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1.
Food Chem Toxicol ; 135: 110936, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31682933

RESUMO

Palygorskite (PGS) is a kind of clay minerals with the property of absorbent capacity, and ginger essential oil (GEO) is a kind of natural antibacterial substances. In the present study PGS was used as carrier of GEO, and thus, a kind of new anti-bacterial composite GEO-PGS has been obtained. Characterization, inhibitory effect of GEO-PGS on Escherichia coli (E. coli) and its function of improvement of intestinal health would be investigated. Results showed that characterization analysis of GEO-PGS (FTIR, TG-DSC, BET, Zeta potential, specific surface area, total pore volume and size, TEM observation) demonstrated combination of GEO and PGS, and GEO was absorbed on the surface of PGS, partially filled the micropores of PGS. GEO-PGS had obvious inhibitory effect on E.coli, in combination of the antibacterial activity of GEO and bacteria-absorbed capability of PGS. GEO-PGS also had ameliorating effect on enteritis and intestinal dysfunction in vivo, which might be related to the inhibition of gene expression of inflammatory cytokines (TLR2, IL-6, TNFα, and IL-8). In conclusion, the novel composite GEO-PGS has the potential usage as functional component having effect of improving intestinal health.


Assuntos
Antibacterianos/uso terapêutico , Enterite/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Gengibre/química , Compostos de Magnésio/uso terapêutico , Óleos Voláteis/uso terapêutico , Compostos de Silício/uso terapêutico , Animais , Citocinas/genética , Citocinas/metabolismo , Sinergismo Farmacológico , Enterite/microbiologia , Expressão Gênica/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Camundongos , Testes de Sensibilidade Microbiana
2.
Ecotoxicol Environ Saf ; 187: 109846, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31677563

RESUMO

At present, the public is paying more attention to the adverse effects of pesticides on human and animal health and the environment. Glyphosate is a broad-spectrum pesticide that is widely used in agricultural production. In this manuscript, the effects of diets containing glyphosate on intestinal morphology, intestinal immune factors, intestinal antioxidant capacity and the mRNA expression associated with the Nrf2 signaling pathway were investigated in weaned piglets. Twenty-eight healthy female hybrid weaned piglets (Duroc × Landrace × Yorkshire) were randomly selected with an average weight of 12.24 ±â€¯0.61 kg. Weaned piglets were randomly assigned into 4 treatment groups and fed a basal diet supplemented with 0, 10, 20, and 40 mg/kg glyphosate for a 35-day feeding trial. We found that glyphosate had no effect on intestinal morphology. In the duodenum, glyphosate increased the activities of CAT and SOD (linear, P < 0.05) and increased the levels of MDA (linear and quadratic, P < 0.05). In the duodenum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P < 0.05) and NQO1 (linear and quadratic, P < 0.05) and reduced the relative mRNA expression levels of GPx1, HO-1 and GCLM (linear and quadratic, P < 0.05). In the jejunum, glyphosate remarkably increased the relative mRNA expression levels of Nrf2 (linear and quadratic, P < 0.05) and decreased the relative mRNA expression levels of GCLM (linear and quadratic, P < 0.05). Glyphosate increased the mRNA expression levels of IL-6 in the duodenum (linear and quadratic, P < 0.05) and the mRNA expression levels of IL-6 in the jejunum (linear, P < 0.05). Glyphosate increased the mRNA expression of NF-κB in the jejunum (linear, P = 0.05). Additionally, the results demonstrated that glyphosate linearly decreased the ZO-1 mRNA expression levels in the jejunum and the mRNA expression of claudin-1 in the duodenum (P < 0.05). In the duodenum, glyphosate increased the protein expression levels of Nrf2 (linear, P = 0.025). Overall, glyphosate exposure may result in oxidative stress in the intestines of piglets, which can be alleviated by enhancing the activities of antioxidant enzymes and self-detoxification.


