RESUMO
Capsaicin, a pungent compound in chili peppers, is described as having potent anti-inflammatory, antioxidant, and antimicrobial properties. It is also described as a potential modulator of the immune system and intestinal microbiota. Oral or rectal administration of capsaicin has been studied to treat or prevent colitis. However, those vias are often not well accepted due to the burning sensation that capsaicin can cause. Our objective was to evaluate whether the application of capsaicin skin creams (0.075%) would be effective in improving inflammation and epithelial barrier function as well as the composition of the gut microbiota in a model of mild colitis induced by dextran sulfate sodium (1.5%). The results showed that the cutaneous application of capsaicin reversed weight loss and decreased colon shortening and diarrhea, all typical signs of colitis. There was also an improvement in the intestinal epithelial barrier, preserving proteins from tight junctions. We also evaluated the biodistribution of 99mtechnetium-radiolabeled capsaicin (99mTc-CAPS) applied to the back skin of the animals. We found significant concentrations of 99 mTc-Cap in the colon and small intestine after 2 and 4 h of administration. In addition, there was an increased expression of capsaicin receptor TRPV1 in the colon. Moreover, animals with colitis receiving cutaneous capsaicin presented a better short-chain fatty acid profile and increased levels of SIgA, suggesting increased microbiota diversity. In conclusion, our work opens avenues for further studies to better understand capsaicin's potential benefits and mechanisms in addressing colitis through cutaneous application.
RESUMO
We investigated the effect of dietary supplementation with kinkan orange on growth, adiposity, metabolic parameters, and oxidative stress in rats with diet-induced hypercholesterolemia. Female Wistar rats (6-8 weeks) were fed a AIN-93M diet (Control); AIN-93M diet containing 5% kinkan orange (CTkinkan); Hypercholesterolemic diet, containing 1% cholesterol and 25% fat (Hyper); or Hypercholesterolemic diet containing 5% kinkan orange (Hyperkinkan). Hypercholesterolemic diet increased body weight, adiposity, serum alanine transaminase (ALT), creatinine, cholesterol and triglycerides, hepatic total lipids, cholesterol, and triglycerides, and hepatic oxidative stress. Supplementation with kinkan reduced the serum and hepatic lipid content, decreased serum ALT, besides improving the antioxidant status in liver tissue of hypercholesterolemic animals. Moreover, HDL-cholesterol increased in both groups supplemented with kinkan orange (CTkinkan and Hyperkinkan). Our data suggest that diet supplementation with kinkan orange may consist of a valid strategy to prevent or reduce dyslipidemia and oxidative stress in hypercholesterolemic rats.
Assuntos
Citrus sinensis , Dislipidemias , Alanina Transaminase , Animais , Colesterol , Citrus sinensis/metabolismo , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Dislipidemias/prevenção & controle , Feminino , Fígado , Obesidade/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , TriglicerídeosRESUMO
Gluten is only partially digested by intestinal enzymes and can generate peptides that can alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of colitis. Therefore, we investigate the effects of wheat gluten-containing diet on the evolution of sodium dextran sulphate (DSS)-induced colitis. Mice were fed a standard diet without (colitis group) or with 4·5 % wheat gluten (colitis + gluten) for 15 d and received DSS solution (1·5 %, w/v) instead of water during the last 7 d. Compared with the colitis group, colitis + gluten mice presented a worse clinical score, a larger extension of colonic injury area, and increased mucosal inflammation. Both intestinal permeability and bacterial translocation were increased, propitiating bacteria migration for peripheral organs. The mechanism by which diet with gluten exacerbates colitis appears to be related to changes in protein production and organisation in adhesion junctions and desmosomes. The protein α-E-catenin was especially reduced in mice fed gluten, which compromised the localisation of E-cadherin and ß-catenin proteins, weakening the structure of desmosomes. The epithelial damage caused by gluten included shortening of microvilli, a high number of digestive vacuoles, and changes in the endosome/lysosome system. In conclusion, our results show that wheat gluten-containing diet exacerbates the mucosal damage caused by colitis, reducing intestinal barrier function and increasing bacterial translocation. These effects are related to the induction of weakness and disorganisation of adhesion junctions and desmosomes as well as shortening of microvilli and modification of the endocytic vesicle route.
