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1.
J Agric Food Chem ; 68(1): 160-167, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31825618

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of intestinal mucosa and submucosa, characterized by the disruption of the intestinal epithelial barrier, increased production of inflammatory mediators, and excessive tissue injury. Intestinal epithelial cells, as well as microvascular endothelial cells, play important roles in IBD. To study the potential effects of kaempferol in IBD progress, we established a novel epithelial-endothelial cells coculture model to investigate the intestinal inflammation and barrier function. Data demonstrated an obvious increased transepithelial electrical resistance (TEER) (1222 ± 60.40 Ω cm2 vs 1371 ± 38.77 Ω cm2), decreased flux of FITC (180.8 ± 20.06 µg/mL vs 136.7 ± 14.78 µg/mL), and up-regulated occludin and claudin-2 expression in Caco-2 that was specifically cocultured with endothelial cells. Meanwhile, 80 µM kaempferol alleviated the drop of TEER, the increase of FITC flux, and the overexpression of interleukin-8 (IL-8) induced by 1 µg/mL lipopolysaccharide (LPS). Additionally, kaempferol also ameliorated the LPS-induced decrease of protein expression of zonula occludens-1 (ZO-1), occludin, and claudin-2, together with the inhibited protein expressions of the phosphorylation level of NF-κB and I-κB induced by LPS. Our results suggest that kaempferol alleviates the IL-8 secretion and barrier dysfunction of the Caco-2 monolayer in the LPS-induced epithelial-endothelial coculture model via inhibiting the NF-κB signaling pathway activation.


Assuntos
Células Endoteliais/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Mucosa Intestinal/citologia , Quempferóis/farmacologia , Lipopolissacarídeos/efeitos adversos , Células CACO-2 , Claudina-2/genética , Claudina-2/metabolismo , Técnicas de Cocultura , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/imunologia , Microvilosidades/efeitos dos fármacos , Microvilosidades/genética , Microvilosidades/metabolismo , Ocludina/genética , Ocludina/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
2.
J Agric Food Chem ; 68(2): 441-450, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31736308

RESUMO

Absorption of glucose, via intestinal Na+/glucose cotransporter 1 (SGLT1), activates salt and water absorption and is an effective route for treating Escherichia coli (E. coli)-induced diarrhea. Activity and expression of SGLT1 is regulated by sensing of sugars and artificial/natural sweeteners by the intestinal sweet receptor T1R2-T1R3 expressed in enteroendocrine cells. Diarrhea, caused by the bacterial pathogen E. coli, is the most common post-weaning clinical feature in rabbits, leading to mortality. We demonstrate here that, in rabbits with experimentally E. coli-induced diarrhea, inclusion of a supplement containing stevia leaf extract (SL) in the feed decreases cumulative morbidity, improving clinical signs of disease (p < 0.01). We show that the rabbit intestine expresses T1R2-T1R3. Furthermore, intake of SL enhances activity and expression of SGLT1 and the intestinal capacity to absorb glucose (1.8-fold increase, p < 0.05). Thus, a natural plant extract sweetener can act as an effective feed additive for lessening the negative impact of enteric diseases in animals.


Assuntos
Diarreia/veterinária , Células Enteroendócrinas/metabolismo , Infecções por Escherichia coli/veterinária , Escherichia coli/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Adoçantes não Calóricos/administração & dosagem , Extratos Vegetais/administração & dosagem , Coelhos/microbiologia , Transportador 1 de Glucose-Sódio/metabolismo , Stevia/química , Animais , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Diarreia/mortalidade , Células Enteroendócrinas/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/mortalidade , Feminino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Folhas de Planta/química , Coelhos/metabolismo , Transportador 1 de Glucose-Sódio/genética
3.
Arch Microbiol ; 202(1): 161-169, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31549206

RESUMO

Many kinds of antibiotics have effects on intestinal structure and function. In the current experimental study, we evaluate the effect of oral florfenicol on intestinal barrier in mice. Thirty adult male mice were randomly divided into two groups, the group none (N) and the group florfenicol (F), the mice in group F were orally administered florfenicol 100 mg/kg body weight (BW) for 7 days. At day 8, mice were euthanized and sampled for the analysis of alterations in genes and proteins from jejunum, jejunum morphology and microbiota analysis. Administration of florfenicol caused higher liver index (P < 0.05). In the jejunum, mucosa injury and villus rupture, compared with the group N, the villus length and V/C (villus length/crypt depth) in group F were marked decrease (P < 0.01). The transcription level of Muc2 and occludin in group F were significantly lower than those in group N (P < 0.01 or P < 0.05). The expression of APRIL, IL-17, IL-22, BAFF and sIgA on protein level were significantly down-regulated (P < 0.01 or P < 0.05), while the expression of IL-10, TGF-ß, IL-6, IL-4 were significantly up-regulated (P < 0.01) in group F. The abundances of bacteria in Firmicutes and Lactobacillus decreased significantly (P < 0.01) in group F. Our results indicated that oral administration of florfenicol might have a negative impact on functions of intestinal mucosal barrier, immune system and the intestinal microbiota.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Tianfenicol/análogos & derivados , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Firmicutes/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-10 , Jejuno/efeitos dos fármacos , Lactobacillus/efeitos dos fármacos , Masculino , Camundongos , Distribuição Aleatória , Tianfenicol/administração & dosagem , Tianfenicol/efeitos adversos , Tianfenicol/farmacologia
4.
Life Sci ; 241: 117164, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31838135