Assuntos
Antioxidantes/metabolismo , Exposição Dietética/efeitos adversos , Glicina/análogos & derivados , Intestino Delgado/efeitos dos fármacos , Praguicidas/toxicidade , Ração Animal , Animais , Exposição Dietética/análise , Feminino , Glicina/toxicidade , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Suínos , Desmame
3.
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
4.
Molecules ; 24(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547332

RESUMO

Some studies have demonstrated that acrylamide (AA) was correlated with oxidative stress, resulting in physical damage. The jackfruit flake was an immature pulp that contained a high level of antioxidant activity. This study aimed to assess the defensive efficacy of jackfruit flake in AA-induced oxidative stress before and after simulated gastrointestinal digestion. Our results indicate that the total polyphenol content of Jackfruit flake digest (Digestive products of jackfruit flake after gastrointestinal, JFG) was diminished; however, JFG had raised the relative antioxidant capacity compared to Jackfruit flake extract (JFE). Additionally, the results of High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) implied that a proportion of compounds were degraded/converted into other unknown and/or undetected metabolites. Further, by high content analysis (HCA) techniques, JFG markedly reduced cytotoxicity and excessive production of reactive oxygen species (ROS) in cells, thereby alleviating mitochondrial disorders. In this study, it may be converted active compounds after digestion that had preferable protective effects against AA-induced oxidative damage.


Assuntos
Antioxidantes/análise , Artocarpus/química , Estresse Oxidativo/efeitos dos fármacos , Acrilamida/toxicidade , Apoptose/efeitos dos fármacos , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Digestão , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Espectrometria de Massas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Permeabilidade , Polifenóis/análise , Espécies Reativas de Oxigênio/metabolismo , Estômago/efeitos dos fármacos
6.
Adv Exp Med Biol ; 1155: 1049-1056, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468466

RESUMO

This study investigated the effects of taurine on bowel inflammation resulting from heat stress in broilers, with the intent of providing insight into potential improvement of the condition of broilers. A total of 300 healthy 1 day AA broilers were selected, fed normally until day 7, and allocated randomly to 5 treatment groups, namely, the control group(C), the heat stress group(HS), the low Tau (LTau) group, the middle Tau (MTau) group and the high Tau (HTau) group, which represent low, medium and high concentrations of taurine respectively. In the study, various concentrations of taurine were added to the drinking water. The Heat Stress model was produced by maintaining Broilers in a room at 34 °C.Heat stress persisted for 6 h, 12 h, 7 days, and 14 days. The results showed that the expression levels of TNF-α, IFN-γ, and IL-1ß of the HTau group were significantly lower than that of the HS group at all time points examined (6 h, 12 h, 7 days, and 14 days) (P < 0.05). Compared with the HS group subjected to 6 h, 12 h and 14 days of heat stress, the MTau group exhibited significantly lower degrees of TNF-α and IL-1ß expression. Moreover, the expression of IFN-γ was higher in the HS group after 6 h, 12 h and 7 days of heat stress than that of the MTau group subjected to similar times of heat stress (P < 0.05).There were no significant difference among the groups at other periods of heat stress (P > 0.05).


Assuntos
Resposta ao Choque Térmico , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Taurina/farmacologia , Animais , Galinhas , Citocinas/metabolismo , Temperatura Alta , Distribuição Aleatória
7.
Hum Exp Toxicol ; 38(11): 1275-1282, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31378095

RESUMO

Carbon tetrachloride (CCL4) is often employed in the production of chlorofluorocarbons, petroleum refining, oil and rubber processing, and laboratory applications. Oral, subcutaneous, and inhalation exposure to CCL4 in animal studies have been shown to be capable of leading to various types of cancer (benign and malignant, liver, breast, and adrenal gland tumors). The present study also evaluated the protective role of infliximab (INF) against the deleterious effects of CCL4 on the intestinal system. Twenty-four male Sprague-Dawley rats were randomly assigned into three groups, control (n = 8), CCL4 (n = 8), and CCL4 + INF (n = 8). The control group received 1 mL isotonic saline solution only via intraperitoneal (i.p.) injection. The CCL4 group received a single i.p. dose of 2 mL/kg CCL4. The CCL4 + INF group received a single i.p. dose of 7 mg/kg INF followed 24 h later by a single dose of 2 mL/kg CCL4. All rats were euthanized 2 days following drug administration. CCL4 group samples also exhibited diffuse loss of enterocytes, vascular congestion, neutrophil infiltration, an extension of the subepithelial space and significant epithelial lifting along the length of the villi with a few denuded villous tips. In addition, CCL4 treatment increased intestinal malondialdehyde (MDA) level and caspase-3 positivity. On the other hand, INF decreased MDA levels, caspase-3 positivity, and loss of villous. Our findings suggest that CCL4 appears to exert a highly deleterious effect on the intestinal mucosa. On the other hand, INF is effective in preventing this CCL4-induced intestinal injury by reducing oxidative stress and apoptosis.


