RESUMO
Previous studies have demonstrated the relevance of several soluble molecules in the pathogenesis of dengue. In this regard, a possible role for angiotensin II (Ang II) in the pathophysiology of dengue has been suggested by the observation of a blockade of Ang II in patients with dengue, increased expression of molecules related to Ang II production in the plasma of dengue patients, increased expression of circulating cytokines and soluble molecules related to the action of Ang II, and an apparent relationship between DENV, Ang II effects, and miRNAs. In addition, in ex vivo experiments, the blockade of Ang II AT1 receptor and ACE-1 (angiotensin converting enzyme 1), both of which are involved in Ang II production and its function, inhibits infection of macrophages by DENV, suggesting a role of Ang II in viral entry or in intracellular viral replication of the virus. Here, we discuss the possible mechanisms of Ang II in the entry and replication of DENV. Ang II has the functions of increasing the expression of DENV entry receptors, creation of clathrin-coated vesicles, and increasing phagocytosis, all of which are involved in DENV entry. This hormone also modulates the expression of the Rab5 and Rab7 proteins, which are important in the endosomal processing of DENV during viral replication. This review summarizes the data related to the possible involvement of Ang II in the entry of DENV into cells and its replication.
Assuntos
Angiotensina II , Vírus da Dengue , Internalização do Vírus , Replicação Viral , Angiotensina II/metabolismo , Humanos , Vírus da Dengue/fisiologia , Vírus da Dengue/genética , Animais , Dengue/virologia , Dengue/metabolismoRESUMO
BACKGROUND: Post-streptococcal glomerulonephritis (PSGN) is a consequence of the infection by group A beta-hemolytic streptococcus. During this infection, various immunological processes generated by streptococcal antigens are triggered, such as the induction of antibodies and immune complexes. This activation of the immune system involves both innate and acquired immunity. The immunological events that occur at the renal level lead to kidney damage with chronic renal failure as well as resolution of the pathological process (in most cases). Angiotensin II (Ang II) is a molecule with vasopressor and pro-inflammatory capacities, being an important factor in various inflammatory processes. During PSGN some events are defined that make Ang II conceivable as a molecule involved in the inflammatory processes during the disease. CONCLUSION: This review is focused on defining which reported events would be related to the presence of this hormone in PSGN.
Assuntos
Angiotensina II , Glomerulonefrite , Infecções Estreptocócicas , Streptococcus pyogenes , Humanos , Glomerulonefrite/imunologia , Glomerulonefrite/microbiologia , Glomerulonefrite/etiologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/imunologia , Animais , Rim/imunologia , Rim/patologiaRESUMO
OBJECTIVE: Metformin (MET) is a drug used in the treatment of type 2 diabetes due to its insulin receptor sensitizing properties and anti-hepatic gluconeogenesis effect. One of the comorbidities in diabetes is the depression. This review aimed at summarizing the results of the available MET, depression and diabetes studies to clarify the possible role of MET in the depression during diabetes. METHODS: A bibliographic search on PubMed, Embase, PsycINFO, Web of Science, Cochrane Central for studies referring to MET, depression and diabetes. RESULTS: Several studies have associated depression to the chronic inflammation that characterizes diabetes. Additionally MET is an anti-inflammatory molecule that generally acts by activating AMPK and inhibiting the NF-kB factor. In the context of diabetes, MET can act directly as an anti-inflammatory drug as well as inhibiting other pro-inflammatory molecules. In this regard, MET may inhibit the pro-inflammatory effects of angiotensin II. By facilitating the action of insulin and reducing hepatic gluconeogenesis, MET reduces circulating glucose levels, decreasing the formation of advanced glycation end products and therefore inflammation. During diabetes, the gut microbiota and the permeability of the intestinal barrier are altered, causing high levels of circulating lipopolysaccharides (LPS), which induce inflammation. MET can normalize the microbiota and the intestinal barrier permeability reducing the levels of LPS and inflammation. Clinical and experimental studies show the anti-depressant effect of MET mediated by different mechanisms both at the peripheral level and in the central nervous system. CONCLUSION: Therefore, MET as an anti-inflammatory drug can decrease symptoms of depression and represents a therapeutic approach to improve the psychological state of patients with diabetes. Additionally, insulin also has an anti-inflammatory effect that could act together with MET.
Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Lipopolissacarídeos , Insulina/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêuticoRESUMO
Post-streptococcal glomerulonephritis is a condition resulting from infection by group A beta-hemolytic streptococcus. The main mechanism involves the formation of immune complexes formed in the circulation or in situ on the glomerular basement membrane, which activates complement and causes various inflammatory processes. Cellular mechanisms have been reported in the induction of kidney damage represented by the infiltration of innate cells (neutrophils and monocyte/macrophages) and adaptive cells (CD4 + lymphocytes and CD8 + lymphocytes) of the immune system. These cells induce kidney damage through various mechanisms. It has been reported that nephritogenic antigens are capable of inducing inflammatory processes early, even before the formation of immune complexes. Usually, this disease progresses towards clinical and renal normalization; however, in a smaller number of patients, it evolves into chronicity and persistent kidney damage. Hypotheses have been proposed regarding the mechanisms underlying this progression to chronicity including failure to induce apoptosis and failure to phagocytose apoptotic cells, allowing these cells to undergo membrane permeabilization and release pro-inflammatory molecules into the environment, thereby perpetuating renal inflammation. Other mechanisms involved include persistent infection, genetic background of the host's complement system, tubulointerstitial changes, and pre-existing kidney damage due to old age and comorbidities.
Assuntos
Glomerulonefrite , Nefropatias , Humanos , Complexo Antígeno-Anticorpo , Glomerulonefrite/etiologia , Inflamação , Apoptose , Doença Aguda , Membrana Basal Glomerular , Nefropatias/complicações , Proteínas do Sistema ComplementoRESUMO
Dengue is a disease caused by a flavivirus that is transmitted principally by the bite of an Aedes aegypti mosquito and represents a major public-health problem. Many studies have been carried out to identify soluble factors that are involved in the pathogenesis of this infection. Cytokines, soluble factors, and oxidative stress have been reported to be involved in the development of severe disease. Angiotensin II (Ang II) is a hormone with the ability to induce the production of cytokines and soluble factors related to the inflammatory processes and coagulation disorders observed in dengue. However, a direct involvement of Ang II in this disease has not been demonstrated. This review primarily summarizes the pathophysiology of dengue, the role of Ang II in various diseases, and reports that are highly suggestive of the involvement of this hormone in dengue.
Assuntos
Aedes , Vírus da Dengue , Dengue , Flavivirus , Animais , Humanos , Vírus da Dengue/fisiologia , Angiotensina II , CitocinasRESUMO
INTRODUCTION: We assessed the association between overweight, obesity, and morbid obesity with the incidence of the most aggressive breast cancer subtypes in women. METHODS AND MATERIALS: A cross-sectional study was performed. We conducted a record review to identify the following aspects: body mass index, sociodemographic features, tumor characteristics, and reproductive and molecular aspects. Descriptive statistics and univariate analysis were performed to identify the association between the molecular subtypes and the study variables. In addition, we used multivariate analysis to identify the association between obesity and the presence of metastatic lymph nodes. RESULTS: We included 1446 women with an average age of 52.5 ± 12.1 years. Of the 1446 patients, 47% were premenopausal and 75% were overweight. Univariate analysis indicated a statistically significant association between obesity and advanced disease stage, as well as nulliparity and multiparity. Similar results were found for women with morbid obesity. Model 1 of the multivariate analysis showed an association between the presence of metastatic lymph nodes and obesity (odds ratio [OR], 1.6; P = .008) and histologic grade 2 or 3 (OR, 2.4; P = .003). Using model 2, an association was identified between an advanced disease stage and 2 factors: morbid obesity (OR, 1.9; P = .02) and positive human epidermal growth factor receptor 2 (OR, 1.8; P = .045). CONCLUSION: We found that obesity is associated with the more advanced stages of breast cancer. Further studies are needed to evaluate the role of obesity in breast cancer progression in women.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Obesidade/complicações , Sobrepeso/complicações , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/etiologia , Carcinoma Ductal de Mama/metabolismo , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Metástase Linfática , México/epidemiologia , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
Mercuric chloride (HgCl2) induces kidney damage, in part, through oxidative stress. A role for angiotensin II (Ang II) in pro-inflammatory events in a model of acute HgCl2-induced nephropathy was reported. Ang II is a potent oxidative stress inducer; however, its role in oxidative/anti-oxidative events in HgCl2-induced nephropathy remains unknown. The aim of this study was to determine the role of Ang II in the oxidative stress and renal infiltration of CD8(+) T-cells after an acute HgCl2 intoxication. Three groups of Sprague Dawley rats were treated with a single subcutaneous dose of 2.5 mg/kg HgCl2: for 3 days prior to and for 4 days after that injection, rats in one group received Losartan (30 mg/kg), in another group Enalapril (30 mg/kg) or normal saline in the last group. Two other groups of drug-treated rats received saline in place of HgCl2. A final group of rats received saline in place of HgCl2 and the test drugs. All treatments were via gastric gavage. At 96 h after the vehicle/HgCl2 injection, blood and kidney samples were harvested. Renal sections were homogenized for measures of malondialdehyde (MDA), reduced glutathione (GSH) and catalase activity. Frozen sections were studied for the presence of superoxide anion ([Formula: see text]) and CD8(+) T-cells. HgCl2-treated rats had increased interstitial and tubular expression of [Formula: see text], high levels of MDA, normal catalase activity and GSH content, increased levels of interstitial CD8(+) T-cells and an increased percentage of necrotic tubules. Anti-Ang II treatments diminished the HgCl2-induced increases in interstitial [Formula: see text], CD8(+) T-cells and tubular damage and increased catalase and GSH expression above that due to HgCl2 alone; the HgCl2-induced high MDA levels were unaffected by the drugs. These data provide new information regarding the potential role of Ang II in the oxidative stress and renal CD8(+) T-cell infiltration that occur during HgCl2 nephropathy.