RESUMO

AIMS: This study was to assess whether andrographolide derivative (AL-1) could restore mucosal homeostasis and regulate tight junctions through MLCK-dependent pathway in DSS-induced colitis mice. MAIN METHODS: Colitis mice model was induced by daily administration of 2.5% DSS for seven days. The therapeutic effect was determined by evaluating the histopathological changes and the pro-inflammatory cytokine level. In addition, the effects of AL-1 on tight junctions were examined by immunohistochemistry and Western blot. The expressions of factors in MLCK-dependent pathway were evaluated by immunofluorescence and Western blot. KEY FINDINGS: AL-1 protected the intestinal barrier function in DSS-induced colitis mice. These protective effects were achieved by maintaining the normal mucus secretion and preserving tight junctions via suppression of the MLCK-dependent pathway. SIGNIFICANCE: AL-1 could prevent the increase in the DSS-induced intestinal permeability. These data indicated that AL-1 could be a promising agent for UC treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Permeabilidade da Membrana Celular/fisiologia , Colite/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Diterpenos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Permeabilidade da Membrana Celular/efeitos dos fármacos , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Diterpenos/química , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinase de Cadeia Leve de Miosina/metabolismo , Fosforilação , Transdução de Sinais , Junções Íntimas/metabolismo , Junções Íntimas/patologia
5.
J Agric Food Chem ; 68(1): 168-175, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31850758

RESUMO

Naringin is a polymethoxylated flavonoid commonly found in citrus species and has therapeutic potential in intestinal disorders. However, the effect and mechanism of naringin on gut-vascular barrier disruption has not yet been reported. This study aimed to investigate the distinguishing and selectively protective effects of naringin on tumor necrosis factor (TNF)-α-induced gut-vascular barrier disruption and elucidate the potential mechanism. In the present study, an in vitro gut-vascular barrier model composed of rat intestinal microvascular endothelial cells (RIMVECs) was studied. Evans blue-albumin efflux assay showed that naringin (50 µM) evidently protected the integrity of RIMVEC monolayer barriers against TNF-α-induced disruption. Naringin maintained the expression and distribution of tight junction proteins including zona occludin-1, occludin, claudin-1, and claudin-2. Additionally, naringin protected RIMVECs from TNF-α-induced apoptosis and cell migration suppression (41.1 ± 2.2 vs 51.1 ± 3.5%; 61.0 ± 5.1 vs 72.2 ± 6.2%). Our results indicate that naringin effectively ameliorates gut-vascular barrier disruption.


Assuntos
Células Endoteliais/efeitos dos fármacos , Flavanonas/farmacologia , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Apoptose/efeitos dos fármacos , Citrus/química , Claudina-1/genética , Claudina-1/metabolismo , Células Endoteliais/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Microvasos/citologia , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Ocludina/genética , Ocludina/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética
6.
Toxicol Lett ; 321: 73-82, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31862507

RESUMO

An enterogenic infection occurs when intestinal mucosal disruption is followed by the invasion of intestinal bacteria into the blood and distant organs, which can result in severe diseases or even death. Our previous study using Rhesus monkeys as an in vivo model revealed that methamphetamine (MA) induced intestinal mucosal barrier damage, which poses a high risk of enterogenic infection. However, how methamphetamine causes intestinal mucosal barrier damage remains largely unknown. In this study, we employed an in vitro model, and found that MA treatment could inhibit the expression of miR-181c, which directly targets and regulates TNF-α, and ultimately induces apoptosis and damages the intestinal barrier. Moreover, we measured TNF-α serum levels as well as the intestinal mucosal barrier damage indicators (diamine oxidase, d-lactic acid, and exotoxin) and found that their levels were significantly higher in MA-dependents than in healthy controls (P < 0.001). To the best of our knowledge, this is the first report evidencing that miR-181c is involved in MA-induced intestinal barrier injury via TNF-α regulation, which introduces novel potential therapeutic targets for MA-dependent intestinal diseases.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Estimulantes do Sistema Nervoso Central/efeitos adversos , Células Epiteliais/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Metanfetamina/efeitos adversos , MicroRNAs/metabolismo , Junções Íntimas/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/sangue , Transtornos Relacionados ao Uso de Anfetaminas/genética , Transtornos Relacionados ao Uso de Anfetaminas/patologia , Animais , Apoptose/efeitos dos fármacos , Translocação Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Estudos de Casos e Controles , Linhagem Celular , Impedância Elétrica , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Microbioma Gastrointestinal , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Permeabilidade , Ratos , Transdução de Sinais , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
7.
Gastroenterology ; 158(1): 123-136, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31470006