Assuntos
Infliximab/uso terapêutico , Enteropatias/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Tetracloreto de Carbono , Infliximab/farmacologia , Enteropatias/induzido quimicamente , Enteropatias/metabolismo , Enteropatias/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
8.
Nutrients ; 11(7)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336561

RESUMO

Linseed is a dietary source of plant-based ω-3 fatty acids along with fiber as well as lignans including secoisolariciresinol diglucoside (SDG). We investigated the reversal of signs of metabolic syndrome following addition of whole linseed (5%), defatted linseed (3%), or SDG (0.03%) to either a high-carbohydrate, high-fat or corn starch diet for rats for the final eight weeks of a 16-week protocol. All interventions reduced plasma insulin, systolic blood pressure, inflammatory cell infiltration in heart, ventricular collagen deposition, and diastolic stiffness but had no effect on plasma total cholesterol, nonesterified fatty acids, or triglycerides. Whole linseed did not change the body weight or abdominal fat in obese rats while SDG and defatted linseed decreased abdominal fat and defatted linseed increased lean mass. Defatted linseed and SDG, but not whole linseed, improved heart and liver structure, decreased fat vacuoles in liver, and decreased plasma leptin concentrations. These results show that the individual components of linseed produce greater potential therapeutic responses in rats with metabolic syndrome than whole linseed. We suggest that the reduced responses indicate reduced oral bioavailability of the whole seeds compared to the components.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Linho/química , Síndrome Metabólica/induzido quimicamente , Animais , Humanos , Intestino Delgado/efeitos dos fármacos , Masculino , Síndrome Metabólica/dietoterapia , Distribuição Aleatória , Ratos , Ratos Wistar
9.
Nutrients ; 11(7)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252646

RESUMO

Citrus flavanones, with hesperidin and naringin as the most abundant representatives, have various beneficial effects, including anti-oxidative and anti-inflammatory activities. Evidence also indicates that they may impact the intestinal microbiome and are metabolized by the microbiota as well, thereby affecting their bioavailability. In this review, we provide an overview on the current evidence on the intestinal fate of hesperidin and naringin, their interaction with the gut microbiota, and their effects on intestinal barrier function and intestinal inflammation. These topics will be discussed as they may contribute to gastrointestinal health in various diseases. Evidence shows that hesperidin and naringin are metabolized by intestinal bacteria, mainly in the (proximal) colon, resulting in the formation of their aglycones hesperetin and naringenin and various smaller phenolics. Studies have also shown that citrus flavanones and their metabolites are able to influence the microbiota composition and activity and exert beneficial effects on intestinal barrier function and gastrointestinal inflammation. Although the exact underlying mechanisms of action are not completely clear and more research in human subjects is needed, evidence so far suggests that citrus flavanones as well as their metabolites have the potential to contribute to improved gastrointestinal function and health.


Assuntos
Bactérias/metabolismo , Citrus/metabolismo , Colo/metabolismo , Flavanonas/metabolismo , Frutas/metabolismo , Gastroenterite/prevenção & controle , Microbioma Gastrointestinal , Hesperidina/metabolismo , Absorção Intestinal , Intestino Delgado/metabolismo , Animais , Bactérias/efeitos dos fármacos , Disponibilidade Biológica , Colo/efeitos dos fármacos , Colo/microbiologia , Flavanonas/administração & dosagem , Gastroenterite/metabolismo , Gastroenterite/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hesperidina/administração & dosagem , Humanos , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/microbiologia
10.
Clinics (Sao Paulo) ; 74: e787, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31188910

