RESUMEN
To evaluate the effect of high-graduation chronic ethanol (EtOH) intake on bone and periodontal tissues of rats. Male Wistar rats (250 g) were divided into two groups of n = 12 each one. EtOH (5 ml of 3 g/kg) was administered to the experimental group by gastric gavage twice a day for 20 days and the control group received water under the same conditions. The rats were euthanized and used to perform biochemical determination in plasma and gingival tissue, and histological and biomechanical studies in the femur and mandibular tissues. Alcohol increased both TNFα (p < 0.01) and PGE2 (p < 0.05) in plasma and gingiva (p < 0.05) as compared to controls. In addition, EtOH increased the alveolar bone loss as evidenced by the increased distance between the cement enamel junction and the alveolar crest (p < 0.01), the lower % of interradicular bone expressed as bone area/total area (B.Ar/T.Ar, p < 0.05) and the larger periodontal space (p < 0.05), as compared to controls. Likewise, the mandibular microtomographic analysis in alcoholized rats revealed a lower % of interradicular bone volume/total volume (BV/TV, p < 0.05), greater trabecular separation (p < 0.05) and greater % trabecular porosity (p < 0.05) than controls. No biomechanical alteration was observed in lower jaws, while the femur of alcoholized rats presented a decrease in the structural bone properties (p < 0.001), as a systemic consequence of deterioration of the diaphyseal architecture (p < 0.01) without changes in material properties. The consumption of high doses of alcohol produces deleterious effects on periodontal tissues that could be due not only to local but also systemic effects.
Asunto(s)
Pérdida de Hueso Alveolar , Etanol , Fémur , Ratas Wistar , Animales , Masculino , Ratas , Etanol/farmacología , Fenómenos Biomecánicos , Fémur/efectos de los fármacos , Microtomografía por Rayos X , Mandíbula , Factor de Necrosis Tumoral alfa/sangre , Encía/efectos de los fármacos , Dinoprostona , Consumo de Bebidas AlcohólicasRESUMEN
The aim was to characterise the endocannabinoid system (ECS) in the dental pulp of teeth at different stages of eruption. Pulp of: erupted premolars (EPM), third molars in pre-eruptive (PThM), intraosseous (IThM) and eruptive stages (EThM) (n = 12 each group) were used. Messenger RNA expression of components of the ECS as cannabinoid receptors (CBr1 and CBr2), and anandamide synthetizing (NAPE-PLD) and degradation (FAAH) enzymes were measured by RT-PCR. Data were analysed using Student's t-test for comparisons between two groups and one-way analysis of variance and Tukey's post-test for multiple comparisons (statistical significance: p < 0.05). mRNA expression of CBr2, NAPE-PLD and FAAH was similar in the studied stages, was lower in IThM than in PThM and EThM, and the lowest in EThM (p < 0.01); of note, CBr2 mRNA expression was not detected in EThM. CBr1 mRNA did not differ significantly between IThM and PThM but was lower in EThM (p < 0.01). The absence of CBr2 and presence of CBr1 in EThM suggest the involvement of the ECS via CBr1 as a mediator of tooth and bone tissue homeostasis during tooth eruption.
Asunto(s)
Endocannabinoides , Anomalías Dentarias , Humanos , Endocannabinoides/metabolismo , Erupción Dental , Huesos/metabolismo , Receptores de Cannabinoides , ARN Mensajero/metabolismoRESUMEN
El apiñamiento dental es una maloclusión frecuen-te y junto con los requerimientos de estética dental son una causa habitual de la solicitud de tratamien-to ortodóncico. El tiempo que demanda y las moles-tias que pudiera ocasionar el tratamiento produce inquietud en los pacientes y un esfuerzo de los or-todoncistas para optimizar el tiempo y prevenir los efectos adversos. Los tratamientos odontológicos multidisciplinarios permiten una mejor respuesta estética, funcional y de estabilidad post tratamiento. El tiempo de alineación dentaria y finalización, en los pacientes tratados con láser de baja intensidad po-dría mejorar tanto los índices gingivales como la res-puesta al dolor. Adicionalmente, las corticales óseas de los pacientes con ortodoncia tratados con láser, podrían verse menos afectadas en comparación con las de los pacientes no tratados. Se presenta un caso de fotobioestimulación con láser de baja intensidad aplicado en un paciente en fase de alineación, que forma parte de un estudio prospectivo aleatorizado que se desarrolla en la FOUBA y fue aprobado por el comité de Ética de la institución. El paciente aceptó y firmó el consentimiento informado. Finalizada la etapa de alineación, se evaluó la efectividad de la te-rapia con láser de baja intensidad actualmente de-nominada fotobiomodulación en incisivos superiores en la fase de alineación para acelerar el movimiento dentario, la respuesta gingival, el dolor, el estado de la cortical alveolar vestibular y la estética del perfil (AU)
