Suchergebnisse

Pyruvate is a normal constituent of the body that participates in carbohydrate metabolism and functions as a scavenger of free radicals. Calcium pyruvate monohydrate (CPM) is a more stable derivative that has proved its anti-inflammatory effect in experimental colitis, among other disorders, and that could also be considered a source of calcium. Thus, it would be useful for the treatment of diseases with an inflammatory component and a high prevalence of osteoporosis like the irritable bowel syndrome (IBS). The aim of the present study is to evaluate the effects of CPM in a rat model of chronic post-inflammatory visceral pain induced by deoxycholic acid (DCA) that resembles IBS. Rats were administered DCA for three days intracolonically and then treated daily with CPM (40 and 100 mg/kg) or gabapentin (70 mg/kg) (positive control) by oral gavage for 17 days. The treatments reduced the visceral hypersensitivity measured by response to colorectal distension and referred pain. DCA induced changes in the colonic immune response characterized by increased expression of the cytokine Il-1b and the inducible enzyme Cox-2, which was reduced by the treatments. DCA also decreased the gut expression of the mucins Muc-2 and Muc-3, which was normalized by CPM, whereas gabapentin only increased significantly Muc-3. Moreover, DCA increased the expression of Tlr3, which was decreased to basal levels by all the treatments. However, the serotonin receptor Htr-4, which was also elevated, was not affected by any of the treatments, indicating no effect through this signalling pathway. In conclusion, CPM ameliorated the visceral hypersensitivity and the referred pain caused by DCA, being as effective as the control drug. Furthermore, it improved the immune status of the animals, which could contribute to the visceral analgesia and the regeneration of the intestinal epithelial barrier integrity. ; This work was supported by the Junta de Andalucía (CTS 164) and by the Spanish Ministry of Economy and Competitiveness (AGL2015-67995-C3-3-R) with funds from the European Union. The CIBER-EHD is funded by the Instituto de Salud Carlos III.

The beneficial effects of probiotics on immune-based pathologies such as inflammatory bowel disease (IBD) have been well reported. However, their exact mechanisms have not been fully elucidated. Few studies have focused on the impact of probiotics on the composition of the colonic microbiota. The aim of the present study was to correlate the intestinal anti-inflammatory activity of the probiotic Escherichia coli Nissle 1917 (EcN) in the dextran sodium sulfate (DSS) model of mouse colitis with the changes induced in colonic microbiota populations. EcN prevented the DSSinduced colonic damage, as evidenced by lower disease activity index (DAI) values and colonic weight/length ratio, when compared with untreated control mice. The beneficial effects were confirmed biochemically, since the probiotic treatment improved the colonic expression of different cytokines and proteins involved in epithelial integrity. In addition, it restored the expression of different micro-RNAs (miR-143, miR-150, miR-155, miR- 223, and miR-375) involved in the inflammatory response that occurs in colitic mice. Finally, the characterization of the colonic microbiota by pyrosequencing showed that the probiotic administration was able to counteract the dysbiosis associated with the intestinal inflammatory process. This effect was evidenced by an increase in bacterial diversity in comparison with untreated colitic mice. The intestinal anti-inflammatory effects of the probiotic EcN were associated with an amelioration of the altered gut microbiome in mouse experimental colitis, especially when considering bacterial diversity, which is reduced in these intestinal conditions. Moreover, this probiotic has shown an ability to modulate expression levels of miRNAs and different mediators of the immune response involved in gut inflammation. This modulation could also be of great interest to understand the mechanism of action of this probiotic in the treatment of IBD. ; This work was supported by the Junta de Andalucía (CTS 164) and by the Spanish Ministry of Economy and Competitiveness (SAF2011-29648 and AGL2015-67995-C3-3-R) with funds from the European Union. The funders had no role in the study design, data collection, and analysis.