RESUMO

OBJECTIVES: Intestinal obstruction has a high mortality rate when therapeutic treatment is delayed. Resuscitation in intestinal obstruction requires a large volume of fluid, and fluid combinations have been studied. Therefore, we evaluated the effects of hypertonic saline solution (HS) with pentoxifylline (PTX) on apoptosis, oxidative stress and survival rate. METHODS: Wistar rats were subjected to intestinal obstruction and ischemia through a closed loop ligation of the terminal ileum and its vessels. After 24 hours, the necrotic bowel segment was resected, and the animals were randomized into four groups according to the following resuscitation strategies: Ringer's lactate solution (RL) (RL-32 ml/kg); RL+PTX (25 mg/kg); HS+PTX (HS, 7.5%, 4 ml/kg), and no resuscitation (IO-intestinal obstruction and ischemia). Euthanasia was performed 3 hours after resuscitation to obtain kidney and intestine samples. A malondialdehyde (MDA) assay was performed to evaluate oxidative stress, and histochemical analyses (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling [TUNEL], Bcl-2 and Bax) were conducted to evaluate kidney apoptosis. Survival was analyzed with another series of animals that were observed for 15 days. RESULTS: PTX in combination with RL or HS reduced the MDA levels (nmol/mg of protein), as follows: kidney IO=0.42; RL=0.49; RL+PTX=0.31; HS+PTX=0.34 (p<0.05); intestine: IO=0.42; RL=0.48; RL+PTX=0.29; HS+PTX=0.26 (p<0.05). The number of labeled cells for TUNEL and Bax was lower in the HS+PTX group than in the other groups (p<0.05). The Bax/Bcl-2 ratio was lower in the HS+PTX group than in the other groups (p<0.05). The survival rate on the 15th day was higher in the HS+PTX group (77%) than in the RL+PTX group (11%). CONCLUSION: PTX in combination with HS enhanced survival and attenuated oxidative stress and apoptosis. However, when combined with RL, PTX did not reduce apoptosis or mortality.


Assuntos
Apoptose/efeitos dos fármacos , Obstrução Intestinal/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pentoxifilina/farmacologia , Ressuscitação/métodos , Solução Salina Hipertônica/farmacologia , Animais , Modelos Animais de Doenças , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Obstrução Intestinal/mortalidade , Obstrução Intestinal/prevenção & controle , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Estimativa de Kaplan-Meier , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes
11.
Environ Sci Pollut Res Int ; 26(24): 24672-24682, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240658

RESUMO

Intestinal mucositis is a common side effect during radiotherapy that could be largely prevented by compounds possessing anti-inflammatory or anti-oxidant properties, including extracts of propolis containing a high proportion of flavonoids. A specially formulated aqueous extract of propolis (PWE) has been prepared in such a way to preclude the inclusion of flavonoids but contain mostly organic aromatic acids to study whether it would still protect against radiation-induced intestinal mucositis and to study the possible involvement of apoptotic pathways. Rats were exposed to a gamma radiation dose of 8 Gy from a Cesium-137 source in order to inflict intestinal mucositis. Three days before exposure, rats were given PWE orally and treatment continued for 2 more days. Twenty-four hours later, rats were sacrificed, the small intestine was excised, and sections were examined histologically. Different parameters for apoptosis, inflammation, and oxidative stress were determined in the serum and in intestinal homogenates. Radiation exposure led to histological and biochemical signs of intestinal damage. This was associated with an increase in apoptotic indicators and derangement in oxidative stress parameters. All deranged parameters were largely prevented by PWE. The findings provide evidence that the protective effect of PWE against intestinal radiation damage involves not only its anti-inflammatory and anti-oxidant effects but also its anti-apoptotic properties as well.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Raios gama/efeitos adversos , Intestino Delgado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Própole/administração & dosagem , Animais , Inflamação , Mucosite , Ratos
12.
Environ Toxicol Pharmacol ; 71: 103214, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31252312

RESUMO

Lipololysaccharides (LPS) can disrupt the gut barrier. How dose LPS affects the immune performance of mesenteric lymph nodes? The results showed the hematological parameters significantly changed after LPS treatment. The length of intestinal villus was shortened and the depth of crypts was deepened, especially on the ileum. After LPS treatment 6 h, 12 h, the number of CD3+ T cells and CD4/CD8 in the mesenteric lymph nodes of ileum were reduced significantly; the levels of IFN-γ, TNF-ɑ and IL-2 were significantly decreased, and the levels of IL-6 and IL-10 were significantly increased in the ileum. The content of sIgA in the ileum was significantly decreased after LPS treatment 3 h, 6 h and was increased after LPS treatment 12 h. LPS through mesenteric lymph nodes, which induces the immune function reduced and the ileum injured obviously after treatment 6 h. Furthermore, the performance of intestinal immune performance was the lowest after LPS treatment 6 h.


