RESUMO
Objective: Chemotherapy treatment against cancer produce systemic toxicities, among which are those related to important structures of the stomatognathic system and its functional activity. 5 Fluorouracil (5-FU) and cyclophosphamide (Cf) are drugs widely used in solid tumors and in bone marrow transplantation, respectively. The objective of this work was to evaluate the toxicity of these drugs regarding functional activity of the submandibular glands, by measuring the percentage of glycogen consumption in two experimental models. Material and Methods: 84 male Wistar rats aged three months were used, housed in individual cages, with controlled temperature and lighting and ad libitum diet. They were divided into four experimental groups: 1) Control (C); 2) Treated with 5-FU+leucovorin (LV) at 20 and 10mg/Kg of body weight respectively for five consecutive days; 3) treated with Cf i.p. at 50mg/Kg of body weight for two consecutive days; and 4) rats with paired feeding (PF): for five and two days respectively, the amount administered resulted from the average of the ingested food of groups 2 and 3. Both submandibular glands were excised. The submandibular glycogen concentration was analyzed at initial time (t0) and after 60 minutes of mechanical stimulation (t60). Results: the average variation changed significantly between time 0 and 60 in the groups C and PF. (p-value=0.0001), the 5-FU + LV treatment group had an average concentration higher at t0 than groups C and PF, without significant consumption at T60. While group Cf showed a lower average concentration at time 0 with respect to groups C and PF, without significant consumption at T60. Conclusion: 5-FU+LV and Cf affect the metabolism of carbohydrates, decreasing the use of glycogen as a metabolic substrate. In the present experimental model, the toxicity of these drugs affected the functional activity of the submandibular gland.
Objetivo: el tratamiento de quimioterapia contra el cáncer produce toxicidades sistémicas, entre las que se encuentran las relacionadas con estructuras importantes del sistema estomatognático y su actividad funcional. El 5-fluorouracilo (5-FU) y la ciclofosfamida (Cf ) son fármacos ampliamente utilizados en tumores sólidos y en trasplantes de médula ósea, respectivamente. El objetivo de este trabajo fue evaluar la toxicidad de estos fármacos con respecto a la actividad funcional de las glándulas submandibulares, midiendo el porcentaje de consumo de glucógeno en dos modelos experimentales. Material y Métodos: se utilizaron 84 ratas Wistar machos de tres meses de edad, alojadas en jaulas individuales, con temperatura e iluminación controladas y dieta ad libitum. Se dividieron en cuatro grupos experimentales: 1) Control (C); 2) Tratados con 5-FU+leucovorina (LV) a 20 y 10mg/Kg de peso corporal, respectivamente, durante cinco días consecutivos; 3) tratados con Cf i.p. a 50mg/Kg de peso corporal durante dos días consecutivos; y 4) ratas con alimentación por parejas (PF): durante cinco y dos días respectivamente, la cantidad administrada resultó del promedio de los alimentos ingeridos de los grupos 2 y 3. Ambas glándulas submandibulares fueron extirpadas. La concentración de glucógeno submandibular se analizó en el momento inicial (t0) y después de 60 minutos de estimulación mecánica (t60). Resultados: la variación promedio cambió significativamente entre el tiempo 0 y 60 en los grupos C y PF. (p=0,0001), el grupo de tratamiento 5-FU+LV tuvo una concentración promedio más alta en t0 que los grupos C y PF, sin un consumo significativo en T60. Mientras que el grupo Cf mostró una concentración promedio más baja en el tiempo 0 con respecto a los grupos C y PF, sin un consumo significativo en T60. Conclusión: 5-FU + LV y Cf afectan el metabolismo de los carbohidratos, disminuyendo el uso de glucógeno como sustrato metabólico. En el presente modelo experimental, la toxicidad de estos medicamentos afectó la actividad funcional de la glándula submandibular.
Assuntos
Animais , Ratos , Glândula Submandibular/fisiologia , Ciclofosfamida/efeitos adversos , Fluoruracila/efeitos adversos , Glicogênio/metabolismo , Ratos Wistar , Ciclofosfamida/uso terapêutico , Fluoruracila/uso terapêutico , AntineoplásicosRESUMO
OBJECTIVE: We have recently reported that experimental periodontitis (EP) reduced methacholine-induced submandibular gland (SMG) salivary secretion. The aim of the present study was to determine whether histamine could prevent SMG impairment produced by EP. MATERIALS AND METHODS: Bilateral EP was induced for 2 weeks and histamine treatment (0.1 mg/kg subcutaneously) was started 5 days before the end of the experimental period in male rats. The histamine effects on periodontitis-altered functional and histological parameters of SMG and on periodontal bone loss were evaluated. RESULTS: Histamine treatment partially reversed the methacholine-induced salivation reduction produced by EP while preventing SMG histological damage. Histamine's effect on SMG was associated with an increased proliferation rate (2.2 ± 0.3 vs. 0.2 ± 0.2 proliferative cells per field, P < 0.001). Furthermore, histamine completely prevented enhanced EP-induced apoptosis (1.0 ± 0.4 vs. 60.9 ± 4.6 apoptotic cells per field, P < 0.001). The protective effect exerted by histamine on SMG functionality is associated with attenuation of lingual and vestibular bone loss (0.66 ± 0.04 vs. 0.97 ± 0.06 mm; P < 0.001). CONCLUSIONS: Histamine is able to reduce periodontitis-induced damage to SMG and bone structure.
Assuntos
Histamina/uso terapêutico , Periodontite/tratamento farmacológico , Salivação/efeitos dos fármacos , Glândula Submandibular/efeitos dos fármacos , Perda do Osso Alveolar/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Histamina/farmacologia , Masculino , Doenças Periodontais , Periodontite/patologia , Periodontite/fisiopatologia , Ratos , Glândula Submandibular/patologia , Glândula Submandibular/fisiologiaRESUMO
BACKGROUND: The incidence of dry mouth and its public health impact are increasing as the result of a progressively larger, medicated older population and because chronic diseases, like periodontitis, are prevalent pathologies among elderly patients. Periodontitis and continuous remodeling and rebuilding alveolar processes greatly affect the margin of the alveolar bone, and there is evidence indicating the role of submandibular glands in the regulation of immune/inflammatory reactions. The purpose of this study was to assess the effect of submandibular-sublingual complex ablation (Sx) on alveolar bone loss in rats submitted or not to ligature-induced experimental periodontal disease (EP). METHODS: Wistar male rats were submitted to Sx or sham operations (day 0). Two weeks later, unilateral EP was induced on the right mandibular first molars for 7 days with the contralateral side serving as control. Bone loss at the level of the dental pieces was estimated by bone histomorphometry on mesio-distally oriented sections of the molars and by the determination on lingual and vestibular mandibular surfaces of the distances from the cemento-enamel junction to the alveolar crest. RESULTS: Sx and EP significantly increased lingual and vestibular alveolar bone loss. Molars with EP exhibited greater lingual loss in Sx animals compared to those with the sham operation. EP induced similar interradicular bone loss in sham and Sx rats. CONCLUSION: Sx has a deleterious effect on the periodontal tissues, particularly marginal alveolar bone, indicating the importance of the submandibular/sublingual glands in maintaining healthy periodontal conditions.
Assuntos
Perda do Osso Alveolar/etiologia , Periodontite/complicações , Saliva/fisiologia , Glândula Submandibular/fisiologia , Perda do Osso Alveolar/patologia , Animais , Ligadura , Masculino , Doenças Mandibulares/etiologia , Doenças Mandibulares/patologia , Ratos , Ratos Wistar , Glândula Sublingual/fisiologia , Glândula Sublingual/cirurgia , Glândula Submandibular/cirurgiaRESUMO
We previously reported that intravenously administered atrial natriuretic factor (ANF) induced no salivation but enhanced agonist-evoked secretion in submandibular glands. The gene expression of ANF and natriuretic peptide receptors (NPR) was later reported in the glands. In the present study we sought to establish the intracellular signalling mechanisms underlying ANF modulation of salivary secretion. Fasted rats were prepared with submandibular duct and femoral cannulation. Dose-response curves to methacholine (MC) and norepinephrine (NE) were performed in the presence of cANP (4-23 amide) (selective NPR-C agonist) and ANF. Local injection of the agonist or ANF-induced no salivation, but enhanced MC and NE-evoked secretion. ANF and cANP (4-23 amide) enhanced phosphoinositide turnover being the effect abolished by U73122 (PLC inhibitor). Further ANF and cANP (4-23 amide) decreased basal cAMP content but failed to affect isoproterenol or forskolin-evoked cAMP. ANF response was inhibited by pertussis toxin and mimicked by cANP (4-23 amide) strongly supporting NPR-C activation. ANF-induced cAMP reduction was abolished by PLC and PKC inhibitors. The content of cGMP was dose dependently stimulated by ANF but not modified by cANP (4-23 amide). These findings support that ANF through NPR-C receptors coupled to PLC activation and adenylyl cyclase inhibition interacts with sialogogic agonists in the submandibular gland to potentiate salivation.
Assuntos
Fator Natriurético Atrial/fisiologia , Transdução de Sinais/efeitos dos fármacos , Glândula Submandibular/fisiologia , Animais , Fator Natriurético Atrial/metabolismo , Fator Natriurético Atrial/farmacologia , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Cloreto de Metacolina/farmacologia , Norepinefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Salivação/efeitos dos fármacos , Glândula Submandibular/metabolismoRESUMO
The rat submandibular gland grows significantly during the first 10 weeks of postnatal life. During this growth, there is differentiation and maturation of the definitive glandular structures, (acini, intercalated ducts, convoluted granular tubules, striated ducts and excretory ducts) within a highly vascularized stroma. In this study, the absolute volume of each glandular component during postnatal development was determined morphometrically. The increases in gland mass and component volumes were analyzed allometrically relative to the growth of body mass, using Walds non-parametric method. The allometric growth of gland mass was monophasic and negative (k<1), with k = 0.86. The absolute volumes of the acini plus terminal tubules, intercalated ducts, striated ducts and excretory ducts all showed a biphasic pattern, with the first phase occuring from day 2 to day 28 and the second phase from day 28 to day 96. In the first phase, all of the structures showed positive allometric growth (k>1), with k values from 1.09, 1.15, 1.49 and 1.17, for the acini plus terminal tubules, intercalated ducts, striated ducts and excretory ducts, respectively, while in the second phase, all showed negative allometrtic growth (k<1), with k values of 0.72, 0.33, 0.77 and 0.82, respectively. The convoluted granular tubules showed a single phase of positive allometric growth (k>1) between 28 and 96 days of age, with k=1.28, whereas the stromal volume showed negative allometric growth (k<1) from day 14 to day 96, with k=0.77.
Assuntos
Animais , Masculino , Ratos , Glândula Submandibular/anatomia & histologia , Glândula Submandibular/crescimento & desenvolvimento , Glândula Submandibular , Glândula Submandibular/fisiologia , Ratos WistarRESUMO
Os autores apresentam as características clínicas e radiográficas de um caso de sialolitíase da glândula salivar submandibular em um paciente do sexo masculino, leucoderma na quinta década de vida. Por meio de uma revisäo de literatura, os autores descrevem os aspectos anatômicos, fisiológicos e patológicos relacionados com as alteraçäes encontratadas. concluem que o tratamento pode ser fisioterápico ou cirúrgico, embora para o caso relatado em questäo, o tratamento eleito foi o cirúrgico em virtude do tamanho do sialolito encontrado.(au)
Assuntos
Humanos , Masculino , Adulto , Cálculos dos Ductos Salivares/diagnóstico , Glândula Submandibular/anatomia & histologia , Glândula Submandibular/fisiologia , Glândula Submandibular/patologiaRESUMO
BACKGROUND: Histamine is released from mast cells by immunologic and non-immunologic stimuli during salivary gland inflammation, regulating salivary secretion. The receptor-secretory mechanism has not been studied in detail. AIMS: The studies reported were directed toward elucidating signal transduction/second messenger pathways within the rat submandibular gland associated with 2-thiazolylethylamine (ThEA)-induced H(1)-receptor responses. MATERIALS AND METHODS: To assess the H(1) receptor subtype expression in the rat submandibular gland, a radioligand binding assay was performed. The study also included inositolphosphates and cyclic GMP accumulation, protein kinase C and nitric oxide synthase activities, and amylase release. RESULTS: The histamine H(1) receptor subtype is expressed on the rat submandibular gland with high-affinity binding sites. The ThEA effect was associated with activation of phosphoinositide-specific phospholipase C, translocation of protein kinase C, stimulation of nitric oxide synthase activity and increased production of cyclic GMP. ThEA stimulation of nitric oxide synthase and cyclic GMP was blunted by agents able to interfere with calcium movilization, while a protein kinase C inhibitor was able to stimulate ThEA action. On the other hand, ThEA stimulation evoked amylase release via the H1 receptor but was not followed by the L-arginine/nitric oxide pathway activation. CONCLUSIONS: These results suggest that, apart from the effect of ThEA on amylase release, it also appears to be a vasoactive chemical mediator that triggers vasodilatation, modulating the course of inflammation.
Assuntos
Óxido Nítrico/fisiologia , Receptores Histamínicos H1/fisiologia , Transdução de Sinais/fisiologia , Glândula Submandibular/fisiologia , Amilases/metabolismo , Animais , GMP Cíclico/metabolismo , Agonistas dos Receptores Histamínicos/farmacologia , Técnicas In Vitro , Óxido Nítrico Sintase/metabolismo , Fosfatidilinositóis/metabolismo , Ratos , Glândula Submandibular/efeitos dos fármacos , Tiazóis/farmacologia , Fosfolipases Tipo C/metabolismoRESUMO
Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important in the regulation of the function of different organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in submandibular glands (SMG) and blocked stimulated salivary secretion in adult male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. Furthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in PGE and the production of NO. The incubation of slices of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly significantly. The incubation of SMG in the presence of a PGE(1) analog (alprostadil) increased the production of NO. These results indicate that LPS activates NOS, leading to NO release, which activates COX, generating PGEs that act back to further activate NOS, causing further generation of PGEs by activation of COX. Because the alprostadil administration inhibited stimulated salivation, LPS-induced inhibition of salivation appears to be caused by increased PGE production. Diminished salivary secretion produces poor oral health; thus the use of COX-2 inhibitors to counteract the effects of inhibited salivation should be considered.