Dental crowding, which is a frequent malocclusion, and dental aesthetic requirements are a common cause for requesting orthodontic treatment. The time that the treatment requires and the inconvenience that it could cause worries the patient and makes orthodontists strive to optimize time and prevent adverse effects. Multidisciplinary treatments would allow a better aesthetic, functional and post-treatment stability response. The dental alignment and completion time in patients treated with low-intensity laser could improve both gingival indices and response to pain. Additionally, the bone cortical of orthodontic patients treated with laser could be less affected compared to those of untreated patients. A case of low-intensity laser photobiostimulation applied to a patient in the alignment phase is presented, which is part of a prospective randomized study carried out at FOUBA and was approved by the institution's Ethics Committee. The patient accepted and signed the informed consent. After the alignment phase, the effectiveness of low-level laser therapy actually called photobiomodulation in upper incisors in the alignment phase is evaluated to accelerate tooth movement; the gingival response; the pain; the vestibular alveolar cortical and the aesthetics of the profile (AU)
Asunto(s)
Humanos , Masculino , Adolescente , Fototerapia/métodos , Técnicas de Movimiento Dental , Terapia por Luz de Baja Intensidad/métodos , Ortodoncia Correctiva , Planificación de Atención al Paciente , Índice Periodontal , Soportes Ortodóncicos , Tomografía Computarizada de Haz Cónico Espiral/métodosRESUMEN
Recent findings relate obesity to inflammation in key hypothalamic areas for body weight control. Hypothalamic inflammation has also been related to oxidative stress. Palmitic acid (PA) is the most abundant free fatty acid found in food, and in vitro studies indicate that it triggers a pro-inflammatory response in the brain. Melanocortins are neuropeptides with proven anti-inflammatory and neuroprotective action mediated by melanocortin receptor 4 (MC4R), but little is known about the effect of melanocortins on oxidative stress. The aim of this study was to investigate whether melanocortins could alleviate oxidative stress induced by a high fat diet (HFD) model. We found that NDP-MSH treatment decreased PA-induced reactive oxygen species production in astrocytes, an effect blocked by the MC4R inhibitor JKC363. NDP-MSH abolished nuclear translocation of Nrf2 induced by PA and blocked the inhibitory effect of PA on superoxide dismutase (SOD) activity and glutathione levels while it also per se increased activity of SOD and γ-glutamate cysteine ligase (γ-GCL) antioxidant enzymes. However, HFD reduced hypothalamic MC4R and brain derived neurotrophic factor mRNA levels, thereby preventing the neuroprotective mechanism induced by melanocortins.
Asunto(s)
Antiinflamatorios/administración & dosificación , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Encefalitis/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ácido Palmítico/administración & dosificación , alfa-MSH/análogos & derivados , Animales , Dieta Alta en Grasa , Encefalitis/complicaciones , Encefalitis/prevención & control , Masculino , Obesidad/complicaciones , Cultivo Primario de Células , Ratas Endogámicas WKY , Ratas Wistar , Transducción de Señal , alfa-MSH/administración & dosificaciónRESUMEN
Saliva is very important to oral health, and a salivary deficit has been shown to bring serious problems to oral health. There is scant information about the mechanisms through which salivary glands participate in post-tooth extraction socket healing. Therefore, the aim of the present study was to investigate the effect of submandibulectomy (SMx), consisting of the ablation of submandibular and sublingual glands (SMG and SLG, respectively), on PGE2 signaling and other bone regulatory molecules, such as OPG and RANKL, involved in tooth extraction socket healing. Male Wistar rats, 70 g body weight, were assigned to an experimental (subjected to SMx) or a control group (sham operated). One week later, the animals in both groups underwent bilateral extraction of the first mandibular molars. The effect of SMx on different stages of socket healing after tooth extraction (7, 14, and 30 days) was studied by evaluating some parameters of inflammation, including PGE2 and its receptors, and of bone metabolism, as well as by performing bone biomechanical studies. SMx increased TNFα and PGE2 content as well as cyclooxygenase-II (COX-II) expression in tooth socket tissue at almost all the studied time points. SMx also had an effect on mRNA expression of PGE2 receptors at the different time points, but did not significantly alter osteoprotegerin (OPG) and RANKL mRNA expression at any of the studied time points. In addition, an increase in bone mass density was observed in SMx rats compared with matched controls, and the structural and mechanical bone properties of the mandibular socket bone were also affected by SMx. Our results suggest that the SMG/SLG complex regulates cellular activation and differentiation by modulating the production of molecules intervening in tooth extraction socket repair, including the PGE2 signaling system, which would therefore account for the higher density and resistance of the newly formed bone in SMx rat.
