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‣ Effects of short chain fatty acids on effector mechanisms of neutrophils

VINOLO, Marco A. R.; HATANAKA, Elaine; LAMBERTUCCI, Rafael H.; NEWSHOLME, Philip; Curi, Rui
Fonte: JOHN WILEY & SONS LTD Publicador: JOHN WILEY & SONS LTD
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
129.57609%
Short chain fatty acids (SCFAs) are metabolic by products of anerobic bacteria fermentation. These fatty acids, despite being an important fuel for colonocytes, are also modulators of leukocyte function. The aim of this study was to evaluate the effects of SCFAs (acetate, propionate, and butyrate) on function of neutrophils, and the possible mechanisms involved. Neutrophils obtained from rats by intraperitoneal lavage 4 h after injection of oyster glycogen solution (1%) were treated with non toxic concentrations of the fatty acids. After that, the following measurements were performed: phagocytosis and destruction of Candida albicans, production of ROS (O(2)(center dot-), H(2)O(2), and HOCl) and degranulation. Gene expression (p47(phox) and p22(phox)) and protein phosphorylation (p47(phox)) were analyzed by real time reverse transcriptase chain reaction (RT-PCR) and Western blotting, respectively. Butyrate inhibited phagocytosis and killing of C. albicans. This SCFA also had an inhibitory effect on production of O(2)(center dot-), H(2)O(2), and HOCI by neutrophils stimulated with PMA or fMLP. This effect of butyrate was not caused by modulation of expression of NADPH oxidase subunits (p47(phox) and p22(phox)) but it was in part due to reduced levels of p47(phox) phosphorylation and an increase in the concentration of cyclic AMP. Acetate increased the production of O(2)(center dot-) and H(2)O(2)...

‣ Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils

VINOLO, Marco A. R.; RODRIGUES, Hosana G.; HATANAKA, Elaine; SATO, Fabio T.; SAMPAIO, Sandra C.; CURI, Rui
Fonte: ELSEVIER SCIENCE INC Publicador: ELSEVIER SCIENCE INC
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
129.34087%
Short chain fatty acids (SCFAs) are fermentation products of anaerobic bacteria. More than just being an important energy source for intestinal epithelial cells, these compounds are modulators of leukocyte function and potential targets for the development of new drugs. The aim of this study was to evaluate the effects of SCFAs (acetate, propionate and butyrate) on production of nitric oxide (NO) and proinflammatory cytokines [tumor necrosis factor alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant-2 (CINC-2 alpha beta)] by rat neutrophils. The involvement of nuclear factor kappa B (NF-kappa B) and histone deacetylase (HDAC) was examined. The effect of butyrate was also investigated in vivo after oral administration of tributyrin (a pro-drug of butyrate). Propionate and butyrate diminished TNF-alpha, CINC-2 alpha beta and NO production by LPS-stimulated neutrophils. We also observed that these fatty acids inhibit HDAC activity and NF-kappa B activation, which might be involved in the attenuation of the LPS response. Products of cyclooxygenase and 5-lipoxygenase are not involved in the effects of SCFAs as indicated by the results obtained with the inhibitors of these enzymes. The recruitment of neutrophils to the peritonium after intraperitoneal administration of a glycogen solution (1%) and the ex vivo production of cytokines and NO by neutrophils were attenuated in rats that previously received tributyrin. These results argue that this triglyceride may be effective in the treatment of inflammatory conditions. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.; FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); CAPES Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

