RESUMO
The gaseous modulator hydrogen sulfide (H2S) is synthesized, among other routes, by the action of cystathionine-γ-lyase (CSE) and importantly participates in body fluid homeostasis. Therefore, the present study aimed to evaluate the participation of H2S in behavioral, renal and neuroendocrine homeostatic responses triggered by the acute consumption of a high Na+ diet. After habituation, adult male Wistar rats were randomly distributed and maintained for seven days on a control [CD (0.27% of Na+)] or hypersodic diet [HD (0.81% of Na+)]. CD and HD-fed animals were treated with DL-Propargylglycine (PAG, 25 mg/kg/day, ip) or vehicle (0.9% NaCl in equivalent volume) for the same period. At the end of the experiment, animals were euthanized for blood and tissue collection. We demonstrated that a short-term increase in dietary Na+ intake, in values that mimic the variations in human consumption (two times the recommended) significantly modified hydroelectrolytic homeostasis, with repercussions in the hypothalamic-neurohypophysial system and hypothalamic-pituitary-adrenal axis function. These findings were accompanied by the development of a clear inflammatory response in renal tubular cells and microvascular components. On the other hand, the inhibition of the endogenous production of H2S by CSE provided by PAG treatment prevented the inflammation induced by HD. In the kidney, PAG treatment induced the overexpression of inducible nitric oxide synthase in animals fed with HD. Taken together, these data suggest, therefore, that HD-induced H2S production plays an important proinflammatory role in the kidney, apparently counter regulating nitric oxide actions in renal tissue.
Assuntos
Alcinos/farmacologia , Cistationina gama-Liase/antagonistas & inibidores , Glicina/análogos & derivados , Sulfeto de Hidrogênio/antagonistas & inibidores , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Animais , Cistationina gama-Liase/metabolismo , Inibidores Enzimáticos/farmacologia , Aromatizantes/administração & dosagem , Glicina/farmacologia , Homeostase , Sulfeto de Hidrogênio/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Modelos Animais , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Cloreto de Sódio na Dieta/administração & dosagemRESUMO
Opioids are the main group of pharmacological agents used during the perioperative period and provide a sedative and analgesic component. The observations of opioid consumption in West Europe indicate that this group of drugs is widely used in chronic noncancer pain therapy. Nearly 20 years ago, the first publications indicating that opioids, as an element of perioperative pharmacotherapy in oncologic patients, increase the risk of tumor recurrence and affect further prognosis were presented. The actual publications suggest that there are multifactorial, complex mechanisms underlying the immunological impact and carcinogenesis promotion of opioids and that the intensity varies depending on the type of opioid. There are also questions about the immunosuppressive effects among patients receiving opioids in the treatment of chronic noncancer pain. The aim of the review article is to present information about the action of opioids on the immune system in carcinogenic settings and to define the clinical usefulness of this pharmacological phenomenon.
Assuntos
Analgésicos Opioides/efeitos adversos , Carcinogênese , Dor Crônica/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Tolerância a Medicamentos , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Transtornos Relacionados ao Uso de Opioides , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Estudos RetrospectivosRESUMO
Opioids are the main group of pharmacological agents used during the perioperative period and provide a sedative and analgesic component. The observations of opioid consumption in West Europe indicate that this group of drugs is widely used in chronic noncancer pain therapy. Nearly 20 years ago, the first publications indicating that opioids, as an element of perioperative pharmacotherapy in oncologic patients, increase the risk of tumor recurrence and affect further prognosis were presented. The actual publications suggest that there are multifactorial, complex mechanisms underlying the immunological impact and carcinogenesis promotion of opioids and that the intensity varies depending on the type of opioid. There are also questions about the immunosuppressive effects among patients receiving opioids in the treatment of chronic noncancer pain. The aim of the review article is to present information about the action of opioids on the immune system in carcinogenic settings and to define the clinical usefulness of this pharmacological phenomenon.
