RESUMO
The present work evaluated how a native pea protein isolate (PPI) affects the key roles carried out by bile salts (BS) in lipid digestion by means of the in vitro static INFOGEST protocol. Two gastric residence times were evaluated (10 and 60 min), and then the peptides obtained (GPPP) were mixed with BS at physiological concentration in simulated intestinal fluid to understand how they interact with BS both at the bulk and at the interface. Both GPPP give rise to a film with a predominant viscous character that does not constitute a barrier to the penetration of BS, but interact with BS in the bulk duodenal fluid. When the peptides flushing from the stomach after the different gastric residence times undergo duodenal digestion, it was found that for the longer gastric residence time the percentage of soluble fraction in the duodenal phase, that perform synergistically with BS micelles, was twice that of the lower residence time, leading to an increase in the solubilization of oleic acid. These results finally lead to a greater extent of lipolysis of olive oil emulsions. This work demonstrates the usefulness of in vitro models as a starting point to study the influence of gastric residence time of pea protein on its interaction with BS, affecting lipolysis. Pea proteins were shown to be effective emulsifiers that synergistically perform with BS improving the release and bioaccessibility of bioactive lipids as olive oil.
Assuntos
Ácidos e Sais Biliares , Digestão , Lipólise , Proteínas de Ervilha , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/química , Proteínas de Ervilha/química , Proteínas de Ervilha/metabolismo , Pisum sativum/química , Pisum sativum/metabolismo , Peptídeos/metabolismo , Peptídeos/química , Duodeno/metabolismo , HumanosRESUMO
Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.
Assuntos
Receptor Tirosina Quinase Axl , Doença Celíaca , Duodeno , Peptídeos e Proteínas de Sinalização Intercelular , Mucosa Intestinal , Proteína S , Receptores Proteína Tirosina Quinases , c-Mer Tirosina Quinase , Feminino , Humanos , Masculino , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismo , Doença Celíaca/imunologia , Doença Celíaca/metabolismo , Doença Celíaca/genética , Duodeno/metabolismo , Duodeno/imunologia , Duodeno/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interferons/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Proteína S/metabolismo , Proteína S/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/imunologia , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
AIMS: This study aimed to evaluate the gastroduodenal protective action of crude fraction extracted from P. caribaeorum mucus in Wistar rats. MAIN METHOD: Initially, phytochemical screening was performed to measure secondary metabolites present in the extract. Subsequently, studies of gastroprotective action in Wistar rats were developed. The animals were randomly divided into six experimental groups: SF0.9% group, misoprostol group, and test groups (200, 100, 10, and 1 mg/kg) that received different doses of the crude fraction of zoanthid mucus (CFZM) diluted in SF0.9%. After 14 days of treatment, acute gastric ulcers were induced by gavage by administering aspirin (200 mg/kg). The stomach and duodenum were removed for histopathological and gene analysis of the mucosa. KEY FINDINGS: The present study found that all investigated metabolites showed negative results. The crude fraction showed a gastric and duodenal protective effect evidenced by an increase in the amount and production of mucins (MUC1 and MUC5AC) and mucus production area in the stomach. Histopathological analysis evidenced a decrease in epithelial damage in the duodenum, with a more significant extension of intestinal villi and a greater amount of goblet cells. SIGNIFICANCE: The crude fraction, extracted from P. caribaeorum, showed gastric and duodenal protective action and is not inert in murine gastroduodenal tissues.
Assuntos
Antozoários , Úlcera Gástrica , Ratos , Camundongos , Animais , Ratos Wistar , Mucosa Gástrica , Muco/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Duodeno/metabolismoRESUMO
The intra-amniotic administration approach has been used to evaluate the effects of plant origin prebiotics on intestinal health and on brush border membrane functionality and morphology. Prebiotics are fermentable dietary fibers, which can positively affect the host by selectively stimulating the growth and activity of colon bacteria, thus improving intestinal health. The consumption of prebiotics increases digestive tract motility, which leads to hyperplasia and/or hypertrophy of intestinal cells, increasing nutrient digestive and absorptive surface area. This review collates information about the effects and relationship between prebiotic consumption on small intestinal brush border membrane functionality and morphology by utilizing the intra-amniotic administration approach. To date, research has shown that the intra-amniotic administration of prebiotics affects the expression of key brush border membrane functional proteins, intestinal surface area (villi height/width), and goblet cell number/size. These effects may improve brush border membrane functionality and digestive/absorptive capabilities.
Assuntos
Galinhas , Mucosa Intestinal/efeitos dos fármacos , Microvilosidades/efeitos dos fármacos , Extratos Vegetais/farmacologia , Prebióticos/administração & dosagem , Animais , Colo/microbiologia , Fibras na Dieta/administração & dosagem , Digestão , Duodeno/metabolismo , Duodeno/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Absorção Intestinal , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Microvilosidades/metabolismoRESUMO
The enteric nervous system is responsible for controlling the gastrointestinal tract (GIT) functions. Enteric neuropathies are highly correlated to the development of several intestinal disturbances. Fluoride (F) is extensively applied for dental health improvement and its ingestion can promote systemic toxicity with mild to severe GIT symptomatology and neurotoxicity. Although F harmful effects have been published, there is no information regarding noxiousness of a high acute F exposure (25 mg F/kg) on enteric neurons and levels of expression of intestinal proteins in the duodenum. Quantitative proteomics of the duodenum wall associated to morphometric and quantitative analysis of enteric neurons displayed F effects of a high acute exposure. F-induced myenteric neuroplasticity was characterized by a decrease in the density of nitrergic neurons and morphometric alterations in the general populations of neurons, nitrergic neurons, and substance P varicosities. Proteomics demonstrated F-induced alterations in levels of expression of 356 proteins correlated to striated muscle cell differentiation; generation of precursor metabolites and energy; NADH and glutathione metabolic process and purine ribonucleoside triphosphate biosynthesis. The neurochemical role of several intestinal proteins was discussed specially related to the modulation of enteric neuroplasticity. The results provide a new perspective on cell signaling pathways of gastrointestinal symptomatology promoted by acute F toxicity.
Assuntos
Duodeno/efeitos dos fármacos , Sistema Nervoso Entérico/efeitos dos fármacos , Fluoretos/toxicidade , Neurônios/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteômica/métodos , Animais , Duodeno/metabolismo , Sistema Nervoso Entérico/citologia , Sistema Nervoso Entérico/metabolismo , Masculino , Neurônios/metabolismo , Mapas de Interação de Proteínas/fisiologia , Ratos , Ratos WistarRESUMO
BACKGROUND: Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The Goto-Kakizaki (GK) rat is an experimental model of spontaneous and non-obese T2DM. There is evidence that the intestine contributes to IR development in GK animals. This information prompted us to investigate small intestine remodeling in this animal model. METHODS: Four-month-old male Wistar (control) and GK rats were utilized for the present study. After removing the small intestine, the duodenum, proximal jejunum, and distal ileum were separated. We then measured villi and muscular and mucosa layer histomorphometry, goblet cells abundance, total myenteric and submucosal neuron populations, and inflammatory marker expression in the small intestinal segments and intestinal transit of both groups of animals. KEY RESULTS: We found that the GK rats exhibited decreased intestinal area (p < 0.0001), decreased crypt depth in the duodenum (p = 0.01) and ileum (p < 0.0001), increased crypt depth in the jejunum (p < 0.0001), longer villi in the jejunum and ileum (p < 0.0001), thicker villi in the duodenum (p < 0.01) and ileum (p < 0.0001), thicker muscular layers in the duodenum, jejunum, and ileum (p < 0.0001), increased IL-1ß concentrations in the duodenum and jejunum (p < 0.05), and increased concentrations of NF-κB p65 in the duodenum (p < 0.01), jejunum and ileum (p < 0.05). We observed high IL-1ß reactivity in the muscle layer, myenteric neurons, and glial cells of the experimental group. GK rats also exhibited a significant reduction in submucosal neuron density in the jejunum and ileum, ganglionic hypertrophy in all intestinal segments studied (p < 0.0001), and a slower intestinal transit (about 25%) compared to controls. CONCLUSIONS: The development of IR and T2DM in GK rats is associated with small intestine remodeling that includes marked alterations in small intestine morphology, local inflammation, and reduced intestinal transit.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Trânsito Gastrointestinal , Resistência à Insulina , Intestino Delgado/fisiopatologia , Animais , Glicemia/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Duodeno/inervação , Duodeno/metabolismo , Duodeno/fisiopatologia , Íleo/inervação , Íleo/metabolismo , Íleo/fisiopatologia , Mediadores da Inflamação/metabolismo , Intestino Delgado/inervação , Intestino Delgado/metabolismo , Jejuno/inervação , Jejuno/metabolismo , Jejuno/fisiopatologia , Masculino , Plexo Mientérico/fisiopatologia , Ratos Wistar , Plexo Submucoso/fisiopatologiaRESUMO
This study aimed to provide the performance, localization and expression of the epithelial calcium transporter channels Calbindin-D28k (Calb) and TRPV6, and of the morphology of the digestive and reproductive system of laying quail under heat stress (HS), and with methionine supplementation (MS). This study characterized the positivity (immunohistochemistry) and expression (real-time PCR) of calcium channels in the kidneys, intestine and uterus of 504 laying quails under different MS (100, 110 and 120%) and temperatures (20, 24, 28 and 32°C). The animals under HS (32°C) had lower villus height, villus:crypt ratio, and goblet cell index in the duodenum and jejunum, fewer secondary and tertiary uterine folds, smaller hepatic steatosis, and increased number of distal convoluted renal tubules (CT) positive to Calb, and increased positivity in proximal CTs. Deleterious effects of HS were minimized with MS for: duodenal crypts, number of goblet cells of the jejunum, number of uterine folds, decreased Calb positivity in intestines and kidney, increased positivity of Calb in the uterus and increased TRPV6 gene expression in the kidney (P≤0.05). Epithelial calcium transporters were altered due to less need for calcium absorption and reabsorption due to more calcium available with the MS, increasing egg production in HS and quality in termoneutrality (P≤0.05). MS further increased intestinal villus absorption area and height, increased steatosis, decreased Calb positivity in the intestine and kidney, increased uterine positivity of Calb, and increase Calb and TRPV6 expression in the kidney (P≤0.001) under thermoneutrality. It was concluded that the use of MS (120%) is justifiable in order to partially reverse the deleterious effects of HS on the production, in the epithelial calcium carriers, and in the digestory and reproductive morphology of laying quail.
Assuntos
Proteínas Aviárias/biossíntese , Calbindinas/biossíntese , Duodeno , Regulação da Expressão Gênica/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Fígado , Metionina/farmacologia , Codorniz , Canais de Cátion TRPV/biossíntese , Útero , Animais , Duodeno/anatomia & histologia , Duodeno/metabolismo , Feminino , Fígado/anatomia & histologia , Fígado/metabolismo , Codorniz/anatomia & histologia , Codorniz/metabolismo , Útero/anatomia & histologia , Útero/metabolismoRESUMO
BACKGROUND: Cow's milk protein allergy (CMPA) is the most prevalent food allergy in children, and its pathogenesis remains poorly understood. It has been shown that the combination of genetic predisposition, perinatal factors, and intestinal imbalance of the immune response mediated by cytokines may play an essential role in CMPA pathogenesis. AIM: To characterize the gene expression of Th1, Th2, and Th17 cytokines in the duodenum and rectum in patients with CMPA. METHODS: This is an observational, descriptive, cross-sectional, prospective study. We used specific IgE (ImmunoCAP®) in serum and biopsies from the rectum and duodenum for the detection of cytokine messenger RNA levels by real-time PCR in patients with a positive oral food challenge for CMPA. We analyzed the relative quantification of the gene expression of cytokines by real-time PCR, and we used the housekeeping gene GAPDH for normalization purposes. RESULTS: Thirty children (13 male and 17 female) were evaluated. All patients had an open challenge for CMPA. IgE specific to casein, alfa-lactalbumin, and beta-lactoglobulin was negative in all patients. In terms of cytokine levels, the levels of TNFα, IL-6, IL-12 (Th1), IL-4, IL-10, IL-13 (Th2), and IL-17 were found to be higher in the rectum than in the duodenum (p < 0.05). IL-15 was found to be higher in the duodenum than in the rectum (p < 0.05). CONCLUSIONS: In the present study we observed that the immune response in CMPA seems to be mediated by a Th1, Th2, and Th17 cytokine profile, with the rectum being the main affected site.
