RESUMO
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.
RESUMO
Chitosan is a naturally occurring polysaccharide obtained from chitin, present in abundance in the exoskeletons of crustaceans and insects. It has aroused great interest as a biomaterial for tissue engineering on account of its biocompatibility and biodegradation and its affinity for biomolecules. A significant number of research groups have investigated the application of chitosan as scaffolds for tissue regeneration. However, there is a wide variability in terms of physicochemical characteristics of chitosan used in some studies and its combinations with other biomaterials, making it difficult to compare results and standardize its properties. The current systematic review of literature on the use of chitosan for tissue regeneration consisted of a study of 478 articles in the PubMed database, which resulted, after applying inclusion criteria, in the selection of 61 catalogued, critically analysed works. The results demonstrated the effectiveness of chitosan-based biomaterials in 93.4% of the studies reviewed, whether or not combined with cells and growth factors, in the regeneration of various types of tissues in animals. However, the absence of clinical studies in humans, the inadequate experimental designs, and the lack of information concerning chitosan's characteristics limit the reproducibility and relevance of studies and the clinical applicability of chitosan.
Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Regeneração , Engenharia Tecidual , Alicerces Teciduais , Animais , Humanos , Reprodutibilidade dos TestesRESUMO
Periodontitis (PD) and rheumatoid arthritis (RA) are immunoinflammatory diseases where leukocyte infiltration and inflammatory mediators induce alveolar bone loss, synovitis, and joint destruction, respectively. Thus, we reviewed the relationship between both diseases considering epidemiological aspects, mechanical periodontal treatment, inflammatory mediators, oral microbiota, and antibodies, using the keywords "periodontitis" and "rheumatoid arthritis" in PubMed database between January 2012 and March 2015, resulting in 162 articles. After critical reading based on titles and abstracts and following the inclusion and exclusion criteria, 26 articles were included. In the articles, women over 40 years old, smokers and nonsmokers, mainly constituted the analyzed groups. Eight studies broached the epidemiological relationship with PD and RA. Four trials demonstrated that the periodontal treatment influenced the severity of RA and periodontal clinical parameters. Nine studies were related with bacteria influence in the pathogenesis of RA and the presence of citrullinated proteins, autoantibodies, or rheumatoid factor in patients with PD and RA. Five studies investigated the presence of mediators of inflammation in PD and RA. In summary, the majority of the articles have confirmed that there is a correlation between PD and RA, since both disorders have characteristics in common and result from an imbalance in the immunoinflammatory response.
Assuntos
Artrite Reumatoide/metabolismo , Periodontite/metabolismo , Animais , Artrite Reumatoide/imunologia , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Periodontite/imunologia , Fator Reumatoide/metabolismoRESUMO
OBJECTIVE: Calotropis procera latex protein (CpLP) is a popular anti-inflammatory and therefore we aimed to study its effects on inflammatory bone loss. DESIGN: Male Wistar rats were subjected to a ligature of molars. Groups of rats received intraperitoneally CpLP (0.3 mg/kg, 1 mg/kg, or 3 mg/kg) or saline (0.9% NaCl) one hour before ligature and then daily up to 11 days, compared to naïve. Gingiva was evaluated by myeloperoxidase activity and interleukin-1 beta (IL-1ß) expression by ELISA. Bone resorption was evaluated in the region between the cement-enamel junction and the alveolar bone crest. The histology considered alveolar bone resorption and cementum integrity, leukocyte infiltration, and attachment level, followed by immunohistochemistry bone markers between 1st and 2nd molars. Systemically, the weight of the body and organs, and a leukogram were performed. RESULTS: The periodontitis significantly increased myeloperoxidase activity and the IL-1ß level. The increased bone resorption was histologically corroborated by periodontal destruction, leukocyte influx, and attachment loss, as well as the increasing receptor activator of the nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio, and Tartrate-resistant acid phosphatase (TRAP)+ cells when compared to naïve. CpLP significantly reduced myeloperoxidase activity, level of IL-1ß, alveolar bone resorption, periodontal destruction, leukocyte influx, and attachment loss. The CpLp also reduced the RANKL/OPG ratio and TRAP+ cells, when compared with the saline group, and did not affect the systemic parameters. CONCLUSIONS: CpLP exhibited a periodontal protective effect by reducing inflammation and restricting osteoclastic alveolar bone resorption in this rat model.
Assuntos
Perda do Osso Alveolar , Calotropis , Ratos , Masculino , Animais , Ratos Wistar , Látex/farmacologia , Peroxidase , Calotropis/metabolismo , Inflamação/prevenção & controle , Perda do Osso Alveolar/patologia , Osteoprotegerina/farmacologia , Processo Alveolar/metabolismo , Antioxidantes , Ligante RANK/metabolismoRESUMO
BACKGROUND: Members of the botanical families Apiaceae/Umbelliferae, Asteraceae, Fabaceae/Leguminosae, and Thymelaeaceae are rich in coumarins and have traditionally been used as ethnomedicines in many regions including Europe, Asia, and South America. Coumarins are a class of secondary metabolites that are widely present in plants, fungi, and bacteria and exhibit several pharmacological, biochemical, and therapeutic effects. Recently, many plants rich in coumarins and their derivatives were found to affect bone metabolism. OBJECTIVE: To review scientific literature describing the mechanisms of action of coumarins in osteoclastogenesis and bone resorption. MATERIALS AND METHODS: For this systematic review, the PubMed, Scopus, and Periodical Capes databases and portals were searched. We included in vitro research articles published between 2010 and 2020 that evaluated coumarins using osteoclastogenic markers. RESULTS: Coumarins have been reported to downregulate RANKL-RANK signaling and various downstream signaling pathways required for osteoclast development, such as NF-κB, MAPK, Akt, and Ca2+ signaling, as well as pathways downstream of the nuclear factor of activated T-cells (NFATc1), including tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and matrix metalloproteinase 9 (MMP-9). CONCLUSIONS: Coumarins primarily inhibit osteoclast differentiation and activation by modulating different intracellular signaling pathways; therefore, they could serve as potential candidates for controlled randomized clinical trials aimed at improving human bone health.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Cumarínicos/farmacologia , Ligante RANK/fisiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Células Cultivadas , Humanos , Osteogênese/efeitos dos fármacos , Receptor Ativador de Fator Nuclear kappa-B/fisiologiaRESUMO
The molecular weight of chitosan (CS) may affect its physical properties and its ability to induce an appropriate host response. The biocompatibilities of CS membranes of low (LMWCS) and high (HMWCS) molecular weight were investigated by inserting these materials into the subcutaneous tissue of rats for 1-28 days and evaluating leukocyte infiltration, granulation tissue, fibrosis, arginase-1 immunostaining, as well as nuclear factor-κB (NF-κΒ) and fibroblast growth factor (FGF)-2 expressions. Both CS membranes induced a peak of leukocyte infiltration on the first day of insertion and stimulated granulation and fibrous tissue generation when compared to control. LMWCS induced more collagen deposition a week earlier, when compared to the control and HMWCS membrane. The membranes also increased arginase-1 immunostaining, a M2 macrophage marker. M2 macrophage is recognized as anti-inflammatory and pro-regenerative. NF-κB is an essential biomarker of the inflammatory process and induces the expression of several pro-inflammatory cytokines. The LMWCS membrane reduced inflammation, as indicated by a reduced nucleus/cytoplasm NF-κB ratio in surrounding tissue from days 7 to 14 when compared to control. On the first day, the expression of FGF-2, a biomarker of inflammatory resolution, was increased in the tissue of the LWMCS group, when compared with HMWCS, which was consistent with the type I collagen deposition. Thus, LWMCS was associated with a prior reduction of the inflammatory response and improved wound healing.
Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Quitosana/química , Quitosana/toxicidade , Inflamação/induzido quimicamente , Animais , Arginase/metabolismo , Colágeno/metabolismo , Citocinas , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibrose , Tecido de Granulação/patologia , Inflamação/patologia , Leucócitos/patologia , Masculino , Peso Molecular , NF-kappa B/metabolismo , Ratos , Ratos Wistar , CicatrizaçãoRESUMO
Researchers see algae as a promising tool to discover both efficient and safe agents for pain therapy. We evaluated the antinociceptive and anti-inflammatory activities of lectin from the marine alga Pterocladiella capillacea lectin (PcL). PcL was purified and tested in classical models of nociception and inflammation. Male Swiss mice received PcL 30 min prior to receiving 0.8% acetic acid (10 microl/10 g, i.p.), 1% formalin (20 microl/intraplantar) or the hot plate test, and were compared to untreated animals or animals pretreated with indomethacin or morphine. PcL (0.9, 8.1 or 72.9 mg/kg, i.v.) significantly reduced the number of writhes (30%, 39%, and 52%, respectively). PcL (72.9 mg/kg, i.v.) also reduced (p<0.05) both the first and second phases of the formalin test by 58% and 87%, respectively. However, PcL (72.9 mg/kg) did not present significant antinociceptive effects in the hot plate test when compared to morphine, suggesting that its antinociceptive action occurs via peripheral rather than a central-acting mechanism. It was also observed that leukocyte migration was induced by carrageenan (500 microg/cavity) in male Wistar rats and that PcL (8.1 mg/kg, i.v.) significantly reduced neutrophil migration by 84%, as compared to untreated animals, suggesting inhibition of inflammatory mediators. The data indicated that PcL has peripheral actions with both anti-inflammatory and antinociceptive properties.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Lectinas/uso terapêutico , Leucócitos/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Rodófitas/química , Ácido Acético , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Carragenina , Modelos Animais de Doenças , Formaldeído , Temperatura Alta , Indometacina , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/imunologia , Mediadores da Inflamação/antagonistas & inibidores , Lectinas/farmacologia , Masculino , Camundongos , Morfina , Dor/induzido quimicamente , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
BACKGROUND: The genus Uncaria (Rubiaceae) has several biological properties significant to human health. However, the mechanisms underlying the protective effect of this plant on bone diseases are uncertain. PURPOSE: The present study investigated the role of Uncaria tomentosa extract (UTE) on alveolar bone loss in rats and on osteoclastogenesis in vitro. MATERIALS: UTE was characterized by an Acquity UPLC (Waters) system, coupled to an Electrospray Ionization (ESI) interface and Quadrupole/Flight Time (QTOF, Waters) Mass Spectrometry system (MS). The effect of UTE treatment for 11 days on the ligature-induced bone loss was assessed focusing on several aspects: macroscopic and histological analysis of bone loss, neutrophil and osteoclast infiltration, and anabolic effect. The effect of UTE on bone marrow cell differentiation to osteoclasts was assessed in vitro. RESULTS: The analysis of UTE by UPLC-ESI-QTOF-MS/MS identified 24 compounds, among pentacyclic or tetracyclic oxindole alkaloids and phenols. The administration of UTE for 11 days on ligature-induced rat attenuated the periodontal attachment loss and alveolar bone resorption. It also diminished neutrophil migration to the gingiva tissue, demonstrated by a lower level of MPO. UTE treatment also decreased the level of RANKL/OPG ratio, the main osteoclast differentiation-related genes, followed by reduced TRAP-positive cell number lining the alveolar bone. Additionally, the level of bone-specific alkaline phosphatase, an anabolic bone marker, was elevated in the plasma of UTE treated rats. Next, we determined a possible direct effect of UTE on osteoclast differentiation in vitro. The incubation of primary osteoclast with UTE decreased RANKL-induced osteoclast differentiation without affecting cell viability. This effect was supported by downregulation of the nuclear factor activated T-cells, cytoplasmic 1 expression, a master regulator of osteoclast differentiation, and other osteoclast-specific activity markers, such as cathepsin K and TRAP. CONCLUSION: UTE exhibited an effective anti-resorptive and anabolic effects, which highlight it as a potential natural product for the treatment of certain osteolytic diseases, such as periodontitis.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/tratamento farmacológico , Unha-de-Gato/química , Extratos Vegetais/farmacologia , Perda do Osso Alveolar/tratamento farmacológico , Animais , Conservadores da Densidade Óssea/química , Células da Medula Óssea/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Regulação para Baixo/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoprotegerina/metabolismo , Periodontite/tratamento farmacológico , Periodontite/etiologia , Extratos Vegetais/química , Ligante RANK/metabolismo , Ratos Wistar , Espectrometria de Massas em TandemRESUMO
The authors investigated the antinociceptive activity of sildenafil and adrenergic agents co-administered in the writhing test in mice. The intensity of nociception was quantified by the number of writhes occurring between 0 and 30 min after stimulus injection. Nontreated groups (NT) received acid intraperitoneally (ip) followed by sterile saline (ip). Animals received (ip) sildenafil (2.5 or 5 mg/kg), propranolol (0.5 or 2 mg/kg), atenolol (0.05 or 2 mg/kg), prazosin (0.05 or 0.25 mg/kg) or clonidine (0.01 or 0.1 mg/kg) 30 min before acid injection. It was observed that only the largest doses of every drug inhibited the number of writhes in mice. In another series of experiments, animals were pretreated with the lower ineffective doses of propranolol, atenolol, prazosin or clonidine. After 30 min, mice also received the lower ineffective dose of sildenafil followed by acid injection. The combination of ineffective doses of propranolol, atenolol, prazosin or clonidine with sildenafil significantly inhibited the nociceptive response induced by acetic acid injection. Data obtained from these experiments showed that ineffective doses of sildenafil associated with ineffective doses of adrenergic agents provided analgesic effects in the writhing test.