Assuntos
Humanos , Masculino , Feminino , Dor Crônica/tratamento farmacológico , Carcinogênese , Analgésicos Opioides/efeitos adversos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Estudos Retrospectivos , Tolerância a Medicamentos , Analgésicos Opioides/uso terapêutico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Transtornos Relacionados ao Uso de OpioidesRESUMO
BACKGROUND: Exercise is known to induce multiple beneficial conditioning processes. Conversely, although exercise may generate several hormonal effects, an intrinsic hormonal conditioning process has not been reported. In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we observed inherent and independent conditioning processes of the hypothalamic-pituitary axes in athletes. Our objective is to describe the theory of the novel hormonal conditioning mechanism using the findings from the EROS study. METHODS: In this cross-sectional study, we selected 25 healthy athletes (ATL) and 12 non-physically active healthy controls (NPAC), 18-50 years old, males, with BMI 20-30 kg/m2, with similar baseline characteristics, who underwent gold-standard exercise-independent tests: cosyntropin stimulation test (CST) and insulin tolerance test (ITT), to evaluate cortisol response to CST, and ACTH, cortisol, GH, and prolactin responses to an ITT. RESULTS: Responses to ITT were significantly earlier and higher in ATL than NPAC for cortisol [Mean ± SD: 21.7 ± 3.1 vs 16.9 ± 4.1 µg/dL; p < 0.001], GH [Median (95% CI): 12.73 (1.1-38.1) vs 4.80 (0.33-27.36) µg/L; p = 0.015], and prolactin [24.3 (10.5-67.45) vs 10.50 (6.21-43.44) ng/mL; p = 0.002]. Cortisol response to CST was similar between ATL and NPAC. During ITT, cortisol, GH, and ACTH mean increase in ATL were 52.2, 265.2, and 18.6% higher than NPAC, respectively. Prolactin response was absent in NPAC, while present in ATL. CONCLUSIONS: We found sufficient evidence to propose the existence of a diffuse enhancement of the hypothalamic-pituitary activity in athletes, not restricted to any axis, showing an intrinsic and independent process of "hormonal conditioning" in athletes, similar to those observed in the cardiovascular and neuromuscular systems. This novel conditioning process may be the missing link for understanding the improved responses observed in athletes to harmful situations, traumas, infections, inflammations, and psychiatric conditions.
Assuntos
Atletas/estatística & dados numéricos , Cosintropina/administração & dosagem , Exercício Físico , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Insulina/administração & dosagem , Sistema Hipófise-Suprarrenal/metabolismo , Adolescente , Adulto , Estudos Transversais , Teste de Esforço , Feminino , Hormônios/administração & dosagem , Humanos , Hipoglicemiantes/administração & dosagem , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Prolactina/metabolismo , Adulto JovemAssuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/prevenção & controle , Insuficiência Adrenal/prevenção & controle , Glândulas Suprarrenais/fisiologia , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacosRESUMO
A particular challenge in the development of a bipolar disorder (BD) model in animals is the complicated clinical course of the condition, characterized by manic, depressive and mixed mood episodes. Ouabain (OUA) is an inhibitor of Na+/K+-ATPase enzyme. Intracerebroventricular (ICV) injection of this drug in rats has been regarded a proper model to study BD by mimic specific manic symptoms, which are reversed by lithium (Li), an important mood stabilizer drug. However, further validation of this experimental approach is required to characterize it as an animal model of BD, including depressive-like behaviors. The present study aimed to assess manic- and depressive-like behaviors, potential alteration in the hypothalamic-pituitary-adrenal (HPA) system and oxidative stress parameters after a single OUA ICV administration in adult male Wistar rats. Moreover, we evaluated Li effects in this experimental setting. Data show that OUA ICV administration could constitute a suitable model for BD since the injection of the drug triggered manic- and depressive-like behaviors in the same animal. Additionally, the OUA model mimics significant physiological and neurochemical alterations detected in BD patients, including an increase in oxidative stress and change in HPA axis. Our findings suggest that decreased Na+/K+-ATPase activity detected in bipolar patients may be linked to increased secretion of glucocorticoid hormones and oxidative damage, leading to the marked behavioral swings. The Li administration mitigated these pathological changes in the rats. The proposed OUA model is regarded as suitable to simulate BD by complying with all validities required to a proper animal model of the psychiatric disorder.