RESUMO

BACKGROUND & AIMS: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal-release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. METHODS: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal-release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. RESULTS: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal-release peppermint oil group had a response (46.8%, P = .170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P = .385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P = .317 and 1.6%, P = .351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P = .016), discomfort (P = .020), and IBS severity (P = .020). Adverse events, although mild, were more common in both peppermint oil groups (P < .005). CONCLUSIONS: In a randomized trial of patients with IBS, we found that neither small-intestinal-release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal-release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.


Assuntos
Dor Abdominal/tratamento farmacológico , Analgésicos/administração & dosagem , Síndrome do Intestino Irritável/tratamento farmacológico , Óleos Vegetais/administração & dosagem , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Administração Oral , Adolescente , Adulto , Idoso , Analgésicos/efeitos adversos , Cápsulas , Método Duplo-Cego , Feminino , Humanos , Mucosa Intestinal/efeitos dos fármacos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/diagnóstico , Masculino , Pessoa de Meia-Idade , Países Baixos , Medição da Dor , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
8.
J Sci Food Agric ; 100(1): 235-244, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31512251

RESUMO

BACKGROUND: This study evaluated the effects of early antibiotic exposure (EAE) on subsequent amino acid (AA) profiles and small intestinal AA transporter and receptor expression level in pigs with different dietary crude protein (CP) levels. Eighteen litters of piglets were fed creep feed diets, either with or without antibiotics while with sow on day 7. The pigs were weaned at day 23 and fed the same diets until day 42, when random pigs within each group were offered a normal- or low-CP diet, thereby creating four groups. On day 120, the pigs were euthanized, and jejunal and ileal mucosa and digesta were collected for gene-expression and AA-concentration analysis. RESULTS: With the normal-CP diet, EAE increased (P < 0.05) the concentrations of six essential amino acids (EAA) and three non-essential amino acids (NEAA) in serum, four EAAs and four NEAAs in jejunal mucosa, one EAA and two NEAAs in ileal mucosa, five EAAs and three NEAAs in jejunal digesta, and three EAAs and two NEAAs in ileal digesta. Early antibiotic exposure upregulated (P < 0.05) CAT1, ASCT2, ATB0,+ , CaSR, T1R1, and T1R3 expression in the jejunum, downregulated PepT1 expression with a normal-CP diet. It upregulated (P < 0.05) the expressions of CAT1, ATB0,+ , ATP1A1, and T1R3 in the ileum with a normal-CP diet. CONCLUSION: These results suggest that EAE has long-term effects on AA profiles, mainly in the jejunum and serum, by increasing AA transporter expression in the intestine, and that these effects may be influenced by dietary CP levels. © 2019 Society of Chemical Industry.


Assuntos
Sistemas de Transporte de Aminoácidos/genética , Aminoácidos/metabolismo , Antibacterianos/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Receptores Acoplados a Proteínas-G/genética , Suínos/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos/química , Ração Animal/análise , Animais , Antibacterianos/administração & dosagem , Proteínas na Dieta/análise , Proteínas na Dieta/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/crescimento & desenvolvimento , Mucosa Intestinal/metabolismo , Masculino , Distribuição Aleatória , Receptores Acoplados a Proteínas-G/metabolismo , Suínos/genética , Suínos/crescimento & desenvolvimento , Fatores de Tempo
9.
Arq Gastroenterol ; 56(4): 405-411, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800737