Assuntos
Citocinas/metabolismo , Endotoxinas/toxicidade , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , Animais , Citocinas/sangue , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/imunologia , Intestino Delgado/patologia , Linfonodos/imunologia , Linfonodos/patologia , Camundongos Endogâmicos , Subpopulações de Linfócitos T/imunologia
13.
PLoS Comput Biol ; 15(6): e1007100, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31242176

RESUMO

Gastrointestinal side effects are among the most common classes of adverse reactions associated with orally absorbed drugs. These effects decrease patient compliance with the treatment and induce undesirable physiological effects. The prediction of drug action on the gut wall based on in vitro data solely can improve the safety of marketed drugs and first-in-human trials of new chemical entities. We used publicly available data of drug-induced gene expression changes to build drug-specific small intestine epithelial cell metabolic models. The combination of measured in vitro gene expression and in silico predicted metabolic rates in the gut wall was used as features for a multilabel support vector machine to predict the occurrence of side effects. We showed that combining local gut wall-specific metabolism with gene expression performs better than gene expression alone, which indicates the role of small intestine metabolism in the development of adverse reactions. Furthermore, we reclassified FDA-labeled drugs with respect to their genetic and metabolic profiles to show hidden similarities between seemingly different drugs. The linkage of xenobiotics to their transcriptomic and metabolic profiles could take pharmacology far beyond the usual indication-based classifications.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Intestino Delgado , Modelos Biológicos , Administração Oral , Biologia Computacional , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Metaboloma/efeitos dos fármacos , Máquina de Vetores de Suporte , Xenobióticos/efeitos adversos , Xenobióticos/metabolismo
14.
PLoS Genet ; 15(5): e1007687, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31059499

RESUMO

The transcription factor Oct1/Pou2f1 promotes poised gene expression states, mitotic stability, glycolytic metabolism and other characteristics of stem cell potency. To determine the effect of Oct1 loss on stem cell maintenance and malignancy, we deleted Oct1 in two different mouse gut stem cell compartments. Oct1 deletion preserved homeostasis in vivo and the ability to establish organoids in vitro, but blocked the ability to recover from treatment with dextran sodium sulfate, and the ability to maintain organoids after passage. In a chemical model of colon cancer, loss of Oct1 in the colon severely restricted tumorigenicity. In contrast, loss of one or both Oct1 alleles progressively increased tumor burden in a colon cancer model driven by loss-of-heterozygosity of the tumor suppressor gene Apc. The different outcomes are consistent with prior findings that Oct1 promotes mitotic stability, and consistent with differentially expressed genes between the two models. Oct1 ChIPseq using HCT116 colon carcinoma cells identifies target genes associated with mitotic stability, metabolism, stress response and malignancy. This set of gene targets overlaps significantly with genes differentially expressed in the two tumor models. These results reveal that Oct1 is selectively required for recovery after colon damage, and that Oct1 has potent effects in colon malignancy, with outcome (pro-oncogenic or tumor suppressive) dictated by tumor etiology.


Assuntos
Carcinogênese/genética , Colo/metabolismo , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Fator 1 de Transcrição de Octâmero/genética , Animais , Azoximetano/administração & dosagem , Carcinogênese/metabolismo , Carcinogênese/patologia , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Sulfato de Dextrana/administração & dosagem , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Células HCT116 , Humanos , Integrases/genética , Integrases/metabolismo , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Camundongos , Camundongos Knockout , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator 1 de Transcrição de Octâmero/deficiência , Organoides/efeitos dos fármacos , Organoides/metabolismo , Organoides/patologia , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Regeneração , Transdução de Sinais , Análise de Sobrevida , Tamoxifeno/administração & dosagem
15.
J Ethnopharmacol ; 240: 111953, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31082513

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, there is no specific effective western medicine for functional dyspepsia (FD), especially in children. Clinically, child compound Endothelium corneum (CCEC) has shown to be effective for the therapy of FD, however, the underlying mechanism has not been elucidated yet. MATERIALS AND METHODS: FD was induced in rats by irregular diet plus dilute hydrochloric acid feeding. Gastric emptying and small intestinal transit were examined by intragastric gavage with Evans blue. Histopathology was assessed by H&E staining. Gastrointestinal hormones and brain gut peptides were measured by ELISA assay. mRNA expression level was quantified by real-time PCR. Protein expression level was detected by western blotting assay. Gut microbiota was analyzed by 16S rRNA miseq sequencing. RESULTS: CCEC significantly enhanced gastric emptying and small intestinal transit of FD rats, and prominently suppressed gastrointestinal microinflammation. At phylum level, CCEC prevented the decrease of Firmicutes and the increase of Bacteroidetes in gut of FD rats. In stomach of FD rats, MTL, CCK and VIP levels were significantly increased, which could be repressed by CCEC; however, the decreased GAS level could not be elevated by CCEC. In small intestine of FD rats, MTL and GAS levels were decreased, while VIP content was increased. These alterations could be effectively reversed by CCEC. NPY levels in serum, small intestine and hypothalamus of FD rats were significantly decreased, which could be rescued by CCEC. Moreover, the over-activated POMC/Stat3/Akt pathway in hypothalamus of FD rats could be suppressed by CCEC. CONCLUSION: CCEC enhanced gastrointestinal motility probably through rebalancing the homeostasis of brain-gut-microbiota axis in FD rats. The novel findings may provide insightful theoretical basis for its clinical employment.