Assuntos
Comportamento Animal/efeitos dos fármacos , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/fisiopatologia , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Ouabaína/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Animais , Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Injeções Intraventriculares , Compostos de Lítio/farmacologia , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Ratos WistarRESUMO
CONTEXT: The low-dose (1 µg) ACTH test (LDT) is widely used to assess central adrenal insufficiency (CAI); however, the serum cortisol cutoff value is controversial. Salivary cortisol (SC) may be a more accurate measurement for CAI. OBJECTIVE: To assess a new maximum cutoff value of serum cortisol after LDT in pediatric patients, taking into account serum and SC measurements. DESIGN AND SETTING: Prospective study in a pediatric tertiary referral center. WORKING HYPOTHESIS: The combined analysis of serum and SC response to LDT might improve LDT for CAI diagnosis. PARTICIPANT AND OUTCOME MEASUREMENT: A total of 145 pediatric patients underwent LDT. Serum and SC levels were measured. A central adrenal sufficient (CAS) response was established according to the reference serum cortisol cutoff value of ≥497 nmol/L. RESULTS: The LDT study showed central adrenal sufficiency in 72 patients and CAI in 73 patients. Considering the lower quartile of maximum SC value (21 nmol/L) in the CAS group, an intermediate CAI (InCAI) group and a real CAI (RCAI) group were defined. Regarding the median maximum value of serum cortisol levels in the InCAI group, a new serum cortisol cutoff value of 450 nmol/L was established. Furthermore, 91% of the patients in the RCAI group were below this cutoff value. CONCLUSION: The combined evaluation of maximum serum and SC levels to LDT might be useful to define an InCAI group and to avoid unnecessary hormone replacement therapy. However, rigorous patient follow-up is required.
Assuntos
Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico/farmacologia , Hidrocortisona/sangue , Sistema Hipófise-Suprarrenal/fisiopatologia , Glândulas Salivares/metabolismo , Adolescente , Insuficiência Adrenal/sangue , Hormônio Adrenocorticotrópico/sangue , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pediatria , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
The hypothalamic-pituitary-adrenal axis (HPA) exerts important catabolic peripheral effects and influences autonomic nervous system (ANS)-mediated processes. Impaired negative-feedback control or reduced HPA axis sensitivity and altered ANS activity appear to be associated with the development and maintenance of obesity. In the present study, we examined the hypothesis that the central HPA axis is dysregulated favouring ANS disbalance in monosodium l-glutamate (MSG)-induced rat obesity. Glucose homeostasis, corticosterone, leptin and ANS electrical activity were evaluated. Adult MSG-induced obese rats exhibited fasting hyperinsulinaemia, insulin resistance, glucose intolerance, hypercorticosteronaemia, hyperleptinaemia and altered ANS activity. A decrease in food intake was observed during corticotrophin-releasing hormone (CRH) treatment in both control and MSG-treated rats. By contrast, food intake was significantly elevated in control rats treated with dexamethasone (DEXA), whereas no alterations were observed following DEXA treatment in MSG-induced obese rats. After DEXA injection, an increase in fasting insulin and glucose levels, associated with insulin resistance, was seen in both groups. As expected, there was a decrease of parasympathetic activity and an increase of sympathetic nervous activity in CRH-treated control animals and the opposite effect was seen after DEXA treatment. By contrast, there was no effect on ANS activity in MSG-rats treated with CRH or DEXA. In conclusion, impairment of the HPA axis can lead to disbalance of ANS activity in MSG-treated rats, contributing to the establishment and maintenance of obesity.
