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1.
Acta Cir Bras ; 35(4): e202000401, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555935

RESUMO

PURPOSE: To evaluate the effect of N-Acetylcysteine (NAC) in newborn rats submitted to hypoxia and reoxygenation (H/R) conditions in an experimental model of necrotizing enterocolitis. METHODS: Eight pregnant rats and their 70 cubs were used (5 groups) and exposed to H/R conditions and received NAC at different times. The animals in the H/R groups were placed in a gas chamber (100% CO2) for 10 minutes and then reoxygenated for 10 minutes (100% O2), twice a day for the first three days of life, with a six-hour span between events. On the third day of life, the animals were anesthetized, laparotomized and the intestines were resected. RESULTS: The H/R and NAC groups showed changes in the intestinal wall in relation to the number, height and width of the villi when compared to the control group (p<0.0001), but with better preservation of structures in the NAC group. There were no differences between groups regarding the number (%) of mitoses. CONCLUSION: The administration of NAC decreased the lesions in the intestinal wall of rats submitted to H/R, therefore suggesting that this drug can be used to prevent the development of necrotizing enterocolitis in newborns.


Assuntos
Acetilcisteína/farmacologia , Enterocolite Necrosante/prevenção & controle , Hipóxia/patologia , Íleo/efeitos dos fármacos , Íleo/patologia , Substâncias Protetoras/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Gravidez , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
2.
Inflamm Bowel Dis ; 26(6): 797-808, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32333601

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage. METHODS: We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples. RESULTS: ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells. CONCLUSIONS: The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD.


Assuntos
Regulação da Expressão Gênica , Imunossupressores/farmacologia , Síndrome do Intestino Irritável/fisiopatologia , Peptidil Dipeptidase A/genética , Serina Endopeptidases/genética , Adolescente , Adulto , Idoso , Animais , Betacoronavirus/metabolismo , Biópsia , Colo/efeitos dos fármacos , Colo/metabolismo , Biologia Computacional , Infecções por Coronavirus/fisiopatologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Imunossupressores/uso terapêutico , Inflamação/fisiopatologia , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma , Adulto Jovem
3.
Eur J Histochem ; 64(1)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32214281

RESUMO

Among oregano properties, its antioxidant and antibacterial effects are particularly interesting. Oregano is also able to induce a higher glycoconjugate production in gut, creating a physical barrier against microorganisms. This study evaluated the effects of adding an aqueous extract of oregano (OAE) to the diet of two homogenous groups of pigs during the finisher phase. The diets were as follows: control commercial diet (CTR group) and CTR diet supplemented (2 g/kg) with OAE (O group). Samples of ileum and caecum from the two groups were examined by conventional histochemistry to analyze complex carbohydrates and by immunohistochemistry to detect Bcl-2 Associate X protein (BAX), an indicator of oxidative stress. Glyco-histochemistry showed significant differences between the two groups. Immunohistochemistry revealed a lower presence of BAX in O group. The OAE supplementation improved the production of glycoconjugates, able to enhance in pig the protection of intestinal mucosa by means of direct and indirect defense actions. The reduced BAX immunostaining observed in O group may be an indicator of enhanced antioxidant action promoted by oregano. The results of this study can be used in further research to identify ways to improve endogenous defence ability, with the aim of reducing antibiotic use and preventing antimicrobial resistance.


Assuntos
Ceco/efeitos dos fármacos , Suplementos Nutricionais , Íleo/efeitos dos fármacos , Origanum/química , Extratos Vegetais/farmacologia , Animais , Anticorpos Monoclonais/imunologia , Glicoconjugados/metabolismo , Imuno-Histoquímica , Camundongos , Suínos , Proteína X Associada a bcl-2/imunologia , Proteína X Associada a bcl-2/metabolismo
4.
BMC Complement Med Ther ; 20(1): 14, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-32020867