Assuntos
Lipopolissacarídeos/administração & dosagem , Prostaglandinas E/metabolismo , Saliva/metabolismo , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/fisiologia , Alprostadil/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Ácido Araquidônico/metabolismo , Fármacos do Sistema Nervoso Autônomo/farmacologia , Ciclo-Oxigenase 2 , Inibidores Enzimáticos/farmacologia , Guanidinas/farmacologia , Técnicas In Vitro , Injeções Intraperitoneais , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Masculino , Meloxicam , Cloreto de Metacolina/farmacologia , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Norepinefrina/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Tiazinas/farmacologia , Tiazóis/farmacologiaRESUMO
IFN gamma is a pleiotropic cytokine that exerts immunologic and non-immunologic functions. We show here that at low doses (10 U/ml), it stimulates amylase secretion in murine submandibular glands (SMG) "via" muscarinic receptor activation, comparable to that produced by the muscarinic agonist carbachol. Both effects are blocked by atropine. NG-monomethyl-L-arginine (L-NMMA) and EGTA inhibited the cytokine effect on amylase secretion, involving the participation of a calcium-dependent isoform of nitric oxide synthase (NOS). We confirm NOS activation because IFN gamma stimulates nitrite production and enzyme activity in SMG. Carbachol (10(-7) M) did not modify basal nitric oxide production. In addition, both IFN gamma and carbachol increase prostaglandin E2 production in SMG, but while indomethacin potentiates IFN gamma effect on amylase secretion, it blunted amylase secretion exerted by carbachol. Thus, IFN gamma and carbachol stimulate IFN gamma secretion on SMG in a dose-dependent manner. Our results are pointing to neuroregulatory functions of IFN gamma in murine SMG, because it regulates its own levels in oral cavity, perhaps to exert a local immuno-surveillance.
Assuntos
Amilases/metabolismo , Interferon gama/farmacologia , Sistema Nervoso Parassimpático/efeitos dos fármacos , Sistema Nervoso Parassimpático/fisiologia , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/fisiologia , Animais , Carbacol/farmacologia , Dinoprostona/biossíntese , Ácido Egtázico/farmacologia , Feminino , Interferon gama/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/metabolismo , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/fisiologia , Proteínas Recombinantes , Glândula Submandibular/imunologia , Glândula Submandibular/inervação , ômega-N-Metilarginina/farmacologiaRESUMO
Saliva secretion during feeding facilitates chewing, swallowing and other oral functions. Between meals, a "resting saliva" is elicited to allow speaking and contribute to maintain soft and hard tissues health. Chewing is the main stimulus for "stimulated saliva" secretion. Mouth dryness and other less well known stimuli control "resting saliva". In humans the stimulus of the light increases the parotid saliva flow rate. Saliva secretion occurs in response to a reflex. Both motor branches of the autonomous nervous system drive efferent outputs to the salivary glands. Cellular bodies of sympathetic motor fibers innervating salivary glands are located in the superior cervical ganglia. A multisynaptic pathway couples the superior cervical ganglia to hypothalamic areas related to the control of autonomous and endocrine functions. Projections from suprachiasmatic nuclei involved in circadian rhythms control reach those areas. Salivary glands postsynaptic beta-adrenoceptors control synthesis and secretion of proteins. Postsynaptic alpha 2-adrenoceptors modulate salivary responses mediated by alpha 1 and beta-adrenoceptors. Parotid alpha-amylase circadian rhythm in suckling rats, suggest that the sympathetic nervous system mediates an effect of light on saliva secretion. Analysis of: 1) parotid fine structure, 2) submandibular secretory response to adrenergic agonists, and 3) submandibular 3H-clonidine binding to alpha 2-adrenoceptors, demonstrated that an increase of sympathetic reflex activity occurs in salivary glands of rats chronically exposed to constant light. Similar effects were observed in rats chronically exposed to immobilization stress. Catecholamine biosynthetic enzyme mRNA levels in adrenal glands and superior cervical ganglia suggest that changes induced by light on salivary sympathetic reflex activity are mediated by plasma catecholamines released by adrenal glands. Post and presynaptic alpha 2 adrenoceptors could play an important role in saliva secretion control when light or stress stimuli modify the sympathoadrenal system.