RESUMO

BACKGROUND: Serotonin (5-HT) is present in the epithelial enterochromaffin cells (EC), mast cells of the lamina propria and enteric neurons. The 5-HT is involved in regulating motility, secretion, gut sensation, immune system and inflammation. OBJECTIVE: Evaluate the effects of diabetes and quercetin supplementation on serotoninergic cells and its cell loss by apoptosis in jejunal mucosa of streptozotocin-induced diabetic rats (STZ-rats). METHODS: Twenty-four male Wistar rats were divided into four groups: normoglycemic (C), normoglycemic supplemented with 40 mg/day quercetin (Q), diabetic (D) and diabetic supplemented with 40 mg/day quercetin (DQ). After 120 days, the jejunum was collected and fixated in Zamboni's solution for 18 h. After obtaining cryosections, immunohistochemistry was performed to label 5-HT and caspase-3. Quantification of 5-HT and caspase-3 immunoreactive (IR) cells in the lamina propria, villi and crypts were performed. RESULTS: The diabetic condition displayed an increase of the number of 5-HT-IR cells in villi and crypts, while decreased number of these cells was observed in lamina propria in the jejunum of STZ-rats. In the diabetic animals, an increased density of apoptotic cells in epithelial villi and crypts of the jejunum was observed, whereas a decreased number of caspase-3-IR cells was observed in lamina propria. Possibly, quercetin supplementation slightly suppressed the apoptosis phenomena in the epithelial villi and crypts of the STZ-rats, however the opposite effect was observed on the 5-HT-IR cells of the lamina propria. Quercetin supplementation on healthy animals promoted few changes of serotoninergic function and apoptotic stimuli. CONCLUSION: These results suggest that quercetin supplementation mostly improved the serotonergic function affected by diabetes maybe due to antioxidant and anti-inflammatory properties of quercetin.


Assuntos
Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Suplementos Nutricionais , Jejuno/patologia , Quercetina/administração & dosagem , Serotonina/metabolismo , Animais , Diabetes Mellitus Experimental/patologia , Imuno-Histoquímica , Células Intersticiais de Cajal/efeitos dos fármacos , Células Intersticiais de Cajal/patologia , Mucosa Intestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
10.
Acta Cir Bras ; 34(10): e201901004, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851212

RESUMO

PURPOSE: To evaluate the effects of infliximab on the inflammation of the colonic mucosa devoid from fecal stream. METHODS: Twenty-four rats were submitted to a Hartmann's procedure. They remained for 12 weeks with the fecal derivation to development of diversion colitis on excluded colorectal stump. After this period, they were divided into 3 groups: one group received intervention with saline (2.0 mL / week), other group infliximab at doses of 5 mg/kg/week and the other 10 mg/kg/week for five consecutively weeks. Concluded the intervention period, the animals were euthanized to remove colon segments with and without fecal stream. Colitis was diagnosed by histological analysis and the degree of inflammation by validated score. The neutrophilic infiltrate was evaluated by tissue expression of myeloperoxidase identified by immunohistochemical. The tissue content of myeloperoxidase was measured by computer-assisted image analysis. RESULTS: The inflammatory score was high in colonic segments without fecal stream. The intervention with infliximab reduced the inflammatory score in excluded colonic segments. The content of myeloperoxidase was reduced in colonic segments of animals treated with infliximab mainly in high concentrations. CONCLUSION: Intervention with infliximab reduced the inflammation and the neutrophil infiltrate in colonic segments devoid of the fecal stream.


Assuntos
Colite/tratamento farmacológico , Fármacos Gastrointestinais/farmacologia , Infliximab/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Fezes , Trânsito Gastrointestinal/efeitos dos fármacos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Peroxidase/análise , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
11.
BMC Complement Altern Med ; 19(1): 337, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775739

RESUMO

BACKGROUND: Tong-Xie-Yao-Fang (TXYF) has been shown to be effective in diarrhoea-predominant irritable bowel syndrome (IBS-D) patients. However, the underlying mechanism remains to be clarified. The aim of this study was to investigate the efficacy and related mechanisms of TXYF in an IBS-D rat model. METHODS: The IBS-D rat model was established with 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. Then, IBS-D rats were divided into control, TXYF and rifaximin groups and treated intragastrically with normal saline, TXYF and rifaximin, respectively, for 14 days. The following indicators were measured before and after treatment: defecation frequency, faecal water content (FWC) and colorectal distension (CRD). Histopathological changes in the distal colon were observed after treatment. The expression of OCLN and ZO1 in the distal colon of IBS-D rats reflected the intestinal mucosal permeability, as measured by qRT-PCR, western blot, and enzyme-linked immunosorbent assays (ELISAs). The NF-κB and Notch signalling pathways and inflammation-related factors were investigated. RESULTS: After treatment with TXYF, the defecation frequency, FWC and CRD were significantly lower than those in the model group (P < 0.05). HE staining showed that colonic epithelial cells (CECs) in the IBS-D rats displayed significant oedema, impaired intestinal mucosal integrity and an increased influx of inflammatory cells. A significant reduction in granulocyte and CEC oedema was observed after the administration of TXYF and rifaximin compared to that of the model group and blank group (P < 0.05). TXYF significantly upregulated the expression of OCLN and ZO-1 and downregulated inflammation-related factors (IL-6, IL-1ß, and TNF-α and the chemokine KC) in IBS-D rats compared to those in the model group rats (P < 0.05). In terms of the NF-κB and Notch signalling pathways, the expression of NICD, p-ERK, Hes-1 and p-P65 decreased significantly in the TXYF and rifaximin groups, while the expression of ATOH1 increased significantly compared to that in the model group (P < 0.05). CONCLUSION: TXYF can effectively improve intestinal permeability and enhance intestinal mucosal barrier function, which may be related to inhibition of the inflammatory cascade and the NF-κB and Notch signalling pathways.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Absorção Intestinal/efeitos dos fármacos , Síndrome do Intestino Irritável/metabolismo , NF-kappa B/metabolismo , Receptores Notch/metabolismo , Animais , Citocinas/metabolismo , Diarreia , Modelos Animais de Doenças , Feminino , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Síndrome do Intestino Irritável/patologia , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos
12.
Environ Health Perspect ; 127(11): 117006, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31755747