Asunto(s)
Inflamación/patología , Prostaglandina-E Sintasas/metabolismo , Receptores de Prostaglandina/metabolismo , Saliva/metabolismo , Conductos Salivales/cirugía , Extracción Dental , Alveolo Dental/patología , Cicatrización de Heridas/fisiología , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND: Anti-inflammatory and immunologic properties of cannabinoids have been reported in several tissues. Expression of cannabinoid receptor Type 2 was reported in osteoblasts and osteoclasts, suggesting a key role in bone metabolism. The aim of this study is to assess the effect of treatment with cannabinoid-2 receptor agonist HU-308 in the oral health of rats subjected to lipopolysaccharide (LPS)-induced periodontitis. METHODS: Twenty-four rats were distributed in four groups (six rats per group): 1) control rats; 2) sham rats; 3) rats submitted to experimental periodontitis (LPS); and 4) rats submitted to experimental periodontitis and treated with HU-308 (LPS+HU). In groups LPS and LPS+HU, periodontitis was induced by LPS (1 mg/mL) injected into the gingival tissue (GT) of maxillary and mandibular first molars and into the interdental space between the first and second molars, 3 days per week for 6 weeks. In group LPS+HU, HU-308 (500 ng/mL) was applied topically to the GT daily. RESULTS: Alveolar bone loss resulting from LPS-induced periodontitis was significantly attenuated with HU-308 treatment (LPS+HU), measured by macroscopic and histologic examination. Treatment also reduced gingival production of inflammatory mediators augmented in LPS-injected rats, such as: 1) inducible nitric oxide (iNOS) activity (LPS: 90.18 ± 36.51 pmol/minute/mg protein versus LPS+HU: 16.37 ± 4.73 pmol/minute/mg protein; P <0.05); 2) tumor necrosis factor alpha (LPS: 185.70 ± 25.63 pg/mg protein versus LPS+HU: 95.89 ± 17.47 pg/mg protein; P <0.05); and 3) prostaglandin E2 (PGE2) (LPS: 159.20 ± 38.70 pg/mg wet weight versus LPS+HU: 71.25 ± 17.75 pg/mg wet weight; P <0.05). Additionally, HU-308 treatment prevented the inhibitory effect of LPS-induced periodontitis on the salivary secretory response to pilocarpine. Moreover, iNOS activity and PGE2 content, which were increased by LPS-induced periodontitis in the submandibular gland, returned to control values after HU-308 treatment. CONCLUSION: This study demonstrates anti-inflammatory, osteoprotective, and prohomeostatic effects of HU-308 in oral tissues of rats with LPS-induced periodontitis.
Asunto(s)
Cannabinoides/farmacología , Periodontitis/dietoterapia , Pérdida de Hueso Alveolar , Animales , Lipopolisacáridos , Ratas , Receptores de CannabinoidesRESUMEN
The aim of the present study was to perform a biochemical, histological, and histomorphometrical evaluation of the mechanisms involved in tissue repair in rats subjected to submandibulectomy-induced hyposialia, 24, 48, and 72 hours of post-tooth extraction. We studied the correlation between the lack of submandibular saliva and the modulation of inflammatory mediators involved in tissue repair, such as prostaglandin E2 , nitric oxide (NO), and tumor necrosis factor alpha (TNF-α). Rats with hyposialia showed a delay in socket healing, slow replacement of the clot with granulation tissue, and fewer cells and collagen fibers, concomitant with a longer inflammatory process, as compared to controls. The lack of saliva induced by submandibulectomy modified the levels of prostaglandin E2 , NO, and TNF-α, and tissue response in the early stages of wound healing compared to controls, and could thus determine alterations in later osteogenic response. Our results allow concluding that hyposialia modulates the parameters of inflammation studied here, and that it is essential for optimal healing. Therefore, these findings provide evidence for the importance of submandibular saliva to final bone socket healing.
