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PP053-SUN EFFECT OF TRYPTOPHAN SUPPLEMENTATION ON DIET-INDUCED NON-ALCOHOLIC FATTY LIVER DISEASE IN MICE
Liver and gastrointestinal tract PP052-SUN Outstanding abstract PERIOPERATIVE PREBIOTICS, PROBIOTICS OR SYNBIOTICS FOR ELECTIVE ABDOMINAL SURGERY IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS A.H. Chowdhury1 , K.K. Varadhan1 , K. Neal2 , D.N. Lobo1 . 1 Division of Gastrointestinal Surgery, NIHR Nottingham Digestive Diseases Centre Biomedical Research Unit, 2 University of Nottingham, Nottingham, United Kingdom Rationale: Probiotics are live microorganisms, which confer beneficial effects when given in sufficient quantities. Prebiotics are nutrient substrates which enhance the effects of probiotics. When the two are given together in a single preparation they are known as synbiotics. The aim of this meta-analysis was to evaluate the effects of probiotics and synbiotics given in the perioperative period on outcome for patients undergoing abdominal surgery. Methods: Randomised controlled trials published between January 1980 and January 2013 comparing probiotics or synbiotics with a placebo or standard care (P/SC) in patients undergoing abdominal surgery were included. Postoperative outcomes were analysed using RevMan 5.1 software (Cochrane Collaboration, Denmark) and included infectious and noninfectious complications, length of hospital stay (LOS) and mortality. Subgroup analyses included probiotics vs. synbiotics and the effect of treatment duration. Results: Eighteen randomised controlled trials enrolling 1208 patients (603 receiving probiotics or synbiotics and 605 receiving P/SC) were analysed. The risk of postoperative infectious complications was reduced with both probiotics [risk ratio (RR): 0.41; 95% confidence interval (CI): 0.22 0.76; p = 0.005] and synbiotics [RR: 0.65; 95% CI: 0.48 0.86; p = 0.003], with the benefit being greater with synbiotics. Weighted metaregression did not reveal a significant relationship between infective risk and duration of probiotic or synbiotic treatment (R2 = 0.025, p = 0.452). There was a less than 1 day reduction in LOS favouring probiotic or synbiotic therapy [weighted mean difference: 0.84; 95% CI: 1.68 0.00; p = 0.05]. No significant benefit was shown for non-infectious complications or mortality. Conclusion: The risk of postoperative infectious complications is reduced with the use of probiotics and synbiotics. Disclosure of Interest: A. Chowdhury Grant/Research Support: Unrestricted research grant from Amino Up Chemical Company, Japan for unrelated work, K. Varadhan: None Declared, K. Neal: None Declared, D. Lobo Grant/Research Support: Unrestricted research grant from Amino Up Chemical Company, Japan for unrelated work
PP053-SUN Outstanding abstract EFFECT OF TRYPTOPHAN SUPPLEMENTATION ON DIETINDUCED NON-ALCOHOLIC FATTY LIVER DISEASE IN MICE Y. Ritze1 , G. B´ ardos1 , A. Hubert1 , S.C. Bischoff1 . 1 Department of Nutritional Medicine, Universitaet Hohenheim, Stuttgart, Germany Rationale: Intestinal serotonin (5-HT) metabolism is thought to play a role in gut functions by regulating gut motility, permeability, and other functions of the intestine. Here we studied the effect of tryptophan, the precursor of 5-HT,
S41 on intestinal barrier functions and non-alcoholic fatty liver disease (NAFLD). Methods: An established mouse model of NAFLD induced by fructose-enriched diet was used in this study. Tryptophan was administered orally for 8 weeks to C57BL/6J control or NAFLD mice. NAFLD-related liver parameters (hepatic triglycerides, oil-red-o staining), intestinal barrier parameters (tight junction protein occludin, portal lipopolysaccharides (LPS)) and 5-HT-related parameters (5-HT, 5-HT transporter (SERT), motility) were measured. Results: In the NAFLD group, we measured a reduced duodenal occludin protein concentration (p = 0.0007), a high portal plasma LPS level (p = 0.005) and an elevated liver to body ratio (p = 0.01) compared to the control group, respectively. TRP supplementation caused an increase in the occludin concentration (p = 0.0009), and consecutively attenuated liver to body ratio (p = 0.009) as well as hepatic fat accumulation in the NAFLD group. In addition, the NAFLD group showed reduced SERT protein expression (p = 0.002) that was normalized by TRP (p = 0.02). Conclusion: For the first time our data indicate that oral TRP supplementation attenuates experimental NAFLD in mice. The underlying mechanisms are not clear but likely involve a stabilization of the intestinal barrier in the upper small intestine and an amelioration of the dysregulated intestinal serotonergic system. Disclosure of Interest: None Declared
PP054-SUN Outstanding abstract PROTECTIVE EFFECT OF ALPHA-LIPOIC ACID IN ACUTE LIVER FAILURE OF RATS Y. Tanaka1 , M. Kaibori1 , H. Miki1 , R. Nakatake1 , M. Oishi1 , K. Tokuhara1 , M. Nishizawa2 , T. Okumura1,3 , A.-H. Kwon1 . 1 Surgery, Kansai Medical University, Hirakata, Osaka, 2 Biomedical Sciences, College of Life Sciences, 3 Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan Rationale: It is reported that cytokines and chemokines, which are produced by hepatic Kupffer cells, contribute to liver failure in patients undergoing liver surgery. Alpha-lipoic acid (a-LA) is well known as an antioxidant agent. In in vitro study, we reported that a-LA had liver-protective effects through the suppression of inducible nitric oxide synthase (iNOS) induction involved in liver injury. The aim of this study is to investigate the beneficial effects of a-LA on acute liver failure in rats induced by D-galactosamine plus lipopolysaccharide (GalN/LPS), focusing on proinflammatory cytokines and iNOS. Methods: Male Sprague-Dawly (SD) rats were treated with GalN/LPS to induce acute liver failure. a-LA was administered intraperitoneally 1 h before GalN/LPS injection. Results: A single injection of a-LA (100 mg/kg) increased the survival rate to 86% compared with GalN/LPS-treated rats (8%). a-LA prevented GalN/LPS-induced increase of serum levels of AST and ALT (liver injury marker). Histopathological analysis revealed that a-LA prevented focal hepatocyte necrosis with hemorrhagic change, ballooning degeneration and inflammatory cell infiltration in the liver. a-LA inhibited the increased concentration of proinflammatory cytokines, tumor necrosis factor (TNF)-a and interleukin (IL)-6 in serum.