RESUMO

BACKGROUND: Drinking water disinfection inadvertently leads to the formation of numerous disinfection by-products (DBPs), some of which are cytotoxic, mutagenic, genotoxic, teratogenic, and potential carcinogens both in vitro and in vivo. OBJECTIVES: We investigated alterations to global gene expression (GE) in nontransformed human small intestine epithelial cells (FHs 74 Int) after exposure to six brominated and two chlorinated DBPs: bromoacetic acid (BAA), bromoacetonitrile (BAN), 2,6-dibromo-p-benzoquinone (DBBQ), bromoacetamide (BAM), tribromoacetaldehyde (TBAL), bromate (BrO3-), trichloroacetic acid (TCAA), and trichloroacetaldehyde (TCAL). METHODS: Using whole-genome cDNA microarray technology (Illumina), we examined GE in nontransformed human cells after 4h exposure to DBPs at predetermined equipotent concentrations, identified significant changes in gene expression (p≤0.01), and investigated the relevance of these genes to specific toxicity pathways via gene and pathway enrichment analysis. RESULTS: Genes related to activation of oxidative stress-responsive pathways exhibited fewer alterations than expected based on prior work, whereas all DBPs induced notable effects on transcription of genes related to immunity and inflammation. DISCUSSION: Our results suggest that alterations to genes associated with immune and inflammatory pathways play an important role in the potential adverse health effects of exposure to DBPs. The interrelationship between these pathways and the production of reactive oxygen species (ROS) may explain the common occurrence of oxidative stress in other studies exploring DBP toxicity. Finally, transcriptional changes and shared induction of toxicity pathways observed for all DBPs caution of additive effects of mixtures and suggest further assessment of adverse health effects of mixtures is warranted. https://doi.org/10.1289/EHP4945.


Assuntos
Desinfetantes/toxicidade , Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Água Potável , Células Epiteliais/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos
13.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 800-805, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750821

RESUMO

Objective To investigate the role and mechanism of histone deacetylase 3 (HDAC3) in alcohol-induced inflammation and permeability of intestinal epithelial cells. Methods To select the proper concentration of alcohol, differentiated Caco-2 cells were treated with different concentrations (10, 25, 50, 100 and 200 mmol/L) of alcohol, and then cell viability was assayed by MTT assay; the mRNA and protein levels of HDAC3 were analyzed by real-time PCR and Western blot analysis. Differentiated Caco-2 cells were divided into three groups: control group, alcohol group (treatment with 50 mmol/L alcohol for 60 minutes), and alcohol combined with HDAC3 inhibitor group (pretreatment with 2 µmol/L RGFP966 1 hour before alcohol). ELISA was performed to detect tumor necrosis factor α (TNF-α) level in cell supernatant. Transepithelial electrical resistance (TER) was measured using a resistance meter. Western blot analysis was used to determine the protein levels relevant to tight junction (occludin and claudin-1) and NF-κB activation (IκB and phosphorylated NF-κBp65). Results Alcohol at 10, 25 and 50 mmol/L did not affect cell viability. The mRNA and protein expression levels of HDAC3 increased in a dose-dependent manner after alcohol treatment at these concentration s. Compared with the control group, TNF-α and phosphorylated NF-κBp65 levels increased, whereas TER and protein levels of occludin, claudin-1 and IκB decreased in the alcohol group. Compared with the alcohol group, TNF-α and phosphorylated NF-κBp65 levels were reduced, while TER and protein levels of occludin, claudin-1 and IκB were elevated in the alcohol combined with HDAC3 inhibitor group. Conclusion HDAC3 inhibition can attenuate alcohol-induced inflammation and permeability of intestinal epithelial cells, which may be related to the inactivation of NF-κB.


