RESUMO
BACKGROUND/AIM: The purpose of this study was to determine the anti-aging effects of coffee intake on oxidative stress in rat periodontal tissue and alveolar bone loss. MATERIALS AND METHODS: Male Fischer 344 rats (8 weeks old) were randomized to four groups; the baseline group immediately sacrificed, the control group fed with normal powdered food for 8 weeks, and the experimental groups fed with powdered food containing 0.62% or 1.36% coffee components for 8 weeks. RESULTS: Alveolar bone loss and gingival level of 8-hydroxydeoxyguanosine were significantly lower in the 1.36% coffee group than in the control group. Nuclear factor erythroid 2-related factor 2 translocation to the nucleus was significantly higher in the 1.36% coffee group than in the control group. CONCLUSION: Continuous intake of 1.36% coffee could prevent age-related oxidative stress in the periodontal tissue and alveolar bone loss, possibly by up-regulating the Nrf2 signaling pathway.
Assuntos
Envelhecimento/metabolismo , Café , Ingestão de Líquidos , Estresse Oxidativo/efeitos dos fármacos , Periodonto/efeitos dos fármacos , Periodonto/metabolismo , Animais , Antioxidantes/farmacologia , Biomarcadores , Imuno-Histoquímica , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , RatosRESUMO
OBJECTIVE: The purpose of this study was to investigate the preventive effects of topical application of green tea catechins on tongue oxidative stress induced by 5-fluorouracil (5-FU) administration in rats. DESIGN: Male Wistar rats (n=28, 8 weeks old) were divided into four groups of seven rats each: a negative control group (saline administration and application of ointment without green tea catechins), a positive control group (5-FU administration and application of ointment without green tea catechins), and two experimental groups (5-FU administration and application of ointment containing 0.1% or 0.5% green tea catechins). Topical application of each ointment to the ventral surface of the tongue was performed once a day for 5days. The level of 8-hydroxydeoxyguanosine (8-OHdG) was determined to evaluate oxidative stress. Fluorescence staining was also performed to confirm nuclear factor erythroid 2-related factor 2 (Nrf2) translocation to the nucleus. RESULTS: After the experimental period, the ratios of 8-OHdG-positive cells in the ventral tongue tissue were higher in the positive control group than in the negative control group (P<0.05). On the other hand, those in the 0.5% green tea catechin group, but not in the 0.1% green tea catechin group, were lower than the positive control group (P<0.05). In addition, Nrf2 translocation to the nucleus was greater in the 0.5% green tea catechin group than in the positive control group (P<0.05). CONCLUSIONS: Topical application of ointment containing 0.5% green tea catechins could prevent tongue oxidative stress in 5-FU administered rats, via up-regulation of the Nrf2 signaling pathway.
Assuntos
Catequina/farmacologia , Fluoruracila/toxicidade , Pomadas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Chá , Língua/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina , Administração Tópica , Animais , Antioxidantes/metabolismo , Catequina/administração & dosagem , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Pomadas/administração & dosagem , Ratos , Ratos WistarRESUMO
This cross-sectional study addressed the relationship between coffee consumption and periodontitis in patients during the maintenance phase of periodontal treatment. A total of 414 periodontitis patients in the maintenance phase of periodontal treatment completed a questionnaire including items related to coffee intake and underwent periodontal examination. Logistic regression analysis showed that presence of moderate/severe periodontitis was correlated with presence of hypertension (Odds Ratio (OR) = 1.99, p < 0.05), smoking (former, OR = 5.63, p < 0.01; current, OR = 6.81, p = 0.076), number of teeth present (OR = 0.89, p < 0.001), plaque control record ≥20% (OR = 1.88, p < 0.05), and duration of maintenance phase (OR = 1.07, p < 0.01). On the other hand, presence of severe periodontitis was correlated with smoking (former, OR = 1.35, p = 0.501; current, OR = 3.98, p < 0.05), coffee consumption (≥1 cup/day, OR = 0.55, p < 0.05), number of teeth present (OR = 0.95, p < 0.05), and bleeding on probing ≥ 20% (OR = 3.67, p < 0.001). There appears to be an inverse association between coffee consumption (≥1 cup/day) and prevalence of severe periodontitis in the maintenance phase of periodontal treatment.