Asunto(s)
Tejido de Granulación/patología , Inflamación/patología , Saliva/metabolismo , Alveolo Dental/patología , Cicatrización de Heridas , Xerostomía/patología , Animales , Masculino , Ratas , Ratas Wistar , Saliva/inmunología , Factores de Tiempo , Extracción Dental , Alveolo Dental/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Xerostomía/complicacionesRESUMEN
BACKGROUND: The aim of this study was to assess the effects of chronic alcohol consumption on periodontitis development in rats. METHODS: Periodontal disease was experimentally induced by lipopolysaccharide (LPS; 2 mg/ml) injections into the gingival tissue around first upper and lower molar's neck, and into the interdental space between first and second molars. This protocol was repeated for 6 weeks on days 1, 3, and 5 of each week. Chronic alcohol consumption was induced by 20% ethanol (EtOH) as the only liquid source during 4 months. RESULTS: Chronic alcohol consumption by itself increased alveolar bone loss and biological mediators of periodontal disease such as prostaglandin E2 (PGE2 ) content on gingival tissue, and inducible nitric oxide synthase activity plus PGE2 content in submandibular gland. Unexpectedly, alcohol consumption did not increase the damage evoked by the proved model of LPS injections for periodontitis induction. CONCLUSIONS: Results suggest 20% alcohol consumption during 4 months generates differential effects on oral health of rats, depending on its pathophysiological state: It would exacerbate the inflammatory condition when periodontal damage is absent, but it would not when damage is installed.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Dinoprostona/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Enfermedades Periodontales/metabolismo , Enfermedades Periodontales/patología , Pérdida de Hueso Alveolar/inducido químicamente , Animales , Biomarcadores/metabolismo , Encía/efectos de los fármacos , Encía/metabolismo , Lipopolisacáridos , Masculino , Enfermedades Periodontales/inducido químicamente , Ratas , Glándula Submandibular/efectos de los fármacos , Glándula Submandibular/metabolismo , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To investigate whether cholinergic ganglionic stimulus modifies the release of gonadotropin-releasing hormone (GnRH), catecholamines, and progesterone at the ovarian level. DESIGN: Animal study. SETTING: University animal laboratory. ANIMAL(S): Six to eight virgin adult Holtzman rats. INTERVENTION(S): Superior mesenteric ganglion-ovarian nerve plexus-ovary system removed and placed in one cuvette with two compartments, with acetylcholine added to the ganglion in the experimental group. MAIN OUTCOME MEASURE(S): Measurement of ovarian liquid obtained from catecholamines by high-performance liquid chromatography; measurement of progesterone (P(4)), GnRH, and luteinizing hormone (LH) by radioimmunoassay; and measurement of gene expression of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and 20α-hydroxysteroid dehydrogenase (20α-HSD) by reverse-transcriptase polymerase chain reaction (RT-PCR). RESULT(S): The study focused on the estrus and diestrus II (DII) stages. On the estrus days, the release of GnRH, NA, and 20α-HSD increased, while P(4) and 3ß-HSD decreased. On the DII days, GnRH, P(4), and 3ß-HSD increased, while 20α-HSD and NA decreased. The ovarian liquid with GnRH showed biologic activity, namely, an increase in LH release during the DII stage and a decrease during the estrus stage. CONCLUSION(S): Neural stimulus from the superior mesenteric ganglion influences the release of NA, adrenaline, and GnRH. We also have demonstrated that these neurotransmitters participate in the atretogenic processes of the ovary, thus providing evidence of the necessity of the sympathetic neural pathway.
Asunto(s)
Catecolaminas/metabolismo , Ganglios Simpáticos/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Ovario/inervación , Ovario/metabolismo , Progesterona/metabolismo , Receptores Colinérgicos/metabolismo , 20-alfa-Hidroxiesteroide Deshidrogenasa/genética , 20-alfa-Hidroxiesteroide Deshidrogenasa/metabolismo , 3-Hidroxiesteroide Deshidrogenasas/genética , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Acetilcolina/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Diestro/metabolismo , Estro/metabolismo , Femenino , Ovario/enzimología , ARN Mensajero/metabolismo , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de TiempoRESUMEN
OBJECTIVE: Evidence exists of the anti-inflammatory and immunological properties of endocannabinoids in various tissues; the aim of the present study was therefore to assess the effect of long-term treatment with the synthetic cannabinoid methanandamide (Meth-AEA) on the progression of periodontitis in rats. MATERIALS AND METHODS: Periodontitis was induced by injecting LPS (1 mg/ml) into the gingiva around the neck of the first upper and lower molars, and into the inter-dental space between the first and second molars. This protocol was repeated for 6 weeks on days 1, 3, and 5 of each week. RESULTS: Long-term treatment with topical Meth-AEA (500 ng/ml), applied daily to gingival tissue of rats induced with periodontitis, significantly diminished the alveolar bone loss, measured as the distance between the cemento-enamel junction and the alveolar crest, in both maxillary and mandibular first molars, compared to rats without treatment (P < 0.05). The treatment also reduced the production of some biological mediators of periodontal disease augmented by LPS, such as tumor necrosis factor alpha (from 119.4 ± 9.9 pg/mg protein to 75.1 ± 10.8, P < 0.05) and nitric oxide produced by inducible nitric oxide synthase (from 507.7 ± 107.1 pmol/min/mg protein to 163.1 ± 53.9, P < 0.01). CONCLUSION: These results demonstrate the beneficial effects of treatment with Meth-AEA on gingival tissue of rats with periodontitis.