Assuntos
Translocação Bacteriana/imunologia , Colite/imunologia , Dieta/efeitos adversos , Glutens/efeitos adversos , Junções Íntimas/imunologia , Animais , Colite/induzido quimicamente , Colite/microbiologia , Colo , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/imunologia , Mucosa Intestinal/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade , Triticum/químicaRESUMO
Apolipoprotein E deficient (Apo E-/-) mice are more resistant to the development of obesity compared to C57BL/6 wild type mice. They also hold a high basal oxidative status due to the loss of antioxidant action of apolipoprotein E. Since obesity is also an inducer of inflammation, we studied the effect of high-fat diet on obesity and oxidative stress in C57BL/6 and Apo E-/- mice for 9 weeks. The results confirmed that Apo E-/- mice fed high-fat diet are more resistant to the increase of both body weight and adiposity compared to C57BL/6 mice. Despite this, Apo E-/- mice presented a higher basal oxidative stress that was enhanced by high-fat diet. Macrophage infiltration, macrophage forming crown-like structures and proinflammatory adipokines (interleukin 6 and tumor necrosis factor alpha) were all higher in adipose tissue from Apo E-/- compared to C57BL/6 mice, regardless of diet type. In conclusion, although Apo E-/- mice are more resistant to becoming obese, they develop more severe adipose tissue inflammation companied by its consequences.
Assuntos
Tecido Adiposo/patologia , Apolipoproteínas E/deficiência , Dieta Hiperlipídica/efeitos adversos , Inflamação/etiologia , Estresse Oxidativo/fisiologia , Tecido Adiposo/metabolismo , Animais , Inflamação/metabolismo , Interleucina-6/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: Extracts of the mushroom Agaricus blazei (A. blazei) have been described as possessing immunomodulatory and potentially cancer-protective activities. However, these effects of A. blazei as a functional food have not been fully investigated in vivo. METHODS: Using apolipoprotein E-deficient (ApoE(-/-)) mice, an experimental model of atherosclerosis, we evaluated the effects of 6 or 12 weeks of A. blazei supplementation on the activation of immune cells in the spleen and blood and on the development of atherosclerosis. RESULTS: Food intake, weight gain, blood lipid profile, and glycemia were similar between the groups. To evaluate leukocyte homing and activation, mice were injected with (99m)Tc-radiolabeled leukocytes, which showed enhanced leukocyte migration to the spleen and heart of A. blazei-supplemented animals. Analysis of the spleen showed higher levels of activation of neutrophils, NKT cells, and monocytes as well as increased production of TNF-α and IFN-γ. Circulating NKT cells and monocytes were also more activated in the supplemented group. Atherosclerotic lesion areas were larger in the aorta of supplemented mice and exhibited increased numbers of macrophages and neutrophils and a thinner fibrous cap. A. blazei-induced transcriptional upregulation of molecules linked to macrophage activation (CD36, TLR4), neutrophil chemotaxy (CXCL1), leukocyte adhesion (VCAM-1), and plaque vulnerability (MMP9) were seen after 12 weeks of supplementation. CONCLUSIONS: This is the first in vivo study showing that the immunostimulatory effect of A. blazei has proatherogenic repercussions. A. blazei enhances local and systemic inflammation, upregulating pro-inflammatory molecules, and enhancing leukocyte homing to atherosclerosis sites without affecting the lipoprotein profile.
Assuntos
Agaricus/química , Aterosclerose/fisiopatologia , Suplementos Nutricionais , Fatores Imunológicos/farmacologia , Inflamação/fisiopatologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Apolipoproteínas E/deficiência , Aterosclerose/imunologia , Antígenos CD36/genética , Antígenos CD36/metabolismo , Adesão Celular , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Modelos Animais de Doenças , Carpóforos/química , Inflamação/imunologia , Interferon gama/imunologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Monócitos/imunologia , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/imunologia , Neutrófilos/imunologia , Peroxidase/genética , Peroxidase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Baço/imunologia , Baço/metabolismo , Baço/patologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
BACKGROUND: This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines. METHODS: Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \ groups (control, colitis, HFD and colitis + HFD). RESULTS: Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group. CONCLUSION: Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream.