-
[show abstract]
[hide abstract]
ABSTRACT: Introduction: The consequence of inflammatory bowel diseases (IBD) is cytokine-mediated severe local tissue damage. Our aim was to determine the extent of inflammatory response and to influence the morphologic changes during the subacute phase of trinitro-benzene sulfonic acid (TNBS)-induced experimental colitis by oral phosphatidylcholine (PC) and N-methyl-D-aspartate (NMDA) receptor antagonist kynurenic acid therapy. Methods: Sprague-Dawley rats were randomized to control, untreated colitis (ic TNBS), colitis fed with 2% PC-containing diet (3 days pre-treatment +3 days treatment after TNBS induction), colitis with kynurenic acid treatment (on day 6, n = 7) groups. The colitis was characterized by tissue myeloperoxidase and plasma TNF-alpha levels, the extent of tissue damage, structural changes in microvasculature (FITC-dextran staining) and mucosal injury (acridine orange staining) were determined by in vivo confocal laser scanning endomicroscopy (Optiscan Five1, Australia) and conventional histology (hematoxyilin-eosin staining). Results: Significant elevation in myeloperoxidase and TNF-alpha levels with remarkable damage in epithelial structure was detected in the colitis group. Both treatment regimens significantly decreased the level of inflammatory activation but only PC pretreatment could preserve the number of goblet cells and the epithelial structure. Treatment with kynurenic acid did not alter the morphology changes. Conclusion: Oral PC pretreatment is a promising possibility in the therapy of IBDs through decreasing inflammatory reaction and increasing the number of goblet cells.
Magyar Sebészet (Hungarian Journal of Surgery) 08/2012; 65(4):191-7.
-
[show abstract]
[hide abstract]
ABSTRACT: Introduction: Gastrointestinal methane generation has been demonstrated in various conditions, but it is not known whether it has any impact on the mammalian physiology or pathophysiology. Our aim was to characterize the effects of exogenous methane on the process of inflammatory events induced by reoxygenation in a canine model of ischemia-reperfusion. Materials and methods: Sodium pentobarbital-anesthetized inbred beagle dogs (n = 18) were randomly assigned to sham-operated or ischemia-reperfusion (I/R) groups. I/R was induced by occluding the superior mesenteric artery for 1 h, and the subsequent reperfusion was monitored for 3 h. For 5 min before reperfusion, the animals were mechanically ventilated with normoxic artificial air with or without 2.5% methane. The macrohemodynamics and small intestinal pCO2 gap changes were recorded and tissue superoxide and nitrotyrosine levels and myeloperoxidase activity changes were determined in intestinal biopsy samples. Structural mucosal damage was measured via light microscopy and HE staining. Results: Methane inhalation positively influenced the macrohemodynamic changes, significantly reduced the intestinal pCO2 gap changes and the magnitude of the tissue damage after reperfusion. Further, the intestinal myeloperoxidase activity, the superoxide and nitrotyrosine levels were reduced. Conclusions: These data demonstrate the anti-inflammatory profile of methane. The study provides evidence that exogenous methane modulates leukocyte activation and affects key events of I/R-induced oxidative and nitrosative stress.
Magyar Sebészet (Hungarian Journal of Surgery) 08/2012; 65(4):205-11.
-
[show abstract]
[hide abstract]
ABSTRACT: We set out to investigate the time-dependent colon motility and inflammatory changes in a rodent model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in order to estimate the efficacy of N-methyl-D-aspartate (NMDA) receptor antagonist therapy administered 6 day after the acute inflammatory event. Anaesthetized Sprague-Dawley rats were randomized to control (n=6) or colitis groups (n=18). The endogenous NMDA receptor antagonist kynurenic acid (n=6) or the synthetic analog SZR-72 (n=6) was administered 6 day after TNBS induction. Large bowel motility parameters, macrohaemodynamics and serosal microcirculatory changes were recorded; the severity of colonic damage was monitored by using in vivo confocal laser endomicroscopy. Nitrite/nitrate and nitrotyrosine levels, and xanthine oxidoreductase and myeloperoxidase activities were determined on colon biopsies; plasma levels of TNF-α and IL-6 were compared with those under control and 1-day colitis (n=6) conditions. TNBS induction elevated the tissue inflammatory enzyme activities, proinflammatory cytokine release, and nitrite/nitrate and nitrotyrosine formation. The microscopic vascular and mucosal lesions were accompanied by significant increases in serosal microcirculation and frequent intestinal movements 6 day after colitis. The NMDA receptor antagonist treatments significantly decreased the signs of inflammatory activation and the levels of nitric oxide end-products, normalized the microcirculation and the rate of bowel movements in both NMDA receptor antagonist-treated colitis groups. Blockade of the enteric NMDA receptors 6 day after colitis induction concurrently influenced NO production-linked nitrosative stress and colon dysmotility and may therefore offer a possibility via which to inhibit the progression of inflammatory changes in the later phase of TNBS colitis.
European journal of pharmacology 07/2012; 691(1-3):225-34. · 2.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was designed to follow the time course of inflammatory activation in a rodent model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. We hypothesized that oral phosphatidylcholine (PC) pretreatment regimens may influence leukocyte-mediated microcirculatory reactions in this condition. In series I, Wistar rats were monitored 1 day after colitis induction (n = 24), and in series II (n = 24) on day 6 following a TNBS enema. The PC-pretreated animals received a 2% PC-enriched diet for 6 days before the TNBS enema (series I), or for 3 days before and 3 days after TNBS treatment (series II). The macrohemodynamics, serosal microcirculation (visualized by intravital videomicroscopy), colonic xanthine oxidoreductase, myeloperoxidase and nitric oxide end products, and changes in proinflammatory cytokine levels in plasma were measured. The mucosal structural injury was monitored in vivo by means of confocal laser scanning endomicroscopy. The TNBS enema induced a systemic hyperdynamic circulatory reaction with increased serosal capillary blood flow and significantly elevated colonic inflammatory enzyme activities, levels of nitric oxide production, and cytokine concentrations. Acute colitis caused disruption of the capillary network, whereas the morphologic damage was less severe in series II. The PC pretreatment protocols led to significant decreases in the serosal hyperemic reaction, the cytokine levels, and the inflammatory enzyme activities. The objective signs of tissue damage were reduced in both series, and the number of mucus-producing goblet cells in the resolving phase of colitis was increased. Dietary PC efficiently decreases the cytokine-mediated progression of inflammatory events and preserves the microvascular structure in the large intestine.
Shock (Augusta, Ga.) 05/2012; 38(2):177-85. · 2.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gastrointestinal neuroprotection involves the net effect of many mechanisms which protect the enteral nervous system and its cells from death, dysfunction or degeneration. Neuroprotection is also a therapeutic strategy, aimed at slowing or halting the progression of primary neuronal loss following acute or chronic diseases. The neuroprotective properties of a compound clearly have implications for an understanding of the mechanism of dysfunctions and for therapeutic approaches in a number of gastrointestinal diseases.This paper focused on the roles of glutamate and N-methyl-D-aspartate (NMDA) receptors in the intrinsic neuronal control of gastrointestinal motility; the consequences of inflammation on gastrointestinal motility changes; and the involvement of tryptophan metabolites (especially kynurenic acid) in the regulatory function of the enteral nervous system and the modulation of the inflammatory response. Common features in the mechanisms of action, illustrative evidence from animal models, and experimental neuroprotective therapies making use of the currently available possibilities are also discussed.Overall, the evidence suggests that gastrointestinal neuroprotection against inflammation and glutamate-induced neurotoxicity may be mediated synergistically through the blockade of NMDA receptors and the inhibition of neuronal nitric oxide synthase activity and xanthine oxidoreductase-dependent superoxide production. These components are likewise significant factors in the pathomechanism of gastrointestinal inflammatory diseases and inflammation-linked motility alterations. Inhibition of the enteric NMDA receptors by kynurenic acid or its analogues may provide a novel option via which to influence intestinal hypermotility and inflammatory processes simultaneously.
Acta Neurovegetativa 05/2011; 119(2):211-23. · 2.73 Impact Factor