RESUMO

BACKGROUND: Euphorbia hirta (Linn) family Euphorbiaceae has been used in indigenous system of medicine for the treatment of gastrointestinal disorders. This study was designed to determine the pharmacological basis for the medicinal use of E. hirta in diarrhea and constipation. METHODS: The aqueous-methanol extract of whole herb of E. hirta (EH.Cr) and its petroleum ether (Pet.EH), chloroform (CHCl3.EH), ethyl acetate (Et.Ac.EH) and aqueous (Aq.EH) fractions were tested in the in-vivo experiments using Balb/c mice, while the in-vitro studies were performed on isolated jejunum and ileum preparations of locally bred rabbit and Sprague Dawley rats, respectively, using PowerLab data system. RESULTS: Qualitative phytochemical analysis showed the presence of alkaloids, saponins, flavonoids, tannins, phenols, cardiac glycosides, while HPLC of EH.Cr showed quercetin in high proportion. In mice, EH.Cr at the dose of 500 and 1000 mg/kg showed 41 and 70% protection from castor oil-induced diarrhea, respectively, similar to the effect of quercetin and loperamide, while at lower doses (50 and 100 mg/kg), it caused an increase in the fecal output. In loperamide-induced constipated mice, EH.Cr also displayed laxative effect with respective values of 28.6 and 35.3% at 50 and 100 mg/kg. In rabbit jejunum, EH.Cr showed atropine-sensitive inhibitory effect in a concentration-dependent manner, while quercetin and nifedipine exhibited atropine-insensitive effects. Fractions of E. hirta also produced atropine-sensitive inhibitory effects except Pet.EH and CHCl3.EH. On high (80 mM) and low (20 mM) K+ - induced contractions, the crude extract and fractions exhibited a concentration-dependent non-specific inhibition of both spasmogens and displaced concentration-response curves of Ca++ to the right with suppression of the maximum effect similar to the effect quercetin and nifedipine. Fractions showed wide distribution of spasmolytic and Ca++ antagonist like effects. In rat ileum, EH.Cr and its fractions exhibited atropine-sensitive gut stimulant effects except Pet.EH. CONCLUSION: The crude extract of E. hirta possesses antidiarrheal effect possibly mediated through Ca++ antagonist like gut inhibitory constituents, while its laxative effect was mediated primarily through muscarinic receptor agonist like gut stimulant constituents. Thus, these findings provide an evidence to the folkloric use of E. hirta in diarrhea and constipation.


Assuntos
Cálcio/metabolismo , Constipação Intestinal/tratamento farmacológico , Diarreia/tratamento farmacológico , Euphorbia/química , Extratos Vegetais/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Cromatografia Líquida , Modelos Animais de Doenças , Feminino , Íleo/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Paquistão , Coelhos , Ratos , Ratos Sprague-Dawley
5.
Orv Hetil ; 160(49): 1927-1934, 2019 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-31786941

RESUMO

Glucagon-like peptide-1 (GLP1) and their receptor agonists - beside their blood glucose lowering and central effects- affect also the gastrointestinal function in many respects. They slow down the stomach emptying, the motility of the small bowel and colon - this is the explanation for the "ileal brake" terminology -, stimulate the function of exocrine pancreatic acinar cells and increase amylase production. GLP1 receptor agonists belong to the defining tools of the blood glucose lowering therapy in type 2 diabetes. Their long- and short-acting derivatives have different influence on the fasting and the postprandial blood glucose, respectively. By introducing the term non-prandial and prandial type analogues - which seems to be forced in light of the newer data - the potential slowdown in gastric emptying is the center of interest, lately, however, especially in the case of long-acting GLP1 variants, at least such attention should be paid to controlling bowel function. The article reviews the physiological effects of GLP1 on the gastrointestinal tract and draws attention to the potential for the prevention of possible side effects through detailed patient information and dietary advises. Orv Hetil. 2019; 160(49): 1927-1934.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/farmacologia , Íleo/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Íleo/metabolismo , Intestino Delgado/metabolismo , Período Pós-Prandial/efeitos dos fármacos
6.
J Agric Food Chem ; 67(49): 13737-13750, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31789024

RESUMO

Genistein is abundant in animal feed. In this study, the side effects of high-dose genistein on intestinal health and hypothalamic RNA profile were evaluated. Chicks exposed to high-dose genistein by intraperitoneal injection (416 ± 21, 34.5 ± 2.5) and feed supplementation (308 ± 19, 27.2 ± 2.1) both showed a reduced body weight gain and feed intake in comparison with the control group (261 ± 16, 22.7 ± 1.6, P < 0.01). In comparison with the control (22.4 ± 0.5, 33.3 ± 2.4), serum levels of albumin and total protein were decreased after high-dose genistein injection (21.6 ± 0.5, 31.8 ± 1.6) and diet supplementation (20.6 ± 0.9, 29.9 ± 2.5, P < 0.001). Interestingly, the genistein diet presented the chick hypothalamus with downregulated expression of bitter receptors (TAS1R3, P < 0.05). Meanwhile, it upregulated the expressions of TAS2R1 (P < 0.05) and downstream genes (PLCB2 and IP3R3) in the ileum (P < 0.05). Accordingly, high-dose dietary genistein reduced villus height and the abundance of Lactobacillus, along with the increased abundance of pathogenic bacteria in the ileum (P < 0.05). Furthermore, transcriptomic analysis identified 348 differently expressed genes (168 upregulated and 224 downregulated) in the high-dose dietary genistein treated group in comparison with the control (P < 0.05, |log2FoldChange| > 0.585). Therefore, high-dose dietary genistein altered the hypothalamic RNA profile and signal processing. Cluster analysis further revealed that high-dose dietary genistein significantly influenced apoptosis, the immune process, and the whole synthesis of steroid hormones in the hypothalamus (P < 0.05). In conclusion, high-dose dietary genistein altered the hypothalamic RNA profile and intestinal health of female chicks.