Assuntos
Etanol/efeitos adversos , Inibidores de Histona Desacetilases/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Fator de Transcrição RelA/antagonistas & inibidores , Células CACO-2 , Claudina-1/metabolismo , Histona Desacetilases , Humanos , Proteínas I-kappa B/metabolismo , Inflamação , Mucosa Intestinal/patologia , Ocludina/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa
14.
J Agric Food Chem ; 67(48): 13282-13298, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690068

RESUMO

Dietary supplementation with conjugated linoleic acid (CLA) has been reported to alleviate the effect of colitis in mice, but the mechanisms involved need further exploration. The study aimed to investigate how orally administered CLA alleviates dextran sulfate sodium (DSS)-induced colitis in mice. CLA was administered in five different doses: 40, 20, 10, 5, and 2.5 mg/day. Doses of CLA at 10 mg/day and higher alleviated colitis symptoms and reduced inflammation induced by DSS, in which 40, 20, and 10 mg/day CLA significantly increased the concentration of mucin2 and goblet cells, but neither 5 mg/day CLA nor 2.5 mg/day CLA had any effects. Meanwhile, 40 and 20 mg/day CLA treatments significantly upregulated the concentration of tight junction proteins (ZO-1, occludin, and claudin-3) and ameliorated epithelial apoptosis caused by DSS. Moreover, oxidative-stress-related enzymes (superoxide dismutase, glutathione peroxidase, and catalase) and inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-10, and IL-6] were modulated by 40 and 20 mg/day CLA. Furthermore, 40 mg/day CLA rebalanced the gut microbiota damaged by DSS, including reducing Bacteroides and increasing Bifidobacterium and Odoribacter. In conclusion, CLA supplementation alleviated DSS-induced colitis in a dose-dependent manner by modulating inflammatory cytokines and oxidation stress, maintaining the mucosal barrier, and reverting microbiota changes.


Assuntos
Colite/tratamento farmacológico , Citocinas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Ácidos Linoleicos Conjugados/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , Citocinas/genética , Sulfato de Dextrana/efeitos adversos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
Cell Physiol Biochem ; 53(5): 851-864, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31714043

RESUMO

BACKGROUND/AIMS: The growth promoting effect of lysine and betaine as well as the expression of candidate genes reflecting their efficacy, such as ghrelin, leptin, Growth Hormone Secretagogue Receptor (GHS-R), Insulin like Growth Factor (IGF- 1) and Growth Hormone Releasing Hormone (GHRH) was examined in Labeo rohita fingerlings. METHODS: One hundred eighty healthy juveniles from a homologous population were randomly distributed to 15 rectangular tanks of 150 litres capacity. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. At the end of trial, the growth parameters such as weight gain, SGR, PER were estimated from the weight of the triplicate groups. The digestive, metabolic and antioxidant enzymes were analysed using spectrophotometric methods. The intestine, brain and liver were sampled from the treatments and expression of different genes ghrelin, leptin, GHSR, IGF-1 and GHRH was also performed by realtime PCR. RESULTS: A significant (P<0.05) increase in weight gain, SGR, PER and lowest FCR was found in T4 group which was significantly (p < 0.05) different from other experimental groups. The highest mRNA expression levels of expression were found in T4 group which was similar to that of ghrelin gene mRNA of T2 group. The significantly (p<0.05) highest GHSR, GHRH and IGF-1 gene expression levels were found in T4 treatment group compared to other groups. CONCLUSION: The present study reveals that the lysine and betaine stimulate growth and expression of ghrelin GHRH, GHS-R and IGF-1 genes. The increase of IGF-I mRNA expression with lysine and betaine supplementation revealed that these compounds act as growth modulators. However, lysine was found to be a more potent modulator of growth compared to betaine.


Assuntos
Betaína/farmacologia , Cyprinidae/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Lisina/farmacologia , Ração Animal , Animais , Catalase/metabolismo , Cyprinidae/crescimento & desenvolvimento , Grelina/genética , Grelina/metabolismo , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Leptina/genética , Leptina/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Superóxido Dismutase/metabolismo
16.
Arq Bras Cir Dig ; 32(3): e1451, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31644671

RESUMO

BACKGROUND: Hypovolemic shock is a common disease in polytrauma patients and may develop ischemia in various organs, increasing morbidity and mortality. The bowel is usually most affected by this condition. AIM: To evaluate the effects of copaiba oil on the intestinal mucosa's injury of rats submitted to hypovolemic shock. METHOD: Fifteen rats were divided into three groups: sham - simulated surgery; ischemia - animals submitted to hypovolemic shock; and copaiba - animals submitted to hypovolemic shock previously treated with copaiba oil. Mean blood pressure, arterial blood gas after shock induction, degree of intestinal lesion and villus length were evaluated. RESULTS: The sham presented the lowest values of lactate and PaCO2 and the highest values of mean arterial pressure, pH and bicarbonate in relation to the other groups. The degree of mesenteric lesion was zero in the sham group; 3.00±1.00 in the ischemia group; and 3.00±0.71 in the copaiba group. The villus length was 173.60±8.42 in the sham, 142.77±8.33 in the ischemia and 143.01±9.57 in the copaiba group. There was a significant difference between the sham and the other groups (p<0.05); however, there not significant difference between groups Ischemia and copaiba. CONCLUSION: Administration of copaiba oil did not reduce the intestinal mucosa lesion of rats after hypovolemic shock.