Asunto(s)
Pérdida de Hueso Alveolar/prevención & control , Antiinflamatorios/uso terapéutico , Ácidos Araquidónicos/uso terapéutico , Periodontitis/tratamiento farmacológico , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Animales , Antiinflamatorios/farmacología , Ácidos Araquidónicos/farmacología , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Técnicas In Vitro , Lipopolisacáridos , Masculino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Periodontitis/inducido químicamente , Periodontitis/metabolismo , Periodontitis/patología , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/agonistas , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to assess the short term effect of ethanol administration on periodontal disease in rats. DESIGN: Rats received either ethanol 2g/kg or water by gastric gavage twice a day. On the fifth day ligatures were tied around the molars of half of the rats to induce periodontitis. After 7days gingival tissue was removed and assayed for inflammatory markers. Finally, hemi-mandibles were extracted to evaluate bone loss by histomorphometrical techniques. RESULTS: The experimental periodontitis increased significantly the mRNA expression (p<0.001) and activity (p<0.001) of inducible nitric oxide synthase (iNOS) in the gingival tissue, whilst short time ethanol administration increased iNOS activity (p<0.05) and produced an additive effect on iNOS mRNA expression augmented by periodontitis (p<0.01). The short time ethanol administration also potentiated the periodontitis stimulatory effect on the mRNA expression of interleukin (IL)-1ß (p<0.01 and p<0.001, in semi-quantitative and real time PCR, respectively) and on the height of periodontal ligament (p<0.05). However, the ligature-induced periodontitis, but not ethanol administration, increased the prostaglandin E(2) content (p<0.05) and, diminished the alveolar bone volume (p<0.05), as compared to sham rats. CONCLUSION: The present results suggest that ethanol consumption could represent a risk indicator for periodontal disease since augments the expression of inflammatory markers, in healthy rats, and increases them, at short term, during the illness. However, scale longitudinal investigation and more case-control studies are needed to confirm this statement.
Asunto(s)
Bebidas Alcohólicas/efectos adversos , Etanol/efectos adversos , Mediadores de Inflamación/análisis , Periodontitis/patología , Pérdida de Hueso Alveolar/patología , Proceso Alveolar/patología , Animales , Antiinflamatorios/sangre , Biomarcadores/análisis , Cromatografía Líquida de Alta Presión , Corticosterona/sangre , Dinoprostona/análisis , Encía/química , Encía/enzimología , Interleucina-1beta/análisis , Masculino , Óxido Nítrico Sintasa de Tipo II/análisis , Ligamento Periodontal/patología , Periodontitis/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de RiesgoRESUMEN
LHRH release from hypothalamus is influenced by the neurotransmitter glutamate that acts, among others, on NMDA receptors present in LHRH neurons. On the other hand, the neurosteroid allopregnanolone can modulate the activity of specific neurotransmitter receptors and affect neurotransmitter release. We examined the role of allopregnanolone on in vitro LHRH and glutamate release from mediobasal hypothalamus and anterior preoptic area of ovariectomized rats with estrogen and progesterone replacement. Moreover, we evaluated whether the neurosteroid might act through modulation of NMDA receptors. Allopregnanolone induced an increase in LHRH release. This effect was reversed when the NMDA receptors were blocked by the NMDA antagonist 2-amino-7-phosphonoheptanoic acid (AP-7) indicating that this neurosteroid would interact with NMDA receptors. Moreover allopregnanolone induced an augment in K(+) evoked [(3)H]-glutamate release from mediobasal hypothalamus-anterior preoptic area explants and this effect was also reversed when NMDA receptors were blocked with AP-7. These results suggest an important physiologic function of allopregnanolone on the regulation of neuroendocrine function in female adult rats. Not only appears to be involved in enhancing LHRH release through modulation of NMDA receptors but also in the release of glutamate which is critical in the control of LHRH release.
Asunto(s)
Ácido Glutámico/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Neurotransmisores/farmacología , Pregnanolona/farmacología , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , 2-Amino-5-fosfonovalerato/análogos & derivados , 2-Amino-5-fosfonovalerato/farmacología , Animales , Terapia de Reemplazo de Estrógeno , Femenino , Hipotálamo/efectos de los fármacos , Técnicas In Vitro , Modelos Animales , N-Metilaspartato/farmacología , Ovariectomía , Área Preóptica/efectos de los fármacos , Área Preóptica/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/fisiologíaRESUMEN
This study investigated the participation of the hypothalamic endocannabinoid system in the response to lipopolysaccharide (LPS) challenge evaluating oxytocin (OXT) and tumor necrosis factor-alpha (TNF-alpha) plasma levels in vivo and their release from hypothalamic fragments in vitro. LPS increased OXT and TNF-alpha release through anandamide-activation of hypothalamic cannabinoid receptor CB(1,) since the antagonist AM251 blocked this effect. Anandamide, through its receptors, also increased hypothalamic nitric oxide (NO) which inhibited OXT release, ending the stimulatory effect of the endocannabinoid. Our findings reveal a hypothalamic interaction between oxytocin, endocannabinoid and NO-ergic systems providing a regulation of the hypothalamic-neurohypophyseal axis under basal and stress conditions.