Assuntos
Galinhas/metabolismo , Suplementos Nutricionais/efeitos adversos , Genisteína/efeitos adversos , Hipotálamo/metabolismo , RNA/genética , Ração Animal/efeitos adversos , Ração Animal/análise , Animais , Peso Corporal/efeitos dos fármacos , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Genisteína/análise , Hipotálamo/efeitos dos fármacos , Íleo/efeitos dos fármacos , Íleo/metabolismo , RNA/metabolismo , Esteroides/metabolismo
7.
Nat Commun ; 10(1): 4971, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672964

RESUMO

Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.


Assuntos
Ácidos e Sais Biliares/metabolismo , Catequina/análogos & derivados , Alimentos e Bebidas Fermentados , Microbioma Gastrointestinal/efeitos dos fármacos , Hipercolesterolemia/metabolismo , Chá , Adulto , Amidoidrolases/metabolismo , Animais , Catequina/farmacologia , Ácido Quenodesoxicólico/metabolismo , Colesterol/metabolismo , Dieta Hiperlipídica , Transplante de Microbiota Fecal , Fatores de Crescimento de Fibroblastos/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/metabolismo , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metabolômica , Camundongos , Extratos Vegetais/farmacologia , RNA Ribossômico 16S , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais , Adulto Jovem
8.
BMC Complement Altern Med ; 19(1): 307, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711473

RESUMO

BACKGROUND: Asphodelus tenuifolius Cav. (Asphodelaceae) has traditional reputability in treatment of diarrhea and constipation but no scientific study has been reported for its gastrointestinal effects. Present study was conducted to evaluate antidiarrheal and laxative activities of the plant. METHODS: Aqueous-ethanol crude extract of Asphodelus tenuifolius (At.Cr) was subjected to phytochemical screening and liquid-liquid fractionation. In vivo studies of charcoal meal intestinal transit test, antidiarrheal activity against castor oil induced diarrhea and laxative activity were performed in mice. In vitro experiments were conducted upon rabbit jejunum preparations using standard tissue bath techniques. RESULTS: Phytochemical screening indicated presence of alkaloids, anthraquinones, flavonoids, saponins, steroids, tannins and phenols in At.Cr. In charcoal meal intestinal transit test, At.Cr increased (p < 0.001) intestinal motility at 100 mg/kg dose, but decreased (p < 0.001) it at 500 mg/kg dose, when compared to the control group. At.Cr (300-700 mg/kg) provided protection from castor oil induced diarrhea in mice, which was significant (p < 0.001) at 500 and 700 mg/kg doses, as compared to the saline treated control group. At.Cr (50 and 100 mg/kg) enhanced total and wet feces counts in normal mice, as compared to saline treated control. In jejunum preparations, At.Cr inhibited spontaneous, K+ (80 mM) and K+ (25 mM) mediated contractions, similar to verapamil. Pre-incubation of jejunum preparations with At.Cr resulted in rightward nonparallel shift in Ca+ 2 concentration response curves, similar to verapamil. The spasmolytic activity was concentrated in ethylacetate fraction. Aqueous fraction exhibited spasmogenicity upon spontaneous contractions, which was blocked in presence of verapamil, but remained unaffected by other tested antagonists. CONCLUSION: The Asphodelus tenuifolius crude extract possesses gut modulatory activity, which may normalize gut functions in diarrhea and constipation. The spasmolytic activity of the extract was found to be mediated through Ca+ 2 channel blocking action. The spasmogenic activity, found partitioned in aqueous fraction, possibly involves Ca+ 2 influx through voltage gated Ca+ 2 channels. The study supports ethnic uses of the plant in diarrhea and constipation.


Assuntos
Antidiarreicos/administração & dosagem , Asparagales/química , Constipação Intestinal/tratamento farmacológico , Diarreia/tratamento farmacológico , Laxantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Antidiarreicos/química , Antidiarreicos/isolamento & purificação , Constipação Intestinal/fisiopatologia , Diarreia/fisiopatologia , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Íleo/efeitos dos fármacos , Íleo/fisiopatologia , Laxantes/química , Laxantes/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Coelhos
9.
Biomed Pharmacother ; 118: 109393, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545258