‣ Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites

VINOLO, Marco A. R.; RODRIGUES, Hosana G.; HATANAKA, Elaine; HEBEDA, Cristina B.; FARSKY, Sandra H. P.; Curi, Rui
Fonte: PORTLAND PRESS LTD Publicador: PORTLAND PRESS LTD
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
119.46061%
SCFAs (short-chain fatty acids) are produced by anaerobic bacterial fermentation. Increased concentrations of these fatty acids are observed in inflammatory conditions, such as periodontal disease, and at sites of anaerobic infection. In the present study, the effect of the SCFAs acetate, propionate and butyrate on neutrophil chemotaxis and migration was investigated. Experiments were carried out in rats and in vitro. The following parameters were measured: rolling, adherence, expression of adhesion molecules in neutrophils (L-selectin and beta 2 integrin), transmigration, air pouch influx of neutrophils and production of cytokines [CINC-2 alpha beta (cytokine-induced neutrophil chemoattractant-2 alpha beta), IL-1 beta (interleukin-1 beta), MIP-1 alpha (macrophage inflammatory protein-1 alpha) and TNF-alpha (tumour necrosis factor-alpha)]. SCFAs induced in vivo neutrophil migration and increased the release of CINC-2 alpha beta into the air pouch. These fatty acids increased the number of rolling and adhered cells as evaluated by intravital microscopy. SCFA treatment increased L-selectin expression on the neutrophil surface and L-selectin mRNA levels, but had no effect on the expression of beta 2 integrin. Propionate and butyrate also increased in vitro transmigration of neutrophils. These results indicate that SCFAs produced by anaerobic bacteria raise neutrophil migration through increased L-selectin expression on neutrophils and CINC-2 alpha beta release.; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2004/12137-1]; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2006/00372-1]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)[23038.039417/2008-4]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)[471574/2007-4]; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

‣ Ácidos graxos de cadeia curta, produtos do metabolismo da microbiota intestinal, protegem da lesão renal aguda.; Short chain fatty acid, a metabolism product from gut microbiota, protect from acute kidney injury.

Oliveira, Vinicius de Andrade
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 05/12/2014 Português
Relevância na Pesquisa
108.77879%
Os ácidos graxos de cadeia curta (AGCC) são produzidos pela microbiota intestinal e possuem papéis anti-inflamatórios e ação inibitória sobre histona deacetilases. A lesão renal aguda (LRA) é caracterizada por uma inflamação renal que influencia a função do rim. Este projeto avaliou se o tratamento com os AGCC impactaria nos desfechos inflamatórios da LRA em camundongos. Foi observado que o tratamento com AGCC, protege da LRA. Esta melhora foi associada a uma menor inflamação e menor taxa de apoptose. Além disso, o tratamento com acetato diminuiu a atividade de histona deacetilase. Administrando bactérias produtoras de acetato, também foi possível observar uma proteção da LRA, junto de uma menor inflamação sistêmica. Esta proteção do AGCC na LRA foi também observada em modelo de LRA secundária à sepse In vitro, o tratamento com AGCC modularam tanto células imunes como células renais sob estímulos inflamatórios e de hipóxia. AGCC modulam processos inflamatórios no rim via ações epigenéticas ou não, podendo ser uma promissora ferramenta na proteção da LRA.; Short-Chain Fatty Acids (SCFA) are produced by the intestinal microbiota and have anti-inflammatory and histone deacetylases inhibitors properties. Acute kidney injury (AKI) is characterized by renal inflammation that may impair kidney function. This project evaluated whether treatment with SCFA inflammatory impacts the outcomes of AKI in mice. It was observed that treatment with SCFA protected the AKI. This improvement was associated with less inflammation and lower apoptosis rate. In addition...

‣ Enhanced mucosal re-epithelialization induced by short chain fatty acids in experimental colitis