Assuntos
Dispepsia/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Animais , Ciclo-Oxigenase 2/genética , Dispepsia/metabolismo , Dispepsia/microbiologia , Dispepsia/fisiopatologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Homeostase/efeitos dos fármacos , Hipotálamo/microbiologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Masculino , Medicina Tradicional Chinesa , Óxido Nítrico Sintase Tipo II/genética , Peroxidase/metabolismo , RNA Ribossômico 16S , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/fisiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Biomed Pharmacother ; 115: 108813, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054505

RESUMO

Our objective was to investigate whether a thermostable protein fraction (TPF) obtained from the larvae of Musca domestica, which contains cecropin family AMPs, is effective in treating senna leaf (Folium Sennae)-induced diarrhea in mice and its possible underlying mechanism. We did the experiments both in vitro and in vivo. Firstly, lipopolysaccharide (LPS) was used to induce inflammation in RAW 264.7 macrophages. The expression level of nitric oxide (NO) and tumor necrosis factor (TNF)-α was assessed using kits and immunofluorescence assay. A mice model of total diarrhea was established using a decoction of Folium Sennae. Levels of interleukin (IL)-6 and IL-1ß in mice serum and of TNF-α in the supernatant of jejunal tissue homogenate were measured using commercially available ELISA kits. Hematoxylin-eosin staining was employed to evaluate pathological lesions, and immunohistochemistry was used for determining IL-1ß, IL-6, and TNF-α expression levels. Results display that TPF markedly inhibited NO and TNF-α production in LPS-stimulated RAW 264.7 macrophages in vitro. Moreover, TPF significantly lowered the diarrhea index (DI) in diarrheic mice; when TPF was administered at a high dose (120 mg/kg) to mice, in comparison with mice in the model group, DI was markedly reduced. TPF could also decrease the expression levels of some pro-inflammatory factors, high dose TPF treated mice were with the reduction of (202.29 ± 18.58) pg/ml (tumor necrosis factor alpha, TNF-α), (53.69 ± 7.83) pg/ml (interleukin (IL)-1ß, IL-1ß), (48.44 ± 3.77) pg/ml (IL-6I, L-6) to the model separately. In comparison with berberine hydrochloride, which was used as the positive control in this study, TPF could confer better intestinal protection. To conclude, our results demonstrate that TPF has potent anti-inflammatory activities in vitro and antidiarrheal effects on mice with Folium Sennae-induced diarrhea.


Assuntos
Antidiarreicos/farmacologia , Diarreia/induzido quimicamente , Moscas Domésticas/química , Proteínas de Insetos/farmacologia , Animais , Antidiarreicos/química , Diarreia/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Temperatura Alta , Proteínas de Insetos/química , Intestino Delgado/efeitos dos fármacos , Larva/química , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico/metabolismo , Estabilidade Proteica , Células RAW 264.7 , Fator de Necrose Tumoral alfa/antagonistas & inibidores
17.
Dig Dis Sci ; 64(7): 1748-1758, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31076989

RESUMO

For decades, the pathogenesis of a variety of human diseases has been attributed to increased intestinal paracellular permeability even though scientific evidence supporting this hypothesis has been tenuous. Nevertheless, during the past decade, there have been a growing number of publications focused on human genetics, the gut microbiome, and proteomics, suggesting that loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately causing chronic inflammation, including autoimmunity, in genetically predisposed individuals. The gut mucosa works as a semipermeable barrier in that it permits nutrient absorption and also regulates immune surveillance while retaining potentially harmful microbes and environmental antigens within the intestinal lumen. Celiac disease (CD), a systemic, immune-mediated disorder triggered by gluten in genetically susceptible individuals, is associated with altered gut permeability. Pre-clinical and clinical studies have shown that gliadin, a prolamine component of gluten that is implicated in CD pathogenesis, is capable to disassembling intercellular junctional proteins by upregulating the zonulin pathway, which can be inhibited by the zonulin antagonist larazotide acetate. In this review, we will focus on CD as a paradigm of chronic inflammatory diseases in order to outline the contribution of gut paracellular permeability toward disease pathogenesis; moreover, we will summarize current evidence derived from available clinical trials of larazotide acetate in CD.