RESUMO

OBJECTIVE: Diabetes mellitus is associated with gut microbiota disturbance and intestinal mucosal injuries. This study investigated the influence of propolis on the gut microbiota and intestinal mucosa in rats with diabetes. METHODS: Sprague-Dawley (SD) rats were randomly assigned to the control group, model group, and three propolis groups (supplemented with 80, 160, and 240 mg/kg·bw propolis, respectively). A high-fat diet combined with a streptozotocin (STZ) abdominal injection were used to induce diabetes in the rats. After 4 weeks, the intestinal histopathological analysis of the ileum was observed by transmission electron microscopy. The fasting blood glucose (FBG), plasma insulin, glucose tolerance (OGTT) and glycosylated hemoglobin (HbA1c) levels were measured. The expression of tight junction (TJ) proteins in the ileum was measured using western blotting. The molecular ecology of the fecal gut microbiota was analyzed by 16S rDNA high-throughput sequencing. The contents of the short-chain fatty acids (SCFAs) in feces were measured using high-performance liquid chromatography (HPLC). RESULTS: After propolis treatment, compared to the model group, FBG and HbA1c levels declined, while the glucose tolerance and insulin sensitivity index (ISI) increased. The levels of TJ proteins in the ileum increased in the propolis groups. The tight junctions and gap junctions of the intestinal epithelium were also improved in the propolis groups. The contents of the feces acetic acid, propionic acid and butyrate were increased in the propolis groups. 16S rDNA high-throughput sequencing revealed that the composition of the gut microbiota of rats in the propolis supplement group was significantly improved. CONCLUSIONS: Compared to the model group, propolis exerted hypoglycemic effects in diabetic rats, and it repaired intestinal mucosal damage, benefited the communities of the gut microbiota and increased SCFA levels in diabetic rats.


Assuntos
Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Experimental/fisiopatologia , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiopatologia , Própole/farmacologia , Animais , Biodiversidade , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Jejum/sangue , Ácidos Graxos/metabolismo , Fezes/química , Íleo/efeitos dos fármacos , Íleo/patologia , Íleo/ultraestrutura , Insulina/sangue , Mucosa Intestinal/efeitos dos fármacos , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Filogenia , Ratos Sprague-Dawley
10.
Pharm Biol ; 57(1): 595-603, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31496325

RESUMO

Context: Oxymatrine (OMT) has various pharmacological effects, including immune reaction regulation, anti-inflammation and anti-hypersensitive reaction. Objective: This is the first report to investigate the molecular mechanism of OMT function in l-arginine (Arg)-induced acute pancreatitis (AP) involving intestinal injury. Materials and methods: Rat pancreatic AR42J and small intestinal IEC-6 cells were treated with Arg (200-800 µM) for 48 h plus OMT (4 mg/mL) treatment. Thirty adult Wistar rats were randomly assigned to control (saline), AP (i.p. of 250 mg/100 g body weight Arg) and OMT (i.p. injection of 50 mg/kg b.w. OMT every 6 h following Arg). Both cells and rats were harvested at 48 h. Results: Arg-induced cell proliferation in both rats AR42J (EC50 633.9 ± 31.4 µM) and IEC-6 cells (EC50 571.3 ± 40.4 µM) in a dose-dependent manner, which was significantly inhibited by OMT (4 mg/mL). Meanwhile, Arg (600 µM) induced expression of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, NF-κB, IL-17A/IL-17F and IFN-γ) and activation of p-p38/p-ERK in vitro, which was reversed by OMT. In vivo, OMT (50 mg/kg) inhibited 250 mg/100 g of Arg-induced AP involving intestinal injury, including inhibiting Arg-induced inflammatory in pancreas and intestine, inhibiting Arg-induced increase of TNF-α, IL-6, IL-1ß, NF-κB and p-p38/p-ERK-MAPK signalling, and inhibiting Arg-induced increase of IL-17A/IL-17F, IFN-γ, ROR-γt and T-bet. Meanwhile, OMT inhibited Arg-induced expression of CD44 and CD55 in intestinal injury. Discussion and conclusions: OMT protects against Arg-induced AP involving intestinal injury via regulating Th1/Th17 cytokines and MAPK/NF-κB signalling, which is a promising therapeutic agent in clinics.


Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Íleo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Pancreatite/prevenção & controle , Quinolizinas/farmacologia , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Doença Aguda , Animais , Arginina , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas/imunologia , Modelos Animais de Doenças , Íleo/imunologia , Íleo/patologia , Masculino , Pancreatite/imunologia , Pancreatite/patologia , Ratos Wistar , Células Th1/imunologia , Células Th17/imunologia
11.
Poult Sci ; 98(12): 6897-6902, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376356

RESUMO

Poultry meats can become contaminated with pathogenic bacteria through digesta leakage during processing. Reducing the bacteria load in digesta of market-aged broilers prior to processing reduces the incidence of fecal contamination at the processing plant. A lysozyme product was incorporated in a maltodextrin-based feed offered during the pre-shipping feed withdrawal period to reduce bacteria in ileal contents of market-aged broilers. Twenty 36-day-old broilers were randomly allocated to each of 16 pens. For a 9 h period each pen was randomly assigned to one of the following treatments: no feed, maltodextrin-based feed with a lysozyme product (Inovapure) added at 0, 10, or 20 g per kg of feed. Feed consumption was determined and a minimum of 3 birds were randomly selected from each pen and euthanized. The ileal contents were removed and weighed. Samples were analyzed for Clostridium perfringens, aerobic bacteria, Enterobacteriaceae, E. coli, and coliform numbers using standard culturing techniques and next generation sequencing was performed to determine population shifts. Bacteria counts were transformed to log10 colony forming units (cfu) and analyzed as a completely randomized design. The data from next generation sequencing was analyzed as a 3 × 5 factorial design using Proc Mixed of SAS. Lysozyme did not affect feed consumption nor were the weight of ileal contents different for birds fed maltodextrin-based feeds compared to birds on traditional feed withdrawal. E. coli/coliforms and Enterobacteriaceae plates had no signs of bacterial growth. The number of Clostridium perfringens and aerobic bacteria in the ileal contents of market-aged broilers was not different between treatments using the traditional culturing techniques. Next generation sequencing was a useful alternative to traditional culture techniques as results revealed that bacilli were reduced and clostridia increased for the 20 g lysozyme treatment. Addition of lysozyme to a maltodextrin based feed did not change overall numbers of bacteria but was effective in altering the participants in the bacteria community in ileal contents of market-aged broilers.


Assuntos
Galinhas/microbiologia , Íleo/microbiologia , Muramidase/metabolismo , Polissacarídeos/metabolismo , Ração Animal/análise , Animais , Galinhas/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Íleo/efeitos dos fármacos , Masculino , Muramidase/administração & dosagem , Polissacarídeos/administração & dosagem , Distribuição Aleatória
12.
Bratisl Lek Listy ; 120(8): 576-580, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379180

RESUMO

AIM: Quinine, a frequently used anti-malaria alkaloid isolated from the Cinchona bark, possesses numerous toxic properties, the majority of which arrive from a dysfunction of the gastrointestinal tract. Similarly, cinchonine, another alkaloid from the Cinchona bark, displays a great potential for treating malaria (especially the resistant forms). METHODS: In this work, we aimed to evaluate the effects of cinchonine on spontaneous and induced Wistar rat ileum contractions in order to uncover potential side effects that might arise after its application. RESULTS: Cinchonine produced a concentration-dependent spasmolytic activity, which was found to be reversible (i.e. disappeared after tissue wash-up), with an IC50 value of 273 µM. Furthermore, the mechanism of action of cinchonine at IC50 elucidated through experiments with acetylcholine and Ca2+-induced ileum contractions. The applied IC50 concentration of cinchonine statistically significantly prevented the occurrence of contractions after the application of specific agonist. The obtained results are in a range with the effects seen with standard receptor antagonists, i.e. atropine and verapamil. CONCLUSIONS: The obtained results showed that cinchonine inhibited both types of induced contractions, suggesting a Ca2+-channels mediated modus operandi (Fig. 4, Ref. 19).


Assuntos
Alcaloides/farmacologia , Alcaloides de Cinchona/farmacologia , Cinchona/química , Íleo/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Parassimpatolíticos/farmacologia , Animais , Ratos , Ratos Wistar
13.
J Med Food ; 22(8): 789-796, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31329014

RESUMO

Royal jelly (RJ) is widely used as a cosmetic or dietary supplement to relieve various health disorders, such as dry skin, fatigue, and menopause. RJ has been recommended to improve constipation on a commercial basis. However, the detailed mechanisms by which RJ influences intestinal motility and whether RJ improves constipation remain unclear. Therefore, we investigated the effects of RJ on the motility of mouse ileum both in vitro and in vivo. Using myograph methods, RJ dose-dependently induced contractions of isolated ileal segments, which were inhibited by treatment with atropine. Eserine sulfate, a cholinesterase inhibitor, enhanced the RJ-induced contractions, whereas RJ treated with acetylcholinesterase did not result in ileum contraction. RJ-induced contractions were not affected by NG-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, although nicotine-induced contractions were significantly enhanced. In contrast, in a gastrointestinal (GI) transit model, single oral administration of 300 mg/kg RJ did not affect GI transit in both normal mice and the loperamide-induced constipation model mice. These results demonstrate that acetylcholine in RJ directly acted on the muscarinic receptors of the mouse intestinal smooth muscle, causing it to contract in vitro. In contrast, single oral administration of RJ did not improve constipation. This study is the first to evaluate the effects of RJ on the motility of mouse ileum in in vitro and in vivo experiments for the validation of application of RJ as a gentle laxative.


Assuntos
Ácidos Graxos/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Íleo/fisiopatologia , Acetilcolina/metabolismo , Animais , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Técnicas In Vitro , Laxantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR
14.
Pharmacology ; 104(3-4): 207-211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31302651

RESUMO

The effects of cinnamaldehyde (CNA), known as a transient receptor potential ankyrin 1 (TRPA1) agonist, on guinea-pig ileum and urinary bladder were studied in isolated organ experiments. Contractile effects were found to be present on both preparations. In the ileum, both cholinergic and purinergic (pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt-sensitive) mechanisms are involved; the TRPA1 antagonist A967079 (1 µmol/L) significantly reduced the response. The contractile response to CNA in the bladder, but not in the ileum, was significantly reduced by in vitro capsaicin desensitization. In the bladder A967079 or the TRPV1 antagonist, BCTC failed to reduce the response. A direct relaxation on the smooth muscle was detected in the precontracted ileum. In the precontracted urinary bladder, CNA also caused relaxation that was insensitive to capsaicin pretreatment. It is suggested that CNA excites the muscles of the bladder via activation of capsaicin-sensitive nerves; in the ileum, it may interact with TRPA1 located on tissue elements that initiate both purinergic and cholinergic mechanisms. The relaxant effects of CNA may be due to the direct inhibition of the smooth muscles.


Assuntos
Acroleína/análogos & derivados , Músculo Liso/efeitos dos fármacos , Acroleína/farmacologia , Animais , Capsaicina/metabolismo , Feminino , Cobaias , Íleo/efeitos dos fármacos , Íleo/metabolismo , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Canais de Cátion TRPV/metabolismo , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo
15.
Food Chem Toxicol ; 132: 110673, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302221

RESUMO

The present study was designed to assess the influence of acrylamide supplementation, in tolerable daily intake (TDI) dose and a dose ten times higher than TDI, on the neurochemical phenotype of the ENS neurons and synthesis of proinflammatory cytokines in the wall of the porcine ileum. The study was performed on 15 juvenile female Danish Landrace pigs, divided into three groups: C group- animals receiving empty gelatine capsules, LD group- animals receiving capsules with the TDI dose (0.5 µg/kg b.w./day) of acrylamide and HD group- animals receiving acrylamide in a dose ten times higher than the TDI (5 µg/kg b.w./day) in a morning meal for 28 days. It was established that supplementation of acrylamide led to an increase in substance P (SP)-, calcitonin gene-related peptide (CGRP)-, galanin (GAL)- and vesicular acetylcholine transporter (VAChT)-like immunoreactive (LI) neurons as well as a decrease in neuronal nitric oxide synthase (nNOS) -like immunoreactivity in all types of ileum intramural plexuses. Moreover, using ELISA method, an increase in the level of proinflammatory cytokines (IL-1ß, IL-6 and TNF- α) was noted in the ileum wall. The results suggest that SP, CGRP, GAL, nNOS and VACHT participate in the regulation of inflammatory conditions induced by acrylamide supplementation.


Assuntos
Acrilamida/administração & dosagem , Íleo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Acrilamida/farmacologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Galanina/metabolismo , Íleo/patologia , Mediadores da Inflamação/metabolismo , Neurônios/enzimologia , Neurônios/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Substância P/metabolismo , Suínos , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismo
16.
Food Funct ; 10(6): 3535-3542, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31149689

RESUMO

Enteric infection is a major cause of morbidity and mortality in both humans and animals worldwide. Immunotherapy against intestinal infection is a well-known alternative to the antibiotic strategy. Herein, we demonstrated that isoleucine significantly suppressed the multiplication of E. coli in the presence of IPEC-J2 cells. Isoleucine supplementation enhanced the concentrations of total plasma protein and IgA in pigs compared to the alanine control diet, while inhibiting the increase in plasma endotoxin and IL-6 contents induced by E. coli challenge. A significant interaction between the E. coli challenge and the diet treatment was found in the red blood cell volume. Isoleucine improved the expression of porcine ß-defensin-1 (pBD-1), pBD-2, pBD-3, pBD-114 and pBD-129 in the jejunum and ileum of pigs with or without E. coli challenge. Conclusively, isoleucine attenuated the infection caused by the E. coli challenge possibly through increasing the intestinal ß-defensin expression and inhibiting the increase in plasma endotoxin and IL-6 in weaned pigs.