Aguilar-Nascimento,J.E.; França-da-Silva,L.R.; de-Oliveira,A.F.; Gomes-da-Silva,M.H.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/1999 Português
Relevância na Pesquisa
129.16411%
The short chain fatty acids (SCFA) are the best nutrients for the colonocytes. Glucose is poorly used as a fuel but may be transformed into SCFA by colonic bacteria. The aim of this study was to investigate the effect of SCFA or glucose on experimental colitis. Colitis was induced in 30 Wistar rats by colonic instillation of 4% acetic acid. Five days later they were randomized to receive twice a day colonic lavage containing saline (controls, N = 10), 10% hypertonic glucose (N = 10) or SCFA (N = 10) until day 8 when they were killed. At autopsy, the colon was removed and weighed and the mucosa was evaluated macro- and microscopically and stripped out for DNA assay. Data are reported as mean ± SD or median [range] as appropriate. All animals lost weight but there was no difference between groups. Colon weight was significantly lower in the SCFA group (3.8 ± 0.5 g) than in the control (5.3 ± 2.1 g) and glucose (5.2 ± 1.3 g) groups (P<0.05). Macroscopically, the severity of inflammation was less in SCFA (grade 2 [1-5]) than in control (grade 9 [4-10]) and glucose-treated (grade 9 [2-10]) animals (P<0.01). Microscopically, ulceration of the mucosa was more severe in the glucose and control groups than in the SCFA group. The DNA content of the mucosa of SCFA-treated animals (8.2 [5.0-20.2] mg/g of tissue) was higher than in glucose-treated (5.1 [4.2-8.5] mg/g of tissue; P<0.01) and control (6.2 [4.5-8.9] mg/g of tissue; P<0.05) animals. We conclude that SCFA may enhance mucosal re-epithelialization in experimental colitis...

‣ Intraluminal injection of short chain fatty acids diminishes intestinal mucosa injury in experimental ischemia-reperfusion

Aguilar-Nascimento,José Eduardo de; Salomão,Alberto Bicudo; Nochi Jr.,Rubens Jardim; Nascimento,Mariana; Neves,José de Souza
Fonte: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia Publicador: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2006 Português
Relevância na Pesquisa
129.16411%
PURPOSE: Investigated the effect of intraluminal short-chain fatty acids (SCFA) on the intestinal mucosa in the presence of ischemia-reperfusion injury (IRI). METHODS: Six blind sacs of the small bowel (3at the jejunum and 3 at the ileum) were created in ten Wistar rats. The lateral sacs of both bowel regions were subjected to IRI (15/15 minutes) while the medial sacs were let free to receive blood supply. In the lateral sacs, it was injected either a solution containing SCFA (butyrate, propionate and acetate) or pure saline at the bowel lumen. No fluid was injected in the medial sacs. RESULTS: Both at the jejunum and at the ileum the score of the mucosal injury was higher in saline than in control sacs. SCFA treated sacs showed lesser score at the ileum (p=0.03) but were not significantly different at the jejunum (p=0.83) when compared with saline sacs. It was found a significant greater number of neutrophils (p < 0.01) in the sacs treated with saline than in the other two sacs in both regions. CONCLUSION: SCFA protect the distal small bowel mucosa and diminishes infiltration of neutrophils to the gut lamina propria in IRI.

‣ Glutamine alone or combined with short-chain fatty acids fails to enhance gut adaptation after massive enterectomy in rats

Neves,José de Souza; Aguilar-Nascimento,José Eduardo de; Gomes-da-Silva,Maria Helena Gaiva; Cavalcanti,Rosecélia Nunes; Bicudo,Alberto Salomão; Nascimento,Mariana; Nochi Jr.,Rubens Jardim
Fonte: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia Publicador: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2006 Português
Relevância na Pesquisa
109.34087%
PURPOSE: To investigate the effect of oral glutamine alone or combined with short chain fatty acids (SCFA) in the intestinal adaptation of rats submitted to an massive enterectomy. METHODS: After receiving 70% small bowel resection, 30 Wistar rats were randomized to received either standard rat chow (control group, n=10) or the same diet supplemented with 3,05% of glutamine alone (glutamine group, n=10) or combined with a solution containing SCFA (glutamine+SCFA group, n=10). Animals were killed on the 14th postoperative day. Mucosal weight, crypt depth, villus height, wall width, and the mucosal content of DNA, were assessed in basal conditions (resected gut specimen) and compared to the small bowel specimen collected on the postoperative day 14, at both jejunum and ileum sites. RESULTS: All groups presented similar pattern in weight evolution. In all groups, both the morphological findings and the DNA content were significantly higher at the end of the experiment than in basal conditions, at both the jejunum and ileum. Except for the jejunum wall width that was higher in control group (808±95 µ) than in the other two groups (glutamine = 649±88 µ and glutamine+SCFA = 656±92; p<0.01), there was no difference among them in all variables at both intestinal sites after 14 days. CONCLUSION: All groups presented adaptation of the intestinal mucosa in the remnant gut. Glutamine combined or not with short chain fatty acids fails to influence the adaptive response of the small bowel.

‣ Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

Oliveira,Ariano Jose Freitas de; Pinto Júnior,Francisco Edilson Leite; Formiga,Maria Célia Carvalho; Melo,Syomara Pereira da Costa; Brandao-Neto,Jose; Ramos,Ana Maria de Oliveira
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2010 Português
Relevância na Pesquisa
119.76304%
OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy.

‣ Role of Endogenous Growth Regulators in Seed Dormancy of Avena fatua: I. Short Chain Fatty Acids

Metzger, James D.; Sebesta, Deborah K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1982 Português
Relevância na Pesquisa
89.74129%
The hypothesis that endogenous short chain fatty acids (C 6-C 10) are important in maintaining seeds of wild oat (Avena fatua L.) in the dormant state by acting as natural germination inhibitors (Berrie, Buller, Don, Parker, 1979 Plant Physiol 63: 758-764) was investigated. When germination of nondormant seeds was inhibited by treatment with short chain fatty acids, the seeds did not revert to a similar biochemical and physiological state as exhibited by dormant seeds. First, nonanoic acid-induced inhibition of seed germination was not reversed by hormone treatments which normally break dormancy in wild oat seeds. Second, nondormant seeds treated with short chain fatty acids maintained similar relative proportions of the pentose phosphate pathway and the Embden-Meyerhoff-Parnas pathway for respiratory glucose metabolism as that found in the nondormant controls. Seeds imbibed in the presence of nonanoic acid lost more amino acids and proteins into the imbibition solution than did the untreated controls, suggesting membrane damage had occurred. Inasmuch as increasing concentrations of nonanoic acid also progressively reduced the growth of the coleoptile and roots of intact seedlings until all growth ceased and no germination occurred...

‣ Contractile effect of short-chain fatty acids on the isolated colon of the rat.

Yajima, T
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1985 Português
Relevância na Pesquisa
89.858125%
The contractile effect of short-chain fatty acids on proximal, middle and distal segments of the rat colon was studied in vitro. A single contraction of the longitudinal muscle of the everted preparation of the middle and distal but not the proximal colon was induced by mucosal application of propionate, butyrate or valerate. Sigmoid dose-responses were observed between contraction and log dose of propionate, butyrate and valerate. The threshold concentration of short-chain fatty acids was between 0.02 and 0.04 mM. A maximal contraction was induced with 0.1 mM-propionate, butyrate and valerate. While acetate (up to 10 mM) and lactate (up to 30 mM) had no contractile effect at all. Serosal application of short-chain fatty acids was without effect, while the contractile response with up to 10 mM-propionate was abolished in both the middle and distal colon by scraping away the mucosa. Cumulative addition of short-chain fatty acids to the organ bath (without wash-out of the first dose) caused adaptation of the contractile response; thus, the effect of propionate (1 mM) was abolished by prior addition of acetate (10 mM) or lactate (30 mM) or propionate (1 mM) or butyrate (1 mM) or valerate (1 mM). The contractile effect of propionate was also inhibited by atropine (1 microM)...

‣ Effects of acetylcholine and short-chain fatty acids on acinar cells of the exocrine pancreas in sheep.

Katoh, K; Tsuda, T
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1984 Português
Relevância na Pesquisa
89.97662%
In order to investigate the actions of acetylcholine and short-chain fatty acids on acinar cells of the exocrine pancreas of sheep, measurements of amylase release and 45Ca efflux from superfused segments, as well as changes in membrane potential, input resistance and equilibrium potential in the acinar cells, were carried out in vitro. The application of acetylcholine or short-chain fatty acids caused a dose-dependent increase in amylase release from the superfused tissue segments. The amylase release evoked by 10(-3) M-short-chain fatty acids containing 2-8 carbon atoms increased with increasing carbon number, up to 5 (i.e. it was maximum with iso-valerate, which has 5 carbon atoms). The amylase release stimulated by acetylcholine (5.5 X 10(-6) M) or caprylate (10(-3) was accompanied by an increase in 45Ca efflux, and was significantly reduced by the removal of extracellular Ca2+. The stimulating effect of caprylate (10(-3) M) on amylase secretion was also observed in superfused segments of the guinea-pig, but not in those of the mouse, rabbit or hamster. The resting membrane potential and input resistance of acinar cells of sheep pancreas were -31.1 +/- 1.6 mV and 2.7 +/- 0.7 M omega (means +/- S.E. of means), respectively. The application of acetylcholine or short-chain fatty acids always depolarized the cell membrane and reduced the input resistance. The effect of short-chain fatty acids was observed in the presence of atropine (1.4 X 10(-6) M). The equilibrium potentials for acetylcholine and butyrate were -15.0 +/- 0.8 and -16.0 +/- 1.1 mV...

‣ Colonic fermentation of dietary fibre to short chain fatty acids in patients with adenomatous polyps and colonic cancer.

Clausen, M R; Bonnén, H; Mortensen, P B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1991 Português
Relevância na Pesquisa
89.74801%
Short chain (C2-C6) fatty acids are produced in the colon through bacterial fermentation of mainly dietary fibre. Butyrate (C4) possesses antineoplastic effects on human colon carcinoma cells, and epidemiological studies indicate that high fibre diets may reduce the incidence of colorectal cancer. The role of dietary fibre during colorectal carcinogenesis might therefore be related to its fermentation to butyrate. Faecal concentrations of total short chain fatty acids and concentrations and ratios of the individual C2-C6 fatty acids did not differ between 16 healthy controls, 17 patients with colonic adenomas, and 17 patients with colonic cancer. Comparison of the molar production velocities (mmol/l.hour) of total and individual short chain fatty acids from glucose, ispagula, wheat bran, and albumin in six and 24 hour faecal incubations showed no differences. The ratio of butyrate production to total short chain fatty acid production from fibre, however, was reduced in patients with colonic cancer and adenomas compared with healthy controls (ispagula, six hours: 6.4, 7.6, and 11.5% respectively, p = 0.005 and 24 hour: 9.1, 9.9, and 15.4%, p = 0.002; wheat bran, six hours: 9.9, 10.2, and 14.7% respectively, p = 0.06 and 24 hours: 15.1...

‣ Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

Oliveira, Ariano Jose Freitas de; Pinto Junior, Francisco Edilson Leite; Formiga, Maria Célia Carvalho; Melo, Syomara Pereira da Costa; Brandão Neto, José; Ramos, Ana Maria de Oliveira
Fonte: Universidade Federal do Rio Grande do Norte Publicador: Universidade Federal do Rio Grande do Norte
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
119.76304%
OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy; CNPq

‣ Short-chain fatty acid modulation of apoptosis in gastric and colon cancer cells.

Matthews, Geoffrey Mark
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2007 Português
Relevância na Pesquisa
98.79837%
Introduction: Gastric and colon cancer are major causes of mortality and morbidity worldwide. Gastric cancer is often detected at an advanced stage and current chemotherapeutics are only modestly effective against this neoplasm. Novel chemotherapeutics, chemopreventive agents and treatment strategies are required to prevent and treat gastric cancer. The ideal method to eliminate cancer cells may be the induction of apoptosis, further preventing cell proliferation and tumour growth. Recently, short-chain fatty acids (SCFAs) butyrate and propionate have been investigated as potential chemotherapeutic agents, particularly in colon cancer. Butyrate is reported to induce apoptosis in colon cancer cells and is demonstrated to modulate intracellular redox state by altering the levels of an antioxidant, glutathione (GSH). GSH availability is controlled by the oxidative pentose pathway (OPP). Very few studies have investigated the effects of butyrate on cell types other than colon cancer cells, and even less is known regarding the effects of propionate. This thesis investigated the potential for SCFAs to induce apoptosis in a gastric cancer cell line, Kato III, compared to the colon cancer cell line, Caco-2. Cell cycle regulation, OPP activity...