PP053-SUN Outstanding abstract EFFECT OF TRYPTOPHAN SUPPLEMENTATION ON DIETINDUCED NON-ALCOHOLIC FATTY LIVER DISEASE IN MICE Y. Ritze1 , G. B´ ardos1 , A. Hubert1 , S.C. Bischoff1 . 1 Department of Nutritional Medicine, Universitaet Hohenheim, Stuttgart, Germany Rationale: Intestinal serotonin (5-HT) metabolism is thought to play a role in gut functions by regulating gut motility, permeability, and other functions of the intestine. Here we studied the effect of tryptophan, the precursor of 5-HT,
S41 on intestinal barrier functions and non-alcoholic fatty liver disease (NAFLD). Methods: An established mouse model of NAFLD induced by fructose-enriched diet was used in this study. Tryptophan was administered orally for 8 weeks to C57BL/6J control or NAFLD mice. NAFLD-related liver parameters (hepatic triglycerides, oil-red-o staining), intestinal barrier parameters (tight junction protein occludin, portal lipopolysaccharides (LPS)) and 5-HT-related parameters (5-HT, 5-HT transporter (SERT), motility) were measured. Results: In the NAFLD group, we measured a reduced duodenal occludin protein concentration (p = 0.0007), a high portal plasma LPS level (p = 0.005) and an elevated liver to body ratio (p = 0.01) compared to the control group, respectively. TRP supplementation caused an increase in the occludin concentration (p = 0.0009), and consecutively attenuated liver to body ratio (p = 0.009) as well as hepatic fat accumulation in the NAFLD group. In addition, the NAFLD group showed reduced SERT protein expression (p = 0.002) that was normalized by TRP (p = 0.02). Conclusion: For the first time our data indicate that oral TRP supplementation attenuates experimental NAFLD in mice. The underlying mechanisms are not clear but likely involve a stabilization of the intestinal barrier in the upper small intestine and an amelioration of the dysregulated intestinal serotonergic system. Disclosure of Interest: None Declared
PP054-SUN Outstanding abstract PROTECTIVE EFFECT OF ALPHA-LIPOIC ACID IN ACUTE LIVER FAILURE OF RATS Y. Tanaka1 , M. Kaibori1 , H. Miki1 , R. Nakatake1 , M. Oishi1 , K. Tokuhara1 , M. Nishizawa2 , T. Okumura1,3 , A.-H. Kwon1 . 1 Surgery, Kansai Medical University, Hirakata, Osaka, 2 Biomedical Sciences, College of Life Sciences, 3 Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga, Japan Rationale: It is reported that cytokines and chemokines, which are produced by hepatic Kupffer cells, contribute to liver failure in patients undergoing liver surgery. Alpha-lipoic acid (a-LA) is well known as an antioxidant agent. In in vitro study, we reported that a-LA had liver-protective effects through the suppression of inducible nitric oxide synthase (iNOS) induction involved in liver injury. The aim of this study is to investigate the beneficial effects of a-LA on acute liver failure in rats induced by D-galactosamine plus lipopolysaccharide (GalN/LPS), focusing on proinflammatory cytokines and iNOS. Methods: Male Sprague-Dawly (SD) rats were treated with GalN/LPS to induce acute liver failure. a-LA was administered intraperitoneally 1 h before GalN/LPS injection. Results: A single injection of a-LA (100 mg/kg) increased the survival rate to 86% compared with GalN/LPS-treated rats (8%). a-LA prevented GalN/LPS-induced increase of serum levels of AST and ALT (liver injury marker). Histopathological analysis revealed that a-LA prevented focal hepatocyte necrosis with hemorrhagic change, ballooning degeneration and inflammatory cell infiltration in the liver. a-LA inhibited the increased concentration of proinflammatory cytokines, tumor necrosis factor (TNF)-a and interleukin (IL)-6 in serum.