Assuntos
Citocinas/metabolismo , Duodeno/metabolismo , Regulação da Expressão Gênica/imunologia , Hipersensibilidade a Leite/imunologia , Proteínas do Leite/imunologia , Reto/metabolismo , Animais , Bovinos , Estudos Transversais , Citocinas/genética , Humanos , Lactente , MasculinoRESUMO
Forty Wistar rats were used: (1) control group (CG); (2) group of periodontal disease (PD); (3) type 1 diabetes mellitus group (T1DM); (4) type 1 diabetes mellitus + periodontal disease group (T1DM + PD). In groups T1DM and T1DM + PD, T1DM induction was performed with the administration of streptozotocin (STZ) 80 mg/kg intraperitoneal body weight. The PD and T1DM + PD groups were submitted to PD induction with ligation. After the experimental phase and euthanasia, histological, radiographic, and morphological analyses were performed. For data analysis, was used the one-way ANOVA and post-test Tukey. The T1DM + PD group had a significantly higher level of fasting blood glucose compared to the other groups. In radiographic and histomorphometric analyses, the T1DM + PD group showed greater alveolar bone loss compared to the control group. The T1DM + PD group showed greater osteoclastic activity compared to the control, T1DM, and PD groups and exhibited an intense inflammatory infiltrate, most of which were PMN, being that the amount of this group of cells (PMN) was significantly greater than the PD group. The heights of the intestinal villi were statistically higher in the PD, T1DM, T1DM + PD groups, compared to the control. Regarding the height of the crypt, only the T1DM and T1DM + PD groups were significantly higher compared to the other groups. Association of diabetes and periodontal inflammation increased the deleterious effects on bone tissue and adverse effect on the permeability of the duodenal mucosa.
Assuntos
Perda do Osso Alveolar/etiologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/patologia , Duodeno/patologia , Mucosa Intestinal/patologia , Doenças Mandibulares/etiologia , Periodontite/patologia , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/patologia , Animais , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Duodeno/metabolismo , Doenças Inflamatórias Intestinais/etiologia , Mucosa Intestinal/metabolismo , Doenças Mandibulares/diagnóstico por imagem , Doenças Mandibulares/patologia , Periodontite/complicações , Periodontite/metabolismo , Permeabilidade , Radiografia , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
This study aims to provide a histological description of different regions of the gastric and duodenal mucosa in Rhesus monkey, as well as to analyze the distribution and the relative frequency of 5-HT. The cardia region mucosa consists of simple columnar epithelium PAS + and AB + and the 5-HT cells were observed at the base of the gland (QA [5-HT cells]/mm²) = 8.72⯱â¯4.98). The body region, has a smaller number of glands. The 5-HT cells were found predominant in the base of the gastric glands. QA= 6.96⯱â¯3.81. When compared to body region, the stomach fundus has smaller gastric pits. The 5-HT cells are found at the base of the glands near the main cells. QA = 5.29⯱â¯2.09. The pylorus region was found to have deep pits and well-developed gastric glands. The 5-HT cells are scarce, at the base of the pyloric gland. QA = 1.18⯱â¯1.36. The duodenum presented goblet cells strong PAS + and AB +. 5-HT cells were found both in the lining epithelium and in the intestinal glands. QA = 8.16⯱â¯2.59.