Assuntos
Adrenérgicos/farmacologia , Medição da Dor/métodos , Dor/tratamento farmacológico , Piperazinas/farmacologia , Sulfonas/farmacologia , Ácido Acético , Animais , Atenolol/farmacologia , Clonidina/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Indometacina/farmacologia , Masculino , Camundongos , Dor/induzido quimicamente , Dor/fisiopatologia , Inibidores da Fosfodiesterase 5 , Prazosina/farmacologia , Propranolol/farmacologia , Purinas/farmacologia , Citrato de SildenafilaRESUMO
AIMS: The aim of the present study was to investigate the presence of immunoglobulins (Ig) in whole saliva from patients affected by autoimmune hepatitis (AIH). DESIGN: Twelve individuals with AIH and 12 healthy individuals without (CON) autoimmune hepatitis, aged 8-18 years, participated in this study. Non-stimulated whole saliva was collected and centrifuged. Supernatants were separated and lyophilized. Salivary pH was measured and immunoglobulins were analyzed through ELISA technique. RESULTS: Salivary pH (CON, 7.17⯱â¯0.45; AIH, 6.92⯱â¯0.43) did not differ between groups (pâ¯=â¯0.183). Measurable levels of IgG, IgA, IgM and IgE were detected on all patients. IgG levels were higher in AIH individuals (CON, 1.058⯱â¯0.386; AIH, 1.635⯱â¯0.373; pâ¯=â¯0.001), whereas IgA (CON, 0.915⯱â¯0.187; AIH, 0.995⯱â¯0.235; pâ¯=â¯0.362), IgM (CON, 0.683⯱â¯0.147, AIH, 0.646⯱â¯0.161; pâ¯=â¯0.561) and IgE levels (CON, 1.241⯱â¯0.378; AIH, 1.312⯱â¯0.412; pâ¯=â¯0.664) did not present differences between groups. CONCLUSIONS: The results of the present study suggest differences in salivary IgG levels between individuals with and without AIH. Thus, saliva has the potential of becoming an important diagnostic tool for the assessment of AIH.
Assuntos
Hepatite Autoimune/imunologia , Hipergamaglobulinemia/imunologia , Imunoglobulinas/análise , Imunoglobulinas/imunologia , Saliva/química , Adolescente , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Concentração de Íons de Hidrogênio , Imunoglobulina G/análise , Imunoglobulina G/imunologia , MasculinoRESUMO
Seselin an angular pyranocoumarin at dose of 0.5, 4.5 or 40.5 mg/kg inhibited the writhing response induced by acetic acid in a significant and dose-dependent manner, by 19.5%, 26.2% and 41.4%, respectively. Using the same doses, seselin elicited a significant inhibition of formalin response during the second phase (inflammatory), by 90.3%, 97.8% and 95.3%, respectively. Besides, a significant reduction of licking time was observed during the first phase (neurogenic) at the highest doses of seselin, by 34.4% and 66.9%, respectively. On the contrary, in the hot plate test no effect was observed after seselin treatment. In conclusion, seselin was able to inhibit inflammatory hyperalgesia, suggesting that this natural product possesses both important peripheral anti-inflammatory and antinociceptive properties.