Assuntos
Anti-Inflamatórios/farmacologia , Fabaceae/química , Mucosa Intestinal/efeitos dos fármacos , Óleos Vegetais/farmacologia , Choque , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Íleo/patologia , Mucosa Intestinal/patologia , Isquemia/tratamento farmacológico , Masculino , Óleos Vegetais/química , Óleos Vegetais/uso terapêutico , Distribuição Aleatória , Ratos Wistar , Choque/tratamento farmacológico
17.
J Dairy Sci ; 102(12): 10772-10778, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629525

RESUMO

Colostrum plays an important role in initiating the development of the intestinal barrier in newborn mammals. Given its bioactivity, there is much interest in the potential use of bovine colostrum to improve human gastrointestinal health throughout the life span. There is evidence that bovine colostrum is effective at improving small intestinal barrier integrity and some indication that it may alter colonic motility. However, for colostrum to be used as a product to improve intestinal health, it needs to be bioactive after processing. The aim of this study was to determine whether industrial processing of bovine colostrum affects its ability to improve small intestinal barrier integrity or alter distal colon motility. Three colostrum sample types were compared; raw whole colostrum powder (WCP), raw skim colostrum powder (SCP), and industrially produced colostrum milk protein concentrate (CMPC). To determine whether these colostrum powders had different effects on small intestinal barrier integrity, their effects on the transepithelial electrical resistance across an in vitro intestinal epithelial layer (Caco-2 cells) were measured, both with and without a challenge from the proinflammatory cytokine tumor necrosis factor-α. These results showed that CMPC enhanced transepithelial electrical resistance across unchallenged epithelial cell layers, whereas the raw colostrum samples, WCP and SCP, did not have an effect. The colostrum samples were also compared to determine how they affect contractility in the distal colon isolated from the rat. Skim colostrum powder was the only sample to act directly on colonic tissue to modulate motility, increasing the amplitude of contractions. The results show that bovine colostrum is able to improve small intestinal barrier integrity and alter colon motility, and they implicate different components. The barrier integrity enhancement was apparent only in the industrial CMPC, which may have been due to the increase in protein concentration or the release of small peptides as a result of processing. The ability to alter colon motility was present in SCP but absent in WCP, again implying that an increase in protein concentration is responsible for the effect. However, this effect was not apparent for the industrially processed CMPC, suggesting denaturation or degradation of the active component. The beneficial effect of colostrum on small intestinal barrier integrity was present after processing, confirming that it is feasible to industrially produce an active product for gut health.


Assuntos
Colostro , Mucosa Intestinal/efeitos dos fármacos , Proteínas do Leite/farmacologia , Animais , Células CACO-2 , Bovinos , Humanos , Proteínas do Leite/metabolismo , Ratos , Fator de Necrose Tumoral alfa/metabolismo
18.
J Anim Sci ; 97(11): 4548-4556, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31603198

RESUMO

The objectives of the current study were to explore the effects of mannan oligosaccharide (MOS) supplementation in the diets of sow and (or) their offspring on intestinal bacteria, intestinal and systemic inflammation in the piglet. A total of 60 multiparous sows (4 ± 1 parity; Landrace × Yorkshire) were fed either control diet (sCON, n = 30) or a diet containing 400 mg kg-1 MOS (sMOS, n = 30) from day 86 of gestation until weaning (day 20 of postpartum). On day 7 of age, offspring (Duroc × Landrace Yorkshire) were assigned within sow treatments and fed control diet (pCON) or diet containing 800 mg kg-1 MOS (pMOS) for 28 d (end at 35 d of age), resulting in four piglet diet groups (n = 15 litters per diet group): sCON-pCON, sCON-pMOS, sMOS-pCON, and sMOS-pMOS. Results found that piglet diet MOS increased or tend to increase Lactobacillus amount in the ileum digesta (P < 0.01) and jejunum digesta (P = 0.07), respectively; while tend to decrease Escherichia coli amount in jejunum digesta (P =0.06) and cecum digesta (P = 0.08). Both sow and piglet diets add MOS (sMOS-pMOS) increased Lactobacillus amount but decreased E. coli amount in jejunum digesta (P < 0.05) compared with the sCON-pCON diet group. In addition, sow diet MOS (rather than piglet diet MOS) increased sIgA content in piglet jejunum mucosa compared with control (P = 0.04). Sow diet MOS decreased toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), and interleukin 8 (IL-8) mRNA levels (P < 0.05) and tended to decrease nuclear factor-κB p65 (NF-κB p65) mRNA level (P = 0.07) in piglet intestinal lymphatic. The interaction effects between sow and piglet diets were found on the mRNA levels of NF- κB p65 (P = 0.03) and IL-8 (P = 0.02) in piglet jejunum. Finally, the sow diet MOS decreased proinflammatory cytokines IL-2 (P < 0.01) and IL-4 (P < 0.01) concentrations in piglet serum. Piglets diet MOS decreased the contents of IL-2 (P = 0.03), IL-4 (P = 0.01) and interferon (IFN)-γ (P < 0.01) while increased anti-inflammatory cytokine IL-10 (P < 0.01) content in serum. The interaction effects between sows and piglet diets on IL-4 (P = 0.02), IL-10 (P < 0.01), and IFN-γ (P = 0.08) were observed. In conclusion, sow and/or piglet diet MOS could improve intestinal microbiota, enhance intestinal mucosal immune competence, and suppress intestinal and systemic inflammation in the piglet.


Assuntos
Suplementos Nutricionais/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Mananas/administração & dosagem , Oligossacarídeos/administração & dosagem , Suínos/fisiologia , Ração Animal/análise , Animais , Animais Recém-Nascidos , Dieta/veterinária , Feminino , Inflamação/veterinária , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Masculino , Paridade , Gravidez , Suínos/imunologia
19.
Medicine (Baltimore) ; 98(39): e17285, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574846

RESUMO

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), among cytokines that mediate the inflammatory process, plays an important role in diseases involving the loss of intestinal barrier integrity. Several molecules with anti-TNF-alpha activity have been studied aiming to develop new therapies. The purpose of this paper is to describe the systematic review protocol of experimental studies that determine mechanisms of action of molecules with anti-TNF-alpha activity on intestinal barrier inflammation. METHODS: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P). The databases to be searched are PubMed, EMBASE, Scopus, ScienceDirect, and Web of Science. Experimental studies in rats or mice that assessed the activity of anti-TNF-alpha molecules in models of intestinal barrier inflammation will be included in the systematic review. Studies characteristics, experimental model, and main results will be described and the bias risk assessment will be performed. Two independent reviewers will perform study selection, data extraction, and methodological quality assessment. A narrative synthesis will be made for the included studies. Also, if sufficient data is available, a meta-analysis will be conducted. I statistics will be used to assess heterogeneity. RESULTS: The present protocol will assist in producing a systematic review that identifies the mechanisms underlying the reduction of TNF-alpha in intestinal barrier inflammation models. CONCLUSION: The systematic review may contribute to the theoretical basis of research on new molecules with anti-TNF-alpha potential and, consequently, in the development of new therapies employed in humans. PROSPERO REGISTRATION NUMBER: CRD42019131862.


Assuntos
Fármacos Gastrointestinais/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Animais , Humanos , Inflamação , Projetos de Pesquisa , Revisão Sistemática como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
20.
J Agric Food Chem ; 67(39): 10871-10879, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31517482

RESUMO

This study evaluated the effect of triterpenoids from edible mushroom Poria cocos on intestinal epithelium integrity and revealed the transcriptional regulatory pathways that underpin restorative mechanisms in the gut. Based on computational docking studies, transcriptional activation experiments and glucocorticoid receptor (GR) protein immunofluorescence localization assays in cultured cells, 16α-hydroxytrametenolic acid (HTA) was discovered as a novel GR agonist in this study. HTA ameliorates TNF-α-induced Caco-2 monolayer intestinal epithelial barrier damage and suppressed activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), which attenuated downstream IκB and nuclear factor kappa-B (NF-κB) phosphorylation through GR activation. Moreover, HTA prevented NF-κB translocation into the nucleus and binding to its cis-element and suppressed lipopolysaccharide-induced downstream NO production and pro-inflammatory cytokines at both protein and mRNA expression levels. In conclusion, HTA from P. cocos improves intestinal barrier function through a GR-mediated PI3K/Akt/NF-κB signaling pathway and may be potentially exploited as a supportive dietary therapeutic strategy for restoring gut health.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Glucocorticoides/metabolismo , Triterpenos/farmacologia , Wolfiporia/química , Células CACO-2 , Humanos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Mucosa Intestinal/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/genética , Fosfatidilinositol 3-Quinase/genética , Fosforilação , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/genética , Receptores de Glucocorticoides/genética , Transdução de Sinais/efeitos dos fármacos , Triterpenos/química , Verduras/química
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