Asunto(s)
Moduladores de Receptores de Cannabinoides/metabolismo , Endocannabinoides , Hipotálamo/efectos de los fármacos , Lipopolisacáridos/farmacología , Oxitocina/sangre , Factor de Necrosis Tumoral alfa/sangre , Análisis de Varianza , Animales , Ácidos Araquidónicos/farmacología , Benzamidas/farmacología , Moduladores de Receptores de Cannabinoides/antagonistas & inhibidores , Moduladores de Receptores de Cannabinoides/farmacología , Carbamatos/farmacología , Ensayo de Inmunoadsorción Enzimática/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Hipotálamo/metabolismo , Indoles/farmacología , Masculino , Óxido Nítrico/metabolismo , Alcamidas Poliinsaturadas/farmacología , Radioinmunoensayo/métodos , Ratas , Ratas Sprague-Dawley , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismoRESUMEN
The hypothalamo-neurohypophyseal system plays a role in homeostasis under a variety of stress conditions, including endotoxemia. Oxytocin (OXT) and vasopressin (VP) are important hormones synthesized by neurons in the hypothalamic paraventricular and supraoptic nuclei and released into different brain regions and from the neurohypophyseal terminals into the blood in response to many patho-physiological stimuli. However, the mechanism that controls OXT and VP secretion has not been fully elucidated. Nitric oxide (NO) is a known mediator that regulates the release of these hormones. The endocannabinoid system is a new intercellular system that modulates several neuroendocrine actions. Endocannabinoids (eCB) are released as retrograde messengers by many neurons, including hypothalamic magnocellular neurons and cannabinoid receptors are localized within these neurons, as well as in the anterior and posterior pituitary lobes, suggesting an eCB role in the production and release of OXT and VP. Lipopolysaccharide (LPS) injection is a model used as immune challenge. LPS causes a neuroendocrine response that is mediated by cytokines, tumor necrosis factor-alpha being one of them. We focused on NO and endocannabinoid system participation on OXT and VP production and secretion during basal and stress conditions and found that eCB affect basal OXT and VP secretion by acting differently at each level of the hypothalamo-neurohypophyseal system. After LPS, there is an increase in eCB synthesis that enhances OXT secretion.
Asunto(s)
Moduladores de Receptores de Cannabinoides/metabolismo , Endocannabinoides , Sistema Hipotálamo-Hipofisario/metabolismo , Sistemas Neurosecretores/metabolismo , Oxitocina/metabolismo , Estrés Fisiológico/inmunología , Vasopresinas/metabolismo , Animales , Citocinas/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/inmunología , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/fisiopatología , Sistemas Neurosecretores/inmunología , Óxido Nítrico/metabolismoRESUMEN
Nitric oxide (NO) was initially described as a mediator of endothelial relaxation, and now its participation is recognized in numerous physiological and pathological processes. It was demonstrated that lipopolysaccharide-stimulated corticotropin-releasing factor release involves NO production. Furthermore, it has been shown that interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, IL-6, and IL-2 can stimulate adrenocorticotropic hormone release from anterior pituitary via NO. Also, we found that NO released from hypothalamic NOergic neurons in response to norepinephrine diffuses to luteinizing hormone-releasing hormone (LHRH) neurons that activate cyclooxygenase and guanylate cyclase. This activation results in an increase in prostaglandin E2 and cyclic guanosine monophosphate, respectively, which leads to the exocytosis of LHRH granules. During pathological conditions, such as manganese intoxication, NO production is increased, leading to an increase in LHRH secretion that can advance puberty. In another study we demonstrated that NO reduces oxytocin as well as vasopressin secretion from the posterior pituitary, suggesting it has a modulatory role during dehydration. An increase in NO synthase (NOS) activity and protein in the hippocampus and cerebellum was found in offspring of rats that were subjected to prenatal stress, and this was correlated with behavioral changes in adults. Also NO participates in signal transduction pathways in peripheral tissue in physiological processes, such as in corticosterone release from the adrenal gland. Pathological conditions, such as tumors of the head and neck, that are treated with radiation are followed by xerostomy. In a rat model, radiation diminished NOS activity in the submandibulary gland, and this was followed by inhibition in salivary secretion. In summary, this review describes the wide participation of NO in the cross-talk between neuroendocrine and neuroimmune systems in physiological and pathological processes.
Asunto(s)
Sistema Inmunológico/metabolismo , Sistemas Neurosecretores/metabolismo , Óxido Nítrico/metabolismo , Animales , Corticosterona/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/metabolismoRESUMEN
Manganese chloride (MnCl2) is capable of stimulating luteinizing hormone releasing hormone (LHRH) secretion in adult male Sprague-Dawley rats through the activation of the hypothalamic nitric oxide/cyclic guanosine monophosphate (cGMP)/protein kinase G pathway. The present study aimed to determine the involvement of specific neurotransmitters involved in this action. Our results indicate that dopamine, but not glutamic acid and prostaglandins, mediates the MnCl2 stimulated secretion of LHRH from medial basal hypothalami in vitro, as well as increases the activity of nitric oxide synthase. Furthermore, a biphasic response was observed in that gamma aminobutyric acid (GABA) release was also increased, which acts to attenuate the MnCl2 action to stimulate LHRH secretion. Although it is clear that manganese (Mn+2) can acutely induce LHRH secretion in adult males, we suggest that the additional action of MnCl2 to release GABA, a LHRH inhibitor, may ultimately contribute to suppressed reproductive function observed in adult animals following exposure to high chromic levels of Mn+2.
Asunto(s)
Cloruros/toxicidad , Dopamina/metabolismo , Disruptores Endocrinos/toxicidad , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/efectos de los fármacos , Ácido gamma-Aminobutírico/metabolismo , Factores de Edad , Animales , Cloruro de Calcio/farmacología , Ácido Glutámico/metabolismo , Hormona Liberadora de Gonadotropina/sangre , Hipotálamo/metabolismo , Masculino , Compuestos de Manganeso , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Prolactina/sangre , Prostaglandinas/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
During marijuana and alcohol consumption as well as during inflammation the reproductive axis is inhibited, mainly through the inhibition of luteinizing hormone-releasing hormone release. In male rats, this inhibitory effect is mediated, at least in part, by the activation of hypothalamic cannabinoid type 1 receptors (CB1). During inflammation, this activation of the endocannabinoid system seems to be mediated by an increase in TNF-alpha production followed by anandamide augmentations, similarly the effect of intragastric administration of ethanol (3 g/kg) seems to be due to an increase in anandamide. On the other hand, a number of different actions mediated by the endocannabinoid system in various organs and tissues have been described. Both cannabinoid receptors, CB1 and CB2, are localized in the submandibular gland where they mediate the inhibitory effect of intrasubmandibular injections of the endocannabinoid anandamide (6 x 10(-5)M) on salivary secretion. Lipopolysaccharide (5 mg/kg/3 h) injected intraperitoneally and ethanol (3 g/kg/1 h) injected intragastrically inhibited the salivary secretion induced by the sialogogue metacholine; this inhibitory effect was blocked by CB1 and/or CB2 receptor antagonists. Similar to the hypothalamus, these effects seem to be mediated by increased anandamide. In summary, similar mechanisms mediate the inhibitory actions of endocannabinoids and cannabinoids in both hypothalamus and submandibular gland during drug consumption and inflammation.
Asunto(s)
Moduladores de Receptores de Cannabinoides/fisiología , Endocannabinoides , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Inflamación/tratamiento farmacológico , Glándulas Salivales/efectos de los fármacos , Factor de Necrosis Tumoral alfa/fisiología , Animales , Ácidos Araquidónicos/metabolismo , Cannabinoides/farmacología , Etanol/farmacología , Humanos , Sistema Hipotálamo-Hipofisario/inmunología , Sistema Hipotálamo-Hipofisario/metabolismo , Inflamación/inmunología , Alcamidas Poliinsaturadas/metabolismo , Receptores de Cannabinoides/efectos de los fármacos , Receptores de Cannabinoides/inmunología , Glándulas Salivales/inmunología , Glándulas Salivales/metabolismoRESUMEN
Recently studies have demonstrated that low doses of (Mn(+2)) in the form of manganese chloride can stimulate specific puberty-related hormones and advance signs of pubertal development in immature female and male rats. In the present study, we used an in vitro system to evaluate the ability of 0, 50, 250, and 500 microM doses of Mn(+2) to stimulate luteinizing hormone-releasing hormone (LHRH) secretion and to assess the hypothalamic mechanism of this action in adult male Sprague-Dawley rats. We demonstrated that Mn(+2) at 500 microM, but not the lower doses, increased LHRH release, nitric oxide (NO) synthase (NOS) activity, and the content of cyclic cGMP in the medial basal hypothalamus. Inhibition of NOS with a competitive inhibitor (Nomega-nitro-L-arginine methyl ester hydrochloride) prevented the Mn-induced increase in LHRH release. Additionally, methylene blue and KT5823, specific inhibitors of guanylyl cyclase and protein kinase G (PKG), respectively, also blocked the stimulatory effect of Mn(+2) on LHRH release. These in vitro studies demonstrated that the hypothalamic mechanism of Mn(+2) action in adult males is by activation of the NOS/NO system, resulting in increases in cGMP and PKG and thus the secretion of LHRH from the nerve terminals. These results indicate Mn(+2) can cause LHRH release in adult males, and this action is discussed in relation to age, gender, as well as mechanistic and functional differences between adult and immature animals.