‣ Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism

Matthews, G.; Howarth, G.; Butler, R.
Fonte: Karger Publicador: Karger
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
Relevância na Pesquisa
119.03166%
BACKGROUND: Short-chain fatty acids (SCFA) are undergoing increased scrutiny as chemotherapeutics for colon cancer, although a comprehensive understanding of their mode of action is lacking. We investigated candidate SCFA for their capability to modulate apoptosis, cell cycle, intracellular redox state and glucose metabolism in the Caco-2 human colon cancer cell line. METHODS: Caco-2 cells were incubated with butyrate, propionate or a combination of these SCFA (1:1) and assessed by flow cytometry, enzyme activity analysis or by isotope ratio mass spectrometry. RESULTS: Butyrate and the SCFA combination induced apoptosis and G2-M arrest to a greater extent than propionate alone (p < 0.05). SCFA treatment led to time-dependent alterations to the oxidative pentose pathway, reductions in glutathione availability and increases in levels of reactive oxygen species (p < 0.05) compared with untreated controls. The rate of D-glucose metabolism was increased by all SCFA, although to the greatest extent by butyrate (p < 0.05). CONCLUSIONS: These results suggest that butyrate, or the combination of both SCFA, induced rapid and extensive apoptosis and G2-M arrest associated with changes to redox state and D-glucose metabolism. These results support the potential for butyrate and propionate to act as adjuncts to conventional chemotherapy regimens for colon cancer.; Matthews G.M....

‣ Medium chain fatty acids and Wnt/β-Catenin inhibitors as adjunctive colorectal cancer chemotherapeutic agents

Jane Kathryn Fauser
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2013 Português
Relevância na Pesquisa
109.9721%
Chemotherapy remains a primary treatment for advanced stage colorectal cancer (CRC). Although more targeted chemotherapeutic agents are under development, currently prescribed cytotoxic agents target rapidly-dividing cells without discrimination between neoplastic and non-neoplastic cells, inducing debilitating side-effects with high morbidity and mortality rates. The development of less injurious chemotherapeutic agents holds promise in alleviating the negative side-effects of chemotherapy. Fatty acids (FAs) are bioactive aliphatic monocarboxylic acids categorized by the number of carbon atoms in the aliphatic chain, classified as short chain fatty acids (SCFAs) (< C8:0), medium chain fatty acids (MCFAs) (C8-14:0) and long chain fatty acids (LCFAs) (>C16:ɷ3-9). Exogenous applications of FAs has demonstrated anti-neoplastic properties, and FA have been suggested as adjunctive chemotherapeutic agents for the treatment of CRC. SCFAs and LCFAs have demonstrated potent anti-neoplastic properties in in vitro models of CRC. However, there are gaps in the literature regarding the potential anti-neoplastic properties of MCFAs in CRC. Endogenous adjunctive CRC therapies manipulate signalling pathways related to the instigation and progression of CRC...

‣ Differential effects of short-chain fatty acids and iron on expression of iha in Shiga-toxigenic Escherichia coli

Herold, S.; Paton, J.; Srimanote, P.; Paton, A.
Fonte: Soc General Microbiology Publicador: Soc General Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2009 Português
Relevância na Pesquisa
108.93082%
Shiga-toxigenic Escherichia coli (STEC) colonizing the bowel are exposed to a variety of short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, produced by gut microflora. However, the total concentrations and relative amounts of SCFAs in the lumen vary with intestinal niche. Here we report that conditions simulating SCFA concentrations present in the human gut trigger expression of the iha gene, which encodes an adherence-conferring outer-membrane protein of pathogenic E. coli. We show that growth under conditions simulating colonic, but not ileal, SCFA concentrations increases iha expression in three tested STEC strains, with the strongest expression detected in LEE-negative STEC O113:H21 strain 98NK2. Expression of iha is known to be subject to Fur-mediated iron repression in O157:H7 STEC, and the same occurs in 98NK2. However, exogenous iron did not repress iha expression in the presence of colonic SCFAs in either 98NK2 or the O157:H7 strain EDL933. Moreover, exposure to the iron chelator 2,2'-dipyridyl caused no further enhancement of iha expression over that induced by colonic SCFAs. These findings indicate that SCFAs regulate iha expression in STEC independently of iron. Increased expression of iha under colonic but not ileal SCFA conditions possibly may contribute to preferential colonization of the human colon by STEC.; Sylvia Herold...