Assuntos
Defensinas/genética , Endotoxinas/sangue , Infecções por Escherichia coli/veterinária , Escherichia coli/fisiologia , Interleucina-6/sangue , Mucosa Intestinal/metabolismo , Isoleucina/administração & dosagem , Doenças dos Suínos/tratamento farmacológico , Animais , Defensinas/metabolismo , Suplementos Nutricionais/análise , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Íleo/efeitos dos fármacos , Íleo/metabolismo , Íleo/microbiologia , Interleucina-6/genética , Mucosa Intestinal/microbiologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/microbiologia , Suínos , Doenças dos Suínos/genética , Doenças dos Suínos/metabolismo , Doenças dos Suínos/microbiologia
17.
J Ethnopharmacol ; 241: 112014, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31181315

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Butea monosperma (Lam.) Taub. (family Leguminosae), popularly known as 'Palash' possess numerous medicinal properties since ancient times. According to the Wealth of India, stem bark of this plant exhibits various therapeutic properties like antimicrobial, astringent, styptic, aphrodisiac, and anti-inflammatory. AIM OF THE STUDY: The purpose of the present study was to investigate antibacterial and antidiarrheal effect of B. monosperma bark against newly isolated gram negative pathogenic bacterial strain Enterobacter cloacae. MATERIALS AND METHODS: Aqueous extract of B. monosperma bark (BMAqE) was subjected to LC-MS/MS analysis for determination of bioactive components. Antibacterial study of BMAqE was assessed using bacterial growth kinetic study, fluorescence spectroscopy, outer and inner membrane permeability assay, dehydrogenase inhibitory assay and protein leakage assay followed by field emission scanning electron microscope (FE-SEM) study. Antidiarrheal activity was studied using castor oil induced diarrhea model in albino rats followed by histopathology studies of rat ileum. RESULTS: LC-MS/MS analysis of BMAqE revealed presence of twenty-two different active phytoconstituents out of which most of the constituents belong to flavonoid and polyphenol family. BMAqE showed MIC and MBC (IC90) value of 5 and 200 µg/mL against targeted bacterial strain. BMAqE exhibited potent and dose dependent bactericidal effect via disruption of integrity of bacterial cell membrane, enzymatic degradation, leakage of intracellular protein and ruptured bacterial cell. In castor oil induced diarrhea model, BMAqE (200 mg/kg; orally) caused marked reduction (75.66%) in the frequency of defecation and mean weight of faeces (0.54 ±â€¯0.04) when compared to control group (2.26 ±â€¯0.25). Histopathology study revealed marked restoration of cellular architecture of rat ileum tissue. Four known flavonoids were isolated from BMAqE using column chromatography. In ex-vivo study, BMAqE (0.0002, 0.0004 and 0.0006 g/L) and isolated flavonoids i.e. rhamnetin, quercetin, kaempferol and catechin (0.5, 5 & 50 µm) produced a significant (p < 0.001) change in EC50 and indicated competitive phenomena via rightward shift of acetylcholine CRC with pA2 of 3.78, 8.0, 7.1, 7.0 and 6.9 respectively. CONCLUSION: BMAqE exhibits impressive antibacterial and anti-diarrheal activity and can be effectively used to eradicate water borne diseases.


Assuntos
Antibacterianos/farmacologia , Antidiarreicos/farmacologia , Butea , Enterobacter cloacae/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Enterobacter cloacae/crescimento & desenvolvimento , Feminino , Íleo/efeitos dos fármacos , Íleo/patologia , Íleo/fisiologia , Masculino , Compostos Fitoquímicos/farmacologia , Casca de Planta , Ratos Wistar
18.
Biomed Pharmacother ; 116: 109040, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31170664

RESUMO

Intestinal pathophysiological alterations have recently been revealed to be implicated in the pathogenesis of hypertension, necessitating further investigations to better understand the intestinal effects of anti-hypertensive drugs. The current study thus investigated the pharmacological implications of a commonly used first-line angiotensin II type 1 receptor blocker, candesartan cilexetil, on the intestinal barrier impairment and gut dysbiosis in spontaneously hypertensive rats (SHRs). The results revealed that candesartan treatment protected against ileal and colonic pathologies and increased the intestinal expression of genes encoding tight junction proteins such as cingulin, occludin and tight junction protein 1 in SHRs. Serum level of lipopolysaccharides-binding protein was increased in candesartan-treated SHRs, supporting the notion that candesartan treatment provided protection against hypertension-associated impairment of intestinal barrier. Candesartan treatment also increased the amount of fecal short-chain fatty acids (SCFAs) including acetic acid, propionic acid, and butyric acid in SHRs. Fecal 16S rDNA sequencing further revealed that candesartan treatment normalized hypertension-altered ratio of Firmicutes to Bacteroidetes in SHRs. Most notably, candesartan treatment counteracted hypertension-associated diminishment of lactic acid-producing genus Lactobacillus. Taken together, the current study demonstrates for the first time that candesartan treatment alleviates hypertension-associated pathophysiological alterations in the gut, increases microbial production of SCFAs and preserves gut Lactobacillus under hypertensive conditions, which sheds novel light on the pharmacological implications of candesartan in the treatment of hypertension.