Assuntos
Analgésicos/farmacologia , Cumarínicos/farmacologia , Dor/prevenção & controle , Fitoterapia , Extratos Vegetais/farmacologia , Piranos/farmacologia , Rutaceae , Ácido Acético , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Animais , Cumarínicos/administração & dosagem , Cumarínicos/uso terapêutico , Relação Dose-Resposta a Droga , Formaldeído , Temperatura Alta , Masculino , Camundongos , Dor/induzido quimicamente , Medição da Dor/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Piranocumarinas/administração & dosagem , Piranocumarinas/farmacologia , Piranocumarinas/uso terapêutico , Piranos/administração & dosagem , Piranos/uso terapêuticoRESUMO
The aim of this study was to evaluate the anti-inflammatory and anti-resorptive effect of atorvastatin (ATV) in an experimental alveolar bone loss (ABL) model. Wistar rats were subjected to ligature placement around the maxillary second molar for 11 days. The animals received 0.9% saline (2 mL/kg) or ATV (0.3, 3 or 27 mg/kg) daily by gavage. ABL was evaluated by resorption area and histopathological analysis. Serum bone-specific alkaline phosphatase (BALP) activity was also evaluated. Leukogram was performed at 0 h, 6th h, 2nd, 7th and 11th days. Kidney and liver conditions and the body mass variation were analyzed. ATV (3 and 27 mg/kg) inhibited ABL by 39% and 56%, respectively. Histopathological analysis showed that ATV 27 mg/kg prevented ABL and cemental resorption, and inflammatory cell infiltration induced by ligature. ATV (27 mg/kg) prevented serum BALP levels reduction. ATV (27 mg/kg) prevented leukocytosis and did not affect either kidney or liver function nor body mass weight. ATV showed a protecting effect in the ligature-induced periodontitis, without affecting system parameters, by inhibition of inflammatory process and by its anabolic activity on the alveolar bone.
Assuntos
Perda do Osso Alveolar , Anti-Inflamatórios/farmacologia , Atorvastatina/farmacologia , Reabsorção Óssea/prevenção & controle , Fosfatase Alcalina/metabolismo , Animais , Osso e Ossos/enzimologia , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND: Matricaria recutita L. (chamomile) has demonstrated anti-inflammatory activity. Accordingly, the ability of the Matricaria recutita extract (MRE) to inhibit proinflammatory cytokines and its influence on alveolar bone resorption (ABR) in rats. METHODS: Wistar rats were subjected to ABR by ligature with nylon thread in the second upper-left molar, with contralateral hemiarcade as control. Rats received polysorbate TW80 (vehicle) or MRE (10, 30, and 90 mg/kg) 1 hour before ligature and daily until day 11. The periodontium was analyzed by macroscopy, histometry, histopathology, and immunohistochemistry for the receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP). The gingival tissue was used to quantify the myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels by enzyme-linked immunosorbent assay. Blood samples were collected to evaluate bone-specific alkaline phosphatase (BALP), leukogram, and dosages of aspartate and alanine transaminases, urea, and creatinine. Aspects of liver, kidneys, spleen, and body mass variations were also evaluated. RESULTS: The 11 days of ligature induced bone resorption, low levels of BALP, leukocyte infiltration; increase of MPO, TNF-α, and IL-1ß; immunostaining increase for RANKL and TRAP; reduction of OPG and leukocytosis, which were significantly prevented by MRE, except for the low levels of BALP and the leukocytosis. Additionally, MRE did not alter organs or body weights of rats. CONCLUSION: MRE prevented the inflammation and ABR by reducing TNF-α and IL-1ß, preventing the osteoclast activation via the RANKL-OPG axis, without interfering with bone anabolism.
Assuntos
Perda do Osso Alveolar , Reabsorção Óssea , Camomila/química , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Interleucina-1beta , Matricaria , Osteoclastos , Osteoprotegerina , Periodontite , Ligante RANK , Ratos , Ratos WistarRESUMO
S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1ß levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease.
Assuntos
Derivados da Hipromelose/administração & dosagem , Doenças Periodontais/tratamento farmacológico , S-Nitrosoglutationa/administração & dosagem , Administração Tópica , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Animais , Modelos Animais de Doenças , Gengiva/efeitos dos fármacos , Gengiva/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Masculino , Doadores de Óxido Nítrico/administração & dosagem , Óxido Nítrico Sintase Tipo II/metabolismo , Doenças Periodontais/metabolismo , Doenças Periodontais/patologia , Ratos , Ratos Wistar , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Soluções , Fosfatase Ácida Resistente a Tartarato/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0153716.].
