N-Methyl-d-aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat

Varga, Gabriella; Érces, Dániel; Fazekas, Borbála; Fülöp, Márta; Kovács, Tamás; Kaszaki, József; Fülöp, Ferenc; Vécsei, László; Boros, Mihály

doi:10.1111/j.1365-2982.2009.01390.x

Cited by 67 publications

(55 citation statements)

References 50 publications

(63 reference statements)

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“…Administration of MK-801 reduced the cellular content in BAL fluid and decreased the levels of pro-inflammatory cytokines through a reduction in oxidative stress. Decrease in oxidative stress in a model of acute experimental colitis was achieved by treatment with KA [37] . Administration of competitive antagonists of the NMDA receptor was tested in arthritis models induced by injection of Freund's adjuvant [38] or carrageenan [39] .…”

Section: Discussionmentioning

confidence: 99%

The N-Methyl-D-Aspartic Acid Receptor Antagonist Memantine Ameliorates and Delays the Development of Arthritis by Enhancing Regulatory T Cells

et al. 2012

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The neuroendocrine impact on rheumatoid arthritis is not yet fully described although numerous neurotransmitters are shown to act as inflammatory modulators. One of these is the excitatory transmitter glutamate (Glu). In this study, the influence of the Glu receptor (GluR)-mediated effects on collagen-induced arthritis (CIA) was investigated. CIA was induced in DBA/1 mice by immunization with chicken collagen type II (CII). Mice were exposed to the following GluR antagonists: group 1, the N-methyl-D-aspartic acid (NMDA) receptor channel blocker memantine; group 2, the metabotropic GluR antagonist AIDA, and group 3, the excitatory amino acid receptor antagonist kynurenic acid (KA). Arthritis was evaluated clinically and histologically and compared to PBS-treated controls. The effects of treatment on T cell populations and the levels of anti-CII and anti-citrullinated peptide antibodies were evaluated. Memantine treatment significantly improved the course of CIA, reducing synovitis (p = 0.007) and the frequency of erosions (p = 0.007). Memantine treatment up-regulated the expression of Foxp3 in spleen CD4+ T cells followed by an increase in CD4+CD25+ regulatory T cells. The other GluR antagonists, AIDA and KA, had no effect on CIA. These results demonstrate that blockade of the NMDA receptor channel with memantine delays and attenuates the development of arthritis, probably by promoting the development of regulatory T lymphocytes.

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Section: Discussionmentioning

confidence: 99%

The N-Methyl-D-Aspartic Acid Receptor Antagonist Memantine Ameliorates and Delays the Development of Arthritis by Enhancing Regulatory T Cells

et al. 2012

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“…The highest concentration was reported in honeybee products and some fresh vegetables including broccoli and potato [22]. Although the role of KYNA in the gastrointestinal tract is still not fully elucidated, previous studies revealed its involvement in a complex duodenal mucosa protection system [5][6][7], modulation of intestinal motility, and inflammatory response in experimental colonic obstruction in dogs [9] and experimental colitis in rats [23]. Moreover, taking into consideration that KYNA supported the growth of probiotic bacteria in vitro, its potential role in the regulation of bacterial growth in the digestive system is suggested [3].…”

Section: Introductionmentioning

confidence: 99%

Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

Walczak

Turski

Rzeski

2012

Pharmacological Reports

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Abstract:Background: Kynurenic acid (KYNA), a tryptophan metabolite, was found in the mucus of rat small intestine. However, its role in the gastrointestinal tract is still not fully elucidated. Methods: To verify whether KYNA affects cell cycle regulators, the protein expression of cyclin-dependent kinase inhibitor p21 Waf1/Cip1 was investigated in colon adenocarcinoma HT-29 cells exposed to KