fisiologia , Leite/química , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Peso Corporal , Ingestão de Alimentos , Feminino , Ilhotas Pancreáticas/anatomia & histologia , Masculino , Glândulas Mamárias Animais/anatomia & histologia , Modelos Animais , Gravidez , 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: New drugs for the treatment of diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists and inhibitors of dipeptidyl peptidase-4 (DPP-4) have shown pleiotropic effects on bone metabolism and anti-inflammatory properties. The aim of this study is to evaluate the effects of exenatide (GLP-1 agonist) and sitagliptin (DPP-4 inhibitor) during periodontitis induction by ligature insertion in rats. METHODS: Forty rats were divided into four groups: 1) animals with induced periodontitis that received exenatide (EG); 2) animals with induced periodontitis that received sitagliptin (SG); 3) animals with induced periodontitis and without drug treatment (LG); and 4) animals without induced periodontitis and without drug treatment (controls). The drugs were administered for 28 days. On the day the animals were sacrificed, blood was collected for analysis of glucose and DPP-4 levels. The gene expressions of prostaglandin-endoperoxide synthase 2, tissue inhibitor of metalloproteinase 1, Dpp4, nitric oxide synthase 2 (Nos2), interleukin 1ß (Il1b), and matrix metalloproteinase 9 (Mmp9) in the gingiva; support and alveolar bone loss; connective tissue attachment; and the quantity of gingival collagen were evaluated. RESULTS: Exenatide and sitagliptin treatments have led to a lower percentage of weight gain but did not influence glycemia. Sitagliptin reduced the serum concentration of DPP-4. Interestingly, although the gene expression profile has revealed a downregulation of Mmp9, Nos2, and Il1b in both EG and SG compared to LG, a significant protective effect was not observed on alveolar bone and collagen tissue in this model. CONCLUSION: Regardless of the reduction of the expression of Il1b, Nos2, and Mmp9, the drugs were not effective in the stabilization or reduction of alveolar bone loss and collagen degradation in rats.
Assuntos
Perda do Osso Alveolar , Hipoglicemiantes/farmacologia , Peptídeos/farmacologia , Periodontite , Fosfato de Sitagliptina/farmacologia , Peçonhas/farmacologia , Animais , Exenatida , Interleucina-1beta/metabolismo , Metaloproteinase 9 da Matriz , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
BACKGROUND: There are few studies on periodontal status related to microbiologic and immunologic profiles among individuals not or occasionally using alcohol and those with alcohol dependence. The aim of this study is to determine the effect of alcohol consumption on the levels of subgingival periodontal pathogens and proinflammatory cytokines (interleukin [IL]-1ß and tumor necrosis factor [TNF]-α) in the gingival fluid among individuals with and without periodontitis. METHODS: This observational analytic study includes 88 volunteers allocated in four groups (n = 22): individuals with alcohol dependence and periodontitis (ADP), individuals with alcohol dependence and without periodontitis (ADNP), individuals not or occasionally using alcohol with periodontitis (NAP), and individuals not or occasionally using alcohol without periodontitis (NANP). Levels of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Eikenella corrodens, and Fusobacterium nucleatum were determined by real-time polymerase chain reaction on the basis of the subgingival biofilm, and IL-1ß and TNF-α were quantified by enzyme-linked immunosorbent assay in gingival fluid samples. RESULTS: Individuals with alcohol dependence showed worse periodontal status and higher levels of P. intermedia, E. corrodens, F. nucleatum, and IL-1ß than non-users. No significant correlations between TNF-α and bacterial levels were observed. However, in the ADP group, higher levels of E. corrodens were correlated with higher levels of IL-1ß. CONCLUSION: A negative influence of alcohol consumption was observed on clinical and microbiologic periodontal parameters, as well as a slight influence on immunologic parameters, signaling the need for additional studies.
Assuntos
Consumo de Bebidas Alcoólicas , Líquido do Sulco Gengival/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Interleucina-1beta/análise , Periodontite/microbiologia , Fator de Necrose Tumoral alfa/análise , Adulto , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Consumo de Bebidas Alcoólicas/imunologia , Alcoolismo/imunologia , Alcoolismo/microbiologia , Carga Bacteriana , Biofilmes , Estudos Transversais , Eikenella corrodens/isolamento & purificação , Feminino , Fusobacterium nucleatum/isolamento & purificação , Líquido do Sulco Gengival/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/imunologia , Porphyromonas gingivalis/isolamento & purificação , Prevotella intermedia/isolamento & purificaçãoRESUMO
In oral biofilms, two of the major environmental challenges encountered by the dental pathogen Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the S. mutans transcriptional regulators SpxA1 and SpxA2 (formerly SpxA and SpxB, respectively) are involved in stress survival by activating the expression of classic oxidative stress genes such as dpr, nox, sodA and tpx. We reasoned that some of the uncharacterized genes under SpxA1/A2 control are potentially involved in oxidative stress management. Therefore, the goal of this study was to use Spx-regulated genes as a tool to identify novel oxidative stress genes in S. mutans. Quantitative real-time PCR was used to evaluate the responses of ten Spx-regulated genes during H2O2 stress in the parent and Δspx strains. Transcription activation of the H2O2-induced genes (8 out of 10) was strongly dependent on SpxA1 and, to a lesser extent, SpxA2. In vitro transcription assays revealed that one or both Spx proteins directly regulate three of these genes. The gene encoding the FeoB ferrous permease was slightly repressed by H2O2 but constitutively induced in strains lacking SpxA1. Nine genes were selected for downstream mutational analysis but inactivation of smu127, encoding a subunit of the acetoin dehydrogenase was apparently lethal. In vitro and in vivo characterization of the viable mutants indicated that, in addition to the transcriptional activation of reducing and antioxidant pathways, Spx performs an important role in iron homeostasis by regulating the intracellular availability of free iron. In particular, inactivation of the genes encoding the Fe-S biogenesis SUF system and the previously characterized iron-binding protein Dpr resulted in impaired growth under different oxidative stress conditions, increased sensitivity to iron and lower infectivity in rats. These results serve as an entryway into the characterization of novel genes and pathways that allow S. mutans to cope with oxidative stress.
Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Streptococcus mutans/genética , Animais , Regulação Bacteriana da Expressão Gênica , Peróxido de Hidrogênio/farmacologia , Boca/microbiologia , Estresse Oxidativo , Ratos , Streptococcus mutans/isolamento & purificaçãoRESUMO
BACKGROUND: Although patients with diabetes are frequently affected by periodontitis, only a few investigations have focused on gingivitis in this at-risk population. This randomized placebo-controlled clinical trial compared the response to a gingivitis treatment protocol that combined mechanical procedures and daily use of an essential oil (EO) mouthrinse between patients with and without diabetes. METHODS: The whole-mouth periodontal probing depth (PD), gingival index (GI), and plaque index (PI) were monitored in gingivitis cases among systemically healthy patients (n = 60) or those with diabetes (n = 60) at baseline and 3 months after treatment. Levels of Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and total bacterial load were determined by a real-time polymerase chain reaction in intrasulci plaque samples. The volume of gingival crevicular fluid (GCF) was quantified, and interleukin-1ß (IL-1ß) levels were determined in GCF samples. After a full-mouth ultrasonic debridement, patients were randomly assigned to an EO or a placebo rinse for 90 days (40 mL/day). The data were analyzed through repeated-measures analysis of variance and multiple comparisons Tukey tests (P <0.05). RESULTS: GI was more severe in the diabetes group. Diabetes impaired GI and reduced GCF volume. PD, bacterial levels, and IL-1ß improved similarly in both systemic conditions. The adjunctive use of EO provided greater reductions of PI, GI, total bacterial load, T. forsythia, A. actinomycetemcomitans, and GCF volume. CONCLUSIONS: Response to gingivitis treatment in patients with diabetes can slightly differ from that in patients without diabetes. Daily use of an EO mouthrinse after ultrasonic debridement benefited patients with and without diabetes.
Assuntos
Complicações do Diabetes , Gengivite/terapia , Adulto , Aggregatibacter actinomycetemcomitans/efeitos dos fármacos , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Carga Bacteriana/efeitos dos fármacos , Bacteroides/efeitos dos fármacos , Bacteroides/isolamento & purificação , Placa Dentária/microbiologia , Índice de Placa Dentária , Complicações do Diabetes/imunologia , Complicações do Diabetes/microbiologia , Método Duplo-Cego , Feminino , Seguimentos , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/imunologia , Gengivite/imunologia , Gengivite/microbiologia , Humanos , Interleucina-1beta/análise , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais/uso terapêutico , Óleos Voláteis/uso terapêutico , Desbridamento Periodontal/métodos , Índice Periodontal , Bolsa Periodontal/classificação , Placebos , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/isolamento & purificação , Adulto JovemRESUMO
PURPOSE: To compare the pharmacokinetic profiles and to evaluate the bioequivalence of two commercial amoxicillin suspension formulations (500 mg/5 mL AMOXIL®, reference formulation and AMOXI-PED®, test formulation) in healthy Brazilian volunteers. METHODS: Under fasting condition, 25 volunteers (13 males and 12 females) were included in this randomized, open-label, two-period crossover (1-week washout interval) bioequivalence study. Blood samples were collected at pre-dose (0 hour) and 0.5, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 12 hours after drug ingestion. Pharmacokinetic parameters (Cmax, tmax, t1/2, AUC0-tlast, and AUC0-∞) were calculated from plasma concentrations for both formulations in each subject. RESULTS: Arithmetic mean values of the pharmacokinetic parameters were: Cmax = 12.004 (± 2.824) µg×mL-1; tmax = 1.118 (± 0.396) h; t1/2 = 1.226 (± 0.179) h; AUC0-tlast = 29.297 (± 6.007) µg×h×mL-1; and AUC0-∞ = 29.299 (± 6.007) µg×h×mL-1 for reference formulation and Cmax = 11.456 (± 2.825) µg×mL-1; tmax = 1.331 (± 0.509) h; t1/2 = 1.141 (± 0.133) h; AUC0-tlast = 28.672 (± 5.778) µg×h×mL-1; and AUC0-∞ = 28.693 (± 5.796) µg×h×mL-1 for test formulation. The confidence intervals (90% CI) for reference and test formulations were, respectively, 90.74 - 100.46% for Cmax and 93.62 - 103.61% for AUC0-t. CONCLUSION: Based on the results, both formulations of amoxicillin evaluated in this study were considered bioequivalent according to FDA and ANVISA/Brazil criteria.