RESUMO
The aim of this study was to evaluate the bone regenerative effect of glutaraldehyde (GA) cross-linking on mineralized polyanionic collagen membranes in critical-sized defects on rat calvarias. Bone calvarial defects were induced in Wistar rats, which were then divided into five groups: a sham group; a control group, which received a commercial membrane; and GA, 25GA, and 75GA groups, which received one of three different polyanionic collagen membranes mineralized by 0, 25, or 75 hydroxyapatite cycles and then cross-linked by GA. Bone formation was evaluated based on digital radiography and computerized tomography. Histological analyses were performed 4 and 12 weeks after the surgical procedure to observe bone formation, membrane resorption, and fibrous tissue surrounding the membranes. Measurement of myeloperoxidase activity, tumor necrosis factor alpha, and interleukin 1beta production was performed 24 h after surgery. The percentage of new bone formation in the GA, 25GA, and 75GA groups was higher compared with the control and sham groups. In the GA and 25 GA groups, the membranes were still in place and were contained in a thick fibrous capsule after 12 weeks. No significant difference was found among the groups regarding myeloperoxidase activity and interleukin 1beta levels, although the GA, 25GA, and 75GA groups presented decreased levels of tumor necrosis factor alpha compared with the control group. These new GA cross-linked membranes accelerated bone healing of the calvarium defects and did not induce inflammation. In addition, unlike the control membrane, the experimental membranes were not absorbed during the analyzed period, so they may offer advantages in large bone defects where prolonged membrane barrier functions are desirable.
Assuntos
Regeneração Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Colágeno/farmacologia , Consolidação da Fratura/efeitos dos fármacos , Membranas Artificiais , Osteogênese/efeitos dos fármacos , Crânio/lesões , Animais , Colágeno/química , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/biossíntese , Peroxidase/biossíntese , Ratos , Ratos Wistar , Crânio/diagnóstico por imagem , Crânio/metabolismo , Tomografia Computadorizada por Raios X , Fator de Necrose Tumoral alfa/biossínteseRESUMO
PURPOSE: To design a novel model to study Cobalt-60 (Co-60)-induced radiation mucositis and to describe the pathways involved in its development. MATERIALS AND METHODS: Hamsters' cheeks were treated with Co-60 radiation (10, 20, 30 or 35 Gy). Three days later, oral mucosa scarification was performed with a needle. The animals were euthanized at day 13 (D + 13) after irradiation. Gross and microscopic alterations were evaluated by a new score system that we developed. Also, neutrophil infiltration, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-10, inducible nitric oxide synthase (iNOS), nitric oxide (NO) and nitrite were assessed in oral mucosa. We also tried to establish the roles of TNF-α and IL-1ß and iNOS in our model using pharmacological approaches with pentoxiphylline (PTX) and aminoguanidine (AMG), respectively. RESULTS: We found that a single administration of 35 Gy of Co-60, followed by mechanical scratches 3 days later, induced oral mucositis in hamsters. Animals with mucositis lost weight and had a survival median of 13 days, the time at which peak inflammation occurs. We noticed increased levels of NO, iNOS, TNF-α and IL-1ß and a reduced concentration of IL-10. PTX partially prevented the mucositis phenotype by reducing the levels of inflammatory mediators and iNOS expression. Additionally, AMG, a selective inhibitor of iNOS, reduced Co-60-induced oral mucositis through reducing NO production. CONCLUSION: We described a novel model of megavoltage radiation-induced oral mucositis in hamsters. TNF-α, IL-1ß and NO seem to play a role in the pathophysiology of this model.