Assuntos
Benzimidazóis/uso terapêutico , Trato Gastrointestinal/fisiopatologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Tetrazóis/uso terapêutico , Animais , Benzimidazóis/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Colo/fisiopatologia , Ácidos Graxos/metabolismo , Fezes/química , Fibrose , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Íleo/efeitos dos fármacos , Íleo/patologia , Íleo/fisiopatologia , Lactobacillus/efeitos dos fármacos , Masculino , Permeabilidade , Ratos Endogâmicos SHR , Tetrazóis/farmacologia
19.
Pharmacol Res ; 146: 104323, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31229561

RESUMO

Calcium-activated chloride channels (CaCCs)/TMEM16A control diverse fundamental physiological functions, and abnormal function of TMEM16A will lead to various diseases including asthma, hypertension, gastrointestinal hypomotility and cancers. Therefore, TMEM16A as drug targets for related diseases has been increasingly concerned by researchers. In this work, COS were reported as novel natural activators of TMEM16A. It was demonstrated that COS can activate TMEM16A in a concentration dependent manner, with an EC50 of 74.5 µg/mL. Then, fluorescence experiments and inside-out patch clamp experiments were combined to confirm that COS can directly activate TMEM16A. Further, we compared the activation effects of COS monomers DP2 to DP6, with DP3 the best activator. Molecular simulation was performed to find that the binding sites between DP3 and TMEM16A are E143 and E146 in TMEM16A, and it was speculated that COS and TMEM16A may be combined by electrostatic interaction. Finally, we verified that guinea pig ileum contraction was promoted by COS and the monomers through activating TMEM16A. Collectively, COS are novel efficient natural activators of TMEM16A, with potential to be developed to treatment diseases caused by down-regulation of TMEM16A including gastrointestinal hypomotility.


Assuntos
Anoctamina-1/metabolismo , Quitosana/química , Quitosana/farmacologia , Canais de Cloreto/metabolismo , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Animais , Sítios de Ligação/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular , Cobaias , Células HEK293 , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Camundongos , Proteínas de Neoplasias/metabolismo
20.
World J Gastroenterol ; 25(23): 2924-2934, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31249450

RESUMO

BACKGROUND: The digestive tract is the maximal immunizing tissue in the body, and mucosal integrity and functional status of the gut is very important to maintain a healthy organism. Severe infection is one of the most common causes of gastrointestinal dysfunction, and the pathogenesis is closely related to endotoxemia and intestinal barrier injury. Bifidobacterium is one of the main probiotics in the human body that is involved in digestion, absorption, metabolism, nutrition, and immunity. Bifidobacterium plays an important role in maintaining the intestinal mucosal barrier integrity. This study investigated the protective mechanism of Bifidobacterium during ileal injury in rats. AIM: To investigate the effects of Bifidobacterium on cytokine-induced neutrophil chemoattractant (CINC) and insulin-like growth factor 1 (IGF-1) in the ileum of rats with endotoxin injury. METHODS: Preweaning rats were randomly divided into three groups: Control (group C), model (group E) and treatment (group T). Group E was intraperitoneally injected with lipopolysaccharide (LPS) to create an animal model of intestinal injury. Group T was intragastrically administered Bifidobacterium suspension 7 d before LPS. Group C was intraperitoneally injected with normal saline. The rats were killed at 2, 6 or 12 h after LPS or physiological saline injection to collect ileal tissue samples. The expression of ileal CINC mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), and expression of ileal IGF-1 protein and mRNA was detected by immunohistochemistry and RT-PCR, respectively. RESULTS: The ileum of rats in Group C did not express CINC mRNA, ileums from Group E expressed high levels, which was then significantly decreased in Group T (F = 23.947, P < 0.05). There was no significant difference in CINC mRNA expression at different times (F = 0.665, P > 0.05). There was a high level of IGF-1 brown granules in ileal crypts and epithelial cells in Group C, sparse staining in Group E, and dark, dense brown staining in Group T. There was a significant difference between Groups C and E and Groups E and T (P < 0.05). There was no significant difference in IGF-1 protein expression at different times (F = 1.269, P > 0.05). IGF-1 mRNA expression was significantly different among the three groups (P < 0.05), though not at different times (F = 0.086, P > 0.05). CONCLUSION: Expression of CINC mRNA increased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium reduced CINC mRNA expression. IGF-1 protein and mRNA expression decreased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium prevented the decrease in IGF-1 expression. Bifidobacterium may increase IGF-1 expression and enhance intestinal immune barrier function in rats with endotoxin injury.


Assuntos
Bifidobacterium longum subspecies infantis , Quimiocina CXCL1/metabolismo , Ileíte/terapia , Fator de Crescimento Insulin-Like I/metabolismo , Probióticos/administração & dosagem , Animais , Quimiocina CXCL1/imunologia , Modelos Animais de Doenças , Endotoxinas/toxicidade , Humanos , Ileíte/induzido quimicamente , Ileíte/patologia , Íleo/efeitos dos fármacos , Íleo/imunologia , Íleo/patologia , Fator de Crescimento Insulin-Like I/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar
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