Asunto(s)
Cloruros/toxicidad , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factores de Edad , Animales , Carbazoles/farmacología , GMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Guanilato Ciclasa/antagonistas & inhibidores , Guanilato Ciclasa/metabolismo , Hemoglobinas/metabolismo , Hipotálamo/metabolismo , Técnicas In Vitro , Indoles/farmacología , Masculino , Compuestos de Manganeso , Azul de Metileno/farmacología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
OBJECTIVE: In the present work, we evaluated the effect of exposing the submandibular glands (SMG) to radiation, studying different functional parameters such as salivary secretion, nitric oxide (NO) production, reactive oxygen species formation, prostaglandin (PGE) content and apoptosis. METHODS: We irradiated rats in the head and neck region with a single dose of gamma-ray radiation of 15 Gy. Two hours after radiation, we measured norepinephrine-induced salivary secretion. After that, the SMG were dissected, and in this tissue, we measured the activity of NO synthase (NOS), the PGE content, the amount of reactive oxygen species, apoptotic cells and mitochondrial inducible NOS (iNOS) expression. RESULTS: We found that radiation decreased salivary secretion when 10 and 30 microg/kg of norepinephrine was administered via the right femoral vein. We observed that iNOS activity was reduced and PGE content increased after radiation in SMG, indicating that NO and PGEs may participate in salivary secretion. The expression of mitochondrial NOS was increased after radiation leading to the formation of large amounts of NO that acts as a proapoptotic signal. In fact, we observed an augmentation in apoptotic cells. In this study, we also observed an increase in lipid peroxidation induced by radiation that may contribute to tissue damage. CONCLUSIONS: Our results indicate that radiation induced a decrease in salivary secretion and SMG iNOS activity, meanwhile the PGE content, the lipid peroxidation and apoptosis increased in the tissue. These modifications decrease salivary secretion.
Asunto(s)
Óxido Nítrico/efectos de la radiación , Prostaglandinas/efectos de la radiación , Radioterapia/efectos adversos , Glándula Submandibular/metabolismo , Glándula Submandibular/efectos de la radiación , Xerostomía/fisiopatología , Animales , Apoptosis/fisiología , Apoptosis/efectos de la radiación , Modelos Animales de Enfermedad , Regulación hacia Abajo/fisiología , Regulación hacia Abajo/efectos de la radiación , Células Epiteliales/metabolismo , Células Epiteliales/efectos de la radiación , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Peroxidación de Lípido/fisiología , Peroxidación de Lípido/efectos de la radiación , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/efectos de la radiación , Estrés Oxidativo/fisiología , Estrés Oxidativo/efectos de la radiación , Prostaglandinas/metabolismo , Ratas , Saliva/metabolismo , Glándula Submandibular/fisiopatología , Xerostomía/etiología , Xerostomía/metabolismoRESUMEN
The adrenal cortex is a major stress organ in mammals that reacts rapidly to a multitude of external and internal stressors. Adrenocorticotropin (ACTH) is the main stimulator of the adrenal cortex, activating corticosteroid synthesis and secretion. We evaluated the mechanism of action of ACTH on adrenals of male rats, preserving the architecture of the gland in vitro. We demonstrated that both sodium nitroprusside (NP), a nitric oxide (NO) donor, and ACTH stimulate corticosterone release. NO mediated the acute response to ACTH because Nomega-nitro-l-arginine methyl ester, a NO synthase inhibitor, and hemoglobin, a NO scavenger, blocked the stimulation of corticosterone release induced by ACTH. NP stimulated prostaglandin E release, which in turn stimulated corticosterone release from the adrenal. Additionally, indomethacin, which inhibits cyclooxygenase, and thereby, prostaglandin release, prevented corticosterone release from the adrenal induced by both NP and ACTH, demonstrating that prostaglandins mediate acute corticosterone release. Corticosterone content in adrenals after incubation with ACTH or NP was lower than in control glands, indicating that any de novo synthesis of corticosterone during this period was not sufficient to keep up with the release of the stored hormone. The release induced by ACTH or NP depleted the corticosterone content in the adrenal by approximately 40% compared with the content of glands incubated in buffer. The mechanism of rapid release is as follows: NO produced by NO synthase activation by ACTH activates cyclooxygenase, which generates PGE(2), which in turn releases corticosterone stored in microvesicles and other organelles.