Assuntos
Doença Celíaca/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Glutens/imunologia , Junções Intercelulares/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Oligopeptídeos/uso terapêutico , Animais , Doença Celíaca/imunologia , Doença Celíaca/metabolismo , Toxina da Cólera/antagonistas & inibidores , Toxina da Cólera/metabolismo , Humanos , Junções Intercelulares/imunologia , Junções Intercelulares/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Oligopeptídeos/efeitos adversos , Permeabilidade
18.
Cell Mol Neurobiol ; 39(6): 883-898, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31140018

RESUMO

Increasing evidences have shown that resveratrol could protect the brain from ischemic injury; the mechanisms underlying its neuroprotective effects are multifactorial and not fully understood. It remains unclear whether resveratrol could exert neuroprotection through modulating gut-brain axis, which plays important roles in stroke pathology. In this study, C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion for 3 days. Resveratrol, when applied immediately after MCAO onset for 3 days, promoted Th1/Th2 balance towards Th2 polarization and skewed Treg/Th17 balance towards Treg in the small intestinal lamina propria (SI-LP), and decreased small intestinal pro-inflammatory cytokines expression through modulating intestinal flora at 3 days post-ischemia (dpi). Resveratrol attenuated cerebral ischemia-induced increase in the epithelial and vascular permeability of small intestine as evidenced by reduced evans blue extravasasion and decreased protein leakage by feces/plasma albumin ratio at 3 dpi. The blood levels of pro-inflammatory cytokines at 3 dpi were also attenuated by resveratrol due to inhibiting intestinal pro-inflammatory immunity and decreasing epithelial and vascular permeability. Resveratrol robustly protected against post-stroke inflammation-induced blood-brain barrier disruption not only in the cortex but also in the striatum at 3 dpi. Furthermore, resveratrol mediated smaller cerebral infarcts and less neurological deficits via decreasing the levels of pro-inflammatory cytokines in the peri-infarct area at 3 dpi. Our results for the first time demonstrated that resveratrol may inhibit systemic post-stroke inflammation and neuroinflammation via modulating intestinal flora-mediated Th17/Tregs and Th1/Th2 polarity shift in SI-LP, which may be one of the mechanisms underlying the neuroprotective effects of resveratrol.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/patologia , Trato Gastrointestinal/patologia , Neuroproteção , Traumatismo por Reperfusão/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/imunologia , Isquemia Encefálica/fisiopatologia , Permeabilidade Capilar/efeitos dos fármacos , Citocinas/sangue , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Inflamação/imunologia , Inflamação/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Neuroproteção/efeitos dos fármacos , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/fisiopatologia , Resveratrol/farmacologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia
19.
Gastroenterology ; 157(3): 637-646.e4, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31095949

RESUMO

BACKGROUND & AIMS: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. METHODS: We performed a single-site, double-blind, parallel-group, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (≥5 × 1010 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. RESULTS: Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P = .0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P = .0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. CONCLUSIONS: In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Bifidobacterium breve/crescimento & desenvolvimento , Microbioma Gastrointestinal , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/microbiologia , Probióticos/administração & dosagem , Úlcera/prevenção & controle , Adolescente , Adulto , Endoscopia por Cápsula , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Intestino Delgado/patologia , Irlanda , Masculino , Probióticos/efeitos adversos , Fatores de Tempo , Úlcera/induzido quimicamente , Úlcera/microbiologia , Úlcera/patologia , Adulto Jovem
20.
Pak J Pharm Sci ; 32(2 (Supplementary)): 751-757, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103967

RESUMO

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75µg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.


Assuntos
Acetaminofen/farmacocinética , Microbioma Gastrointestinal/fisiologia , Acetaminofen/administração & dosagem , Acetaminofen/análise , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Microbioma Gastrointestinal/efeitos dos fármacos , Absorção Intestinal , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Masculino , Ratos
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