Assuntos
Café , Periodontite/epidemiologia , Periodontite/terapia , Adulto , Idoso , Doença Crônica , Estudos Transversais , Placa Dentária/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Periodontite/fisiopatologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Fumar/epidemiologia , Inquéritos e Questionários , DenteRESUMO
To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl ω-chain moiety of the γ-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented.
Assuntos
Lactamas/síntese química , Lactamas/farmacologia , Prostaglandinas E Sintéticas/síntese química , Prostaglandinas E Sintéticas/farmacologia , Receptores de Prostaglandina E Subtipo EP2/agonistas , Receptores de Prostaglandina E Subtipo EP4/agonistas , Administração Tópica , Animais , Pressão Sanguínea/efeitos dos fármacos , Células CHO , Cricetinae , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Dinoprostona/química , Avaliação Pré-Clínica de Medicamentos/métodos , Consolidação da Fratura/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Lactamas/administração & dosagem , Masculino , Camundongos , Microesferas , Estrutura Molecular , Poliglactina 910/administração & dosagem , Poliglactina 910/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Tiazolidinas/químicaRESUMO
Abdominal aortic aneurysm (AAA) pathogenesis is distinguished by vessel wall inflammation. Cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1, key components of the most well-characterized inflammatory prostaglandin pathway, contribute to AAA development in the 28-day angiotensin II infusion model in mice. In this study, we used this model to examine the role of the prostaglandin E receptor subtype 4 (EP4) and genetic knockdown of COX-2 expression (70% to 90%) in AAA pathogenesis. The administration of the prostaglandin receptor EP4 antagonist AE3-208 (10 mg/kg per day) to apolipoprotein E (apoE)-deficient mice led to active drug plasma concentrations and reduced AAA incidence and severity compared with control apoE-deficient mice (P < 0.01), whereas COX-2 genetic knockdown/apoE-deficient mice displayed only a minor, nonsignificant decrease in incidence of AAA. EP4 receptor protein was present in human and mouse AAA, as observed by using Western blot analysis. Aortas from AE3-208-treated mice displayed evidence of a reduced inflammatory phenotype compared with controls. Atherosclerotic lesion size at the aortic root was similar between all groups. In conclusion, the prostaglandin E(2)-EP4 signaling pathway plays a role in the AAA inflammatory process. Blocking the EP4 receptor pharmacologically reduces both the incidence and severity of AAA in the angiotensin II mouse model, potentially via attenuation of cytokine/chemokine synthesis and the reduction of matrix metalloproteinase activities.
Assuntos
Aneurisma da Aorta Abdominal/fisiopatologia , Receptores de Prostaglandina E Subtipo EP4/fisiologia , Adulto , Angiotensina II , Animais , Aorta/metabolismo , Aorta/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/prevenção & controle , Ruptura Aórtica/prevenção & controle , Aterosclerose/patologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Naftalenos/farmacologia , Naftalenos/uso terapêutico , Fenilbutiratos/farmacologia , Fenilbutiratos/uso terapêutico , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Receptores de Prostaglandina E Subtipo EP4/deficiência , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Transdução de Sinais/fisiologia , UltrassonografiaRESUMO
To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of γ-lactam prostaglandin E analogs bearing a 16-phenyl ω-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration.