Assuntos
Angiotensina II/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Nefropatias/imunologia , Rim/metabolismo , Cloreto de Mercúrio/administração & dosagem , Estresse Oxidativo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Linfócitos T CD8-Positivos/imunologia , Catalase/metabolismo , Enalapril/administração & dosagem , Glutationa/metabolismo , Rim/imunologia , Rim/patologia , Nefropatias/induzido quimicamente , Losartan/administração & dosagem , Masculino , Malondialdeído/metabolismo , Cloreto de Mercúrio/toxicidade , Necrose , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1ß production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1ß production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.
Assuntos
Vírus da Dengue/efeitos dos fármacos , Dengue/tratamento farmacológico , Enalapril/administração & dosagem , Interleucina-1beta/imunologia , Losartan/administração & dosagem , Macrófagos/imunologia , Ligação Viral/efeitos dos fármacos , Animais , Culicidae , Dengue/genética , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/fisiologia , Humanos , Interleucina-1beta/genética , Masculino , CamundongosRESUMO
Venezuelan equine encephalitis (VEE) is a viral disease transmitted by mosquitoes. The inflammation induced by the VEE virus is associated with a high mortality rate in mice. Angiotensin II (Ang II), a pro-inflammatory molecule, is produced in the normal rat brain. There is no information about the role of this molecule in the inflammatory events occurring during VEE and the effect of inflammation on the mortality rate in VEE-virus-infected rats. This study was designed to determine the role of Ang II in VEE and to analyze the effect of inflammation on mortality in infected rats. Two groups of rats were studied: 1) Virus-infected animals and controls (n = 60) were treated with losartan (a blocker of the Ang II-AT1 receptor) or with pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) or left untreated and analyzed for morbidity and mortality. 2) Animals treated using the same protocol (n = 30) were sacrificed at day 4 postinfection and analyzed by immunohistochemistry and histopathology and for cytokine production. Increased expression of Ang II, ICAM-1, ED-1 and cytokines (IL-1α, MCP-1, IL-6 and IL-10) in infected animals was observed. The main histopathology findings were dilated capillaries and capillaries with endothelial detachment. Losartan and PDTC reduced the expression of IL-1α, MCP-1, and IL-10, and the number of dilated capillaries and capillaries with endothelial detachment. Survival analysis showed that 100% mortality was reached earlier in infected rats treated with losartan (day 14) or PDTC (day 11) than in untreated animals (day 19). These findings suggest that Ang II plays a role in VEE and that brain inflammation is protective against viral infection.
Assuntos
Angiotensina II/metabolismo , Vírus da Encefalite Equina Venezuelana/fisiologia , Encefalomielite Equina Venezuelana/metabolismo , Encefalomielite Equina Venezuelana/virologia , Angiotensina II/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Vírus da Encefalite Equina Venezuelana/genética , Encefalomielite Equina Venezuelana/genética , Encefalomielite Equina Venezuelana/mortalidade , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
Manganese (Mn) is able to cross the blood-brain barrier and induces functional and structural alterations during the intoxication by this metal. Therefore, the effects of chronic administration of Mn in the caudate nucleus of mice were evaluated by electron microscopy. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/kg/d) 5 d per week during 9 weeks. The control group received only 0.9% of NaCl solution. The caudate nuclei were extracted and subsequently processed to be observed on a conventional transmission electron microscope at 2, 4, 6, and 9 weeks after treatment. A high percentage of vacuolated and swollen mitochondria were found throughout all the analyzed periods. Myelin disarrangement and ultrastructural alterations related to edema were observed increased in Mn-treated mice at week 9. Granular degeneration of myelin at week 9 accompanied with deposition of electron dense granules in the neuropil was also observed. Edema in neuropil and glial cells was detected from week 2 to week 9 accompanied by swollen mitochondria. Neuronal bodies, synaptic terminals, and perivascular cells were found swollen. Decreased electron density in postsynaptic areas and decreased and dispersed synaptic vesicles in presynaptic areas were noted in Mn-treated animals. Some neurons from Mn-treated mice showed cisternae dilation of the Golgi apparatus. These results suggest that Mn-treatment produces structural alterations in the caudate nucleus that could be responsible for some of the neurotoxic effects of this metal.