Intestinal microbiota modulation is becoming an interesting approach to manage inflammatory bowel disease and can be achieved by the administration of prebiotics. Previous studies showed the intestinal anti-inflammatory effects of the prebiotic lactulose. The aim of the present study was to test the preventative effects of oligosaccharides derived from lactulose with prebiotic properties (OsLu) in the trinitrobenzenesulfonic acid model of rat colitis and compare them with those of lactulose. Both treatments modified bacterial profile in intestinal contents, increasing the bifidobacteria and lactobacilli counts and up-regulating the production of short-chain fatty acids, although OsLu generated a larger amount. OsLu also inhibited to a greater extent different pro-inflammatory markers such as interleukins (IL) 1, 6, 12, and 23 and chemokines (MCP-1 and CINC-1). However, both prebiotics equally restored colonic epithelial integrity, evaluated both with a histological score (OsLu, 9.8 ± 2.2; and lactulose, 12.1 ± 2.1, vs colitic control, 27.3 ± 3.3) and by measuring several key proteins of the mucosal barrier (MUC-2, MUC-3, and TTF-3). OsLu effect was also associated with an inhibition of iNOS expression and a reduction of Th17 cell activity in the inflamed tissue that facilitated the intestinal mucosa barrier recovery. In conclusion, OsLu showed a better anti-inflammatory profile than lactulose in this model of experimental colitis. © 2014 American Chemical Society. ; This work was supported by the Spanish Ministry of Economy and Competitivity (SAF2011-29648), by Consolider-Ingenio 2010: FUNC-C-FOOD CSD 2007-00063, and by Junta de Andalucia (AGR-6826 and CTS 164) with funds from the European Union. F.A. is a predoctoral fellow of the Junta de Andalucia; J.G.-M. is a predoctoral fellow of the Spanish Ministry of Education and Science; N.G.-M. is a postdoctoral fellow of the Ramon Areces Foundation; M.E.R.-C. is a postdoctoral fellow of CIBEREHD. CIBEREHD is funded by the Instituto de Salud Carlos III. ; Peer Reviewed

Purpose: We aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of rat colitis. Methods: Nanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically. Results: The resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone. Conclusion: Silk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects. ; This work was supported by the Spanish Ministry of Science and Innovation (grant number SAF2011-29648) with funds from the European Union, and by the Junta de Andalucia (grant numbers AGR-6826 and CTS 164). Parts of the experiments were financed by funds of the European Regional Development Fund (ERDF) Operative Program of the Region of Murcia 2007–2013. The research contract of Dr A Abel Lozano-Pérez was partially supported (at 80%) by the FEDER Operative Program of the Region of Murcia 2007–2013. F Algieri is a predoctoral fellow of the Junta de Andalucia; J Garrido-Mesa is a predoctoral fellow of the Spanish Ministry of Education, Culture and Sport; N Garrido-Mesa is a postdoctoral fellow of the Ramon Areces Foundation; ME Rodríguez-Cabezas is a postdoctoral fellow of Centro de Investigaciones Biomédicas en Red – Enfermedades Hepáticas y Digest (CIBER-EHD), which is funded by the Instituto de Salud Carlos III.

This research was funded by the FEDER-INNTERCONECTA-CDTI program (CDTI, Centre for the Development of Industrial Technology; NATURPICK Project ITC-20181038), by the Junta de Andalucia (CTS 164) and by Instituto de Salud Carlos III (PI19/01058) with funds from the European Union. T.V. is a postdoctoral fellow from Instituto de Investigacion Biosanitaria de Granada; A.J.R.-M. and L.H.-G. are predoctoral fellows from University of Granada ("Programa de Doctorado: Medicina Clinica y Salud Publica"); P.D.-E. is a postdoctoral fellow from University of Granada. The CIBER-EHD and CIBERCV are funded by the Instituto de Salud Carlos III. ; Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesityassociated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ß, Il-6, Tnf-a, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-a, Ppar-g, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome. ; FEDER-INNTERCONECTA-CDTI program (CDTI, Centre for the Development of Industrial Technology) ITC-20181038 ; Junta de Andalucia CTS 164 ; Instituto de Salud Carlos III European Commission PI19/01058 European Commission Instituto de Salud Carlos III ; European Commission