Assuntos
Prostaglandinas Sintéticas/química , Receptores de Prostaglandina E Subtipo EP2/agonistas , Receptores de Prostaglandina E Subtipo EP4/agonistas , Tiazolidinas/química , Administração Tópica , Animais , Células CHO , Cricetinae , Cricetulus , Avaliação Pré-Clínica de Medicamentos , Fraturas Ósseas/tratamento farmacológico , Isomerismo , Camundongos , Prostaglandinas Sintéticas/síntese química , Prostaglandinas Sintéticas/uso terapêutico , Ratos , Receptores de Prostaglandina E Subtipo EP2/genética , Receptores de Prostaglandina E Subtipo EP2/metabolismo , Receptores de Prostaglandina E Subtipo EP4/genética , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Relação Estrutura-Atividade , Tiazolidinas/síntese química , Tiazolidinas/uso terapêuticoRESUMO
OBJECTIVE: this study examined the effects of a dentifrice containing green tea catechins on gingival oxidative stress and periodontal inflammation using a rat model. DESIGN: twenty-four male Wister rats were randomly divided into four groups. The first group (Control group) received no treatment for 8 weeks. Periodontal inflammation was induced in the second group for 8 weeks. Periodontal inflammation was induced in the last two groups for 8 weeks and dentifrices with or without green tea catechins were topically applied to the gingival sulcus daily for 4 weeks prior to the end of the experimental period. RESULTS: rats that had experimental periodontal inflammation showed apical migration of the junctional epithelium, alveolar bone loss and inflammatory cell infiltration in the connective tissue subjacent to the junctional epithelium at 8 weeks, whilst the control group showed no pathologic changes. Topical application of a green tea catechin-containing dentifrice reduced inflammatory cell infiltration in the periodontal lesions to a greater degree than the control dentifrice at 8 weeks. The gingiva in which green tea catechin-containing dentifrice was applied also showed a lower level of expression of hexanoyl-lysine (a marker of lipid peroxidation), nitrotyrosine (a marker of oxidative protein damage), and tumour necrosis factor-α (an indicator of pro-inflammatory cytokines) at 8 weeks compared to gingiva in which the control dentifrice was applied. CONCLUSIONS: adding green tea catechins to a dentifrice may contribute to prevention of periodontal inflammation by decreasing gingival oxidative stress and expression of pro-inflammatory cytokines.
Assuntos
Antioxidantes/uso terapêutico , Camellia sinensis , Catequina/uso terapêutico , Dentifrícios/uso terapêutico , Gengiva/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Periodontite/prevenção & controle , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/prevenção & controle , Animais , Catequina/análogos & derivados , Tecido Conjuntivo/efeitos dos fármacos , Tecido Conjuntivo/patologia , Modelos Animais de Doenças , Inserção Epitelial/efeitos dos fármacos , Inserção Epitelial/patologia , Gengiva/patologia , Retração Gengival/patologia , Retração Gengival/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , Lisina/análise , Lisina/efeitos dos fármacos , Masculino , NF-kappa B/análise , NF-kappa B/efeitos dos fármacos , Periodontite/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Tirosina/análogos & derivados , Tirosina/análise , Tirosina/efeitos dos fármacosRESUMO
Activating mutations of K-ras are frequent in colon tumors and aberrant crypt foci, and may play important roles in colon carcinogenesis. Here, we investigated the effects of a K-ras codon 12 mutation on inducible nitric oxide synthase (iNOS) expression. When rat intestinal epithelial cells (IEC-6) were transfected with K-rasAsp12 cDNA, the iNOS expression linked to interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS) treatment was markedly increased and prolonged. In contrast, it was only very faint and transient in cells transfected with the control vector or K-rasWT. Electrophoretic mobility-shift assays demonstrated that NF-kappaB binding activity induced by IL-1beta or LPS was also increased in K-rasAsp12-transfected cells, along with the binding of CREB-1, CREM-1, ATF-1, ATF-2, and Jun D to a cAMP-responsive element (CRE)-like site and the binding of C/EBPbeta to a C/EBP-binding consensus site. Furthermore, the anchorage-independent growth of K-rasAsp12-transfected cells was markedly increased by IL-1beta or LPS treatment, and decreased by ONO-1714, an iNOS inhibitor. In addition, tumor growth in nude mice injected with K-rasAsp12-transfected cells was significantly suppressed by NOS inhibition with 50 p.p.m. ONO-1714 or 100 p.p.m. L-NG-nitroarginine methyl ester. These results suggest that an activating mutation of K-ras can markedly enhance the iNOS expression mediated by IL-1beta or LPS, through the activation of promoters on NF-kappaB, C/EBP, and CRE-like sites, and that nitric oxide contributes to the colony formation and tumor growth of K-ras-transformed cells.