Assuntos
Citocinas/metabolismo , Óxido Nítrico/metabolismo , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/metabolismo , Estomatite/etiologia , Estomatite/metabolismo , Animais , Radioisótopos de Cobalto/efeitos adversos , Cricetinae , Modelos Animais de Doenças , Guanidinas/farmacologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Mesocricetus , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Pentoxifilina/farmacologia , Peroxidase/metabolismo , Lesões Experimentais por Radiação/imunologia , Radioterapia de Alta Energia/efeitos adversos , Estomatite/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Pentoxifylline (PTX) and thalidomide (TLD) have been shown to inhibit cytokine synthesis, mainly tumor necrosis factor (TNF)-alpha, in different inflammatory conditions. We studied the effects of these cytokine inhibitors in an experimental model of periodontitis. METHODS: Wistar rats were subjected to a ligature placement around the second upper right molars. Alveolar bone loss was evaluated by the sum of the distances between the cusp tip and the alveolar bone along the axis of each molar root, subtracting from the contralateral side. Histopathological analysis was based on cell influx, amount of alveolar bone, and cementum integrity. Animals were weighed daily, and total and differential peripheral white blood cell counts were performed at 6 hours and 1, 7, and 11 days after induction of periodontitis. Groups were treated with saline (positive control), PTX, or TLD 1 hour before and daily up to 11 days after induction of periodontitis. RESULTS: Alveolar bone loss was inhibited 42%, 54%, and 69% by PTX at 5, 15, and 45 mg/kg, and 25%, 25%, 42%, and 54% by TLD at 5, 15, 45, and 90 mg/kg, respectively, as compared to the control (P < 0.05; analysis of variance). Histological analysis showed that PTX and TLD reduced cell influx and alveolar bone and cementum destruction. PTX and TLD also reversed peripheral lymphomonocytosis but not weight loss, as compared to controls. These data showed that both PTX and TLD reduced alveolar bone loss in periodontitis. CONCLUSION: The data showed a protective effect of PTX and TLD on experimental periodontitis, suggesting a role for TNF-alpha in the pathophysiology of periodontitis.
Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Pentoxifilina/uso terapêutico , Periodontite/tratamento farmacológico , Talidomida/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Análise de Variância , Animais , Ligadura , Masculino , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
BACKGROUND: Periodontitis is a chronic disease characterized by alveolar bone loss and inflammatory changes. We studied the effect of disodium chlodronate (CD), a bisphosphonate used in metastatic and metabolic bone disease as a bone resorbing drug, in an experimental periodontitis model (EPD) focusing on anti-resorptive and anti-inflammatory parameters. METHODS: A nylon thread ligature was placed around the left maxillary molars of 72 male Wistar rats who were sacrificed after 7 or 11 days. Groups were treated daily with CD (1, 5, or 25 mg/kg/sc) starting at day 0 until day 7 (prophylactic CD) or from day 5 until day 11 (curative CD) after periodontitis induction. Non-treated group (NT) consisted of rats subjected to periodontitis that received no pharmacological treatment. Alveolar bone loss (ABL) was measured as the distance between the cuspid tips and the alveolar bone. The right jaw was used as control. The hemiarcades were processed for histopathologic analysis. RESULTS: In NT group there was significant ABL, severe mononuclear cells influx, and increase in osteoclast numbers. Prophylactic CD treatment decreased the ABL 25.8%, 61.6%, and 75.5% as compared to NT for the 1, 5, and 25 mg/kg CD doses, respectively. Curative CD treatment decreased the ABL 20%, 62%, and 69% as compared to NT for the 1, 5 and 25 mg/kg CD doses, respectively. Both prophylactic and curative CD decreased histological changes, as compared to NT rats (P <0.01). CONCLUSIONS: CD has both bone sparing and anti-inflammatory activity in EPD in rats when administered as a pretreatment or in an ongoing process. The possibility of using CD as an alternative treatment in human periodontitis should be considered.
Assuntos
Perda do Osso Alveolar/prevenção & controle , Ácido Clodrônico/uso terapêutico , Periodontite/tratamento farmacológico , Análise de Variância , Animais , Masculino , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
The accelerated aging of the Brazilian population will certainly increase the number of institutionalized elderly. Based on this focus, this descriptive and exploratory study was carried out at three asylum institutions in Natal (RN), Brazil, with a view to characterizing the elderly living there, as well as identifying the socioeconomic and health problems and causes that took them to the asylum. The sample consisted of 30% of the total number of elderly in each asylum. These are philanthropic institutions and give shelter to poor elderly persons. Results showed that the three institutions' socioeconomic and health characteristics were similar to what is found in literature, with few financial conditions, family contact marked by conflict, lack or absence of leisure activities, precarious health, restricted medical and nursing care and absence of private health plans. Our reflections on the socioeconomic and health conditions of these persons led to the conclusion that public bodies need to take actions to safeguard their civil rights.