Assuntos
Sistema Nervoso Autônomo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Obesidade/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiopatologia , Corticosterona/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Glucose/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Insulina/metabolismo , Masculino , Obesidade/induzido quimicamente , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiopatologia , Ratos Wistar , Glutamato de Sódio/administração & dosagem , Glutamato de Sódio/análogos & derivadosRESUMO
Depression is a common psychiatric disease which pharmacological treatment relieves symptoms, but still far from ideal. Tactile stimulation (TS) has shown beneficial influences in neuropsychiatric disorders, but the mechanism of action is not clear. Here, we evaluated the TS influence when applied on adult female rats previously exposed to a reserpine-induced depression-like animal model. Immediately after reserpine model (1 mg/kg/mL, 1×/day, for 3 days), female Wistar rats were submitted to TS (15 min, 3×/day, for 8 days) or not (unhandled). Imipramine (10 mg/kg/mL) was used as positive control. After behavioral assessments, animals were euthanized to collect plasma and prefrontal cortex (PFC). Behavioral observations in the forced swimming test, splash test, and sucrose preference confirmed the reserpine-induced depression-like behavior, which was reversed by TS. Our findings showed that reserpine increased plasma levels of adrenocorticotropic hormone and corticosterone, decreased brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B, and increased proBDNF immunoreactivity in the PFC, which were also reversed by TS. Moreover, TS reestablished glial fibrillary acidic protein and glucocorticoid receptor levels, decreased by reserpine in PFC, while glial cell line-derived neurotrophic factor was increased by TS per se. Our outcomes are showing that TS applied in adulthood exerts a beneficial influence in depression-like behaviors, modulating the HPA axis and regulating neurotrophic factors more effectively than imipramine. Based on this, our proposal is that TS, in the long term, could be considered a new therapeutic strategy for neuropsychiatric disorders improvement in adult life, which may represent an interesting contribution to conventional pharmacological treatment.
Assuntos
Envelhecimento/fisiologia , Comportamento Animal , Depressão/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Fatores de Crescimento Neural/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Transdução de Sinais , Tato , Hormônio Adrenocorticotrópico/sangue , Animais , Peso Corporal/efeitos dos fármacos , Corticosterona/sangue , Depressão/sangue , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos Wistar , Reserpina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sacarose , NataçãoRESUMO
While physiological levels of glucocorticoids are required to ensure proper functions of the body, consistently high levels may engender several deleterious consequences. We have previously shown an increase in the activity of the hypothalamic-pituitary-adrenal (HPA) axis in rats fed sucrose-rich diets (SRD). The main goal of this study was to analyze the processes involved in the modulation of the pituitary production of ACTH by SRD, and to test melatonin as a possible therapeutic agent for the prevention of the HPA axis dysfunction. Male Wistar rats were fed standard chow and either SRD (30% sucrose in the drinking water) or plain water for three weeks. Melatonin was administered as subcutaneous pellets. Results showed that SRD treatment induced an increase in systemic ACTH and corticosterone levels and a decrease in melatonin levels. In the pituitary gland, we also detected an increase in the expression levels of proopiomelanocortin (POMC) that was accompanied by increased levels of: lipoperoxides, nitro-tyrosine modified proteins, catalase, heme oxygenase-1, interleukin-1ß mRNA, and by an increase in the tissue number of inflammatory cells (F4/80 and Iba-1 positive cells). Melatonin treatment prevented all these systemic and pituitary changes as well as the increase in POMC expression induced by incubation of AtT-20 corticotrophs with conditioned media obtained from stimulated macrophages. In conclusion, stimulation of POMC/ACTH production in rats fed a SRD could involve the generation of oxidative stress and inflammation in the pituitary gland. Melatonin treatment prevented these effects and normalized the activity of the HPA axis.