‣ Effect of short chain fatty acids on the expression of free fatty acid receptor 2 (Ffar2), Ffar3 and early-stage adipogenesis

Frost, G; Cai, Z; Raven, M; Otway, D T; Mushtaq, R; Johnston, J D
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
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Adipose tissue has a major influence on insulin sensitivity. Stimulation of free fatty acid receptor 2 (FFAR2) has been proposed to influence adipocyte differentiation. We hypothesised that exposing preadipocytes to short chain fatty acids would induce earlier expression of nuclear receptors that co-ordinate adipogenesis, triglyceride accumulation and leptin secretion. 3T3-L1 preadipocytes were differentiated in the presence of 1 μM acetate, 0.1–10 μM propionate or vehicle control. In experiment 1, expression of Ffar2 and nuclear receptor mRNA was measured by quantitative PCR over 48 h following onset of differentiation. In experiment 2, extracellular leptin concentration and intracellular triglyceride content were measured at days 0, 2, 4, 6, 8 and 10 following the onset of differentiation. Control cells exhibited similar temporal dynamics of gene expression, triglyceride accumulation and leptin secretion as reported previously. We were unable to detect expression of Ffar3 mRNA at any stage of differentiation. Consistent with a lack of Ffar2 expression in the first 24 h of differentiation, acetate and propionate had no significant effect on nuclear receptor expression. Furthermore, acetate or propionate treatment did not alter leptin concentration or triglyceride content. In conclusion...

‣ Efeito do ácido graxo de cadeia curta, acetato, nas células da microglia ativadas por lipopolissacáride (LPS).; Effect of the short chain fatty acid, acetate, on microglial cells activated by lipopolysaccharide (LPS).

Oliveira, Daniel May de
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 20/08/2015 Português
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Introdução: Ácidos graxos de cadeia curta (AGCC) são compostos que contêm de 1 a 6 átomos de carbono. Estudos mostraram que possuem efeitos imunomoduladores, antiproliferativos e pró-apoptóticos, via ativação de receptores acoplados à proteína G ou via controle epigenético, agindo na histona acetil transferase (HAT) e na histona deacetilase (HDAC). O acetato é o AGCC encontrado em maiores concentrações nos cólons e no sangue, sendo também um intermediário em diversas reações metabólicas. Apesar disso, foi pouco estudado até o momento. As células da microglia são os macrófagos residentes no sistema nervoso central e desempenham importante papel em diversas doenças. Objetivo: estudar os efeitos do acetato na microglia esclarecendo seus efeitos na produção de mediadores inflamatórios e na viabilidade celular. Conclusão: O acetato estimula a produção de TNF-α e melhora a viabilidade de culturas da microglia ativadas por LPS. A melhora da viabilidade celular ocorre pela indução de autofagia. O mecanismo responsável pela indução da autofagia é epigenético, sendo completamente independente da ativação de receptores GPR.; Introduction: short-chain fatty acids (SCFA) are compounds containing from 1 to 6 carbon atoms. Studies have shown that these compounds have immunomodulatory...

‣ Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

Oliveira, Ariano Jose Freitas de; Pinto Júnior, Francisco Edilson Leite; Formiga, Maria Célia Carvalho; Melo, Syomara Pereira da Costa; Brandao-Neto, Jose; Ramos, Ana Maria de Oliveira
Fonte: Universidade de São Paulo. Faculdade de Medicina Publicador: Universidade de São Paulo. Faculdade de Medicina
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; Formato: application/pdf
Publicado em 01/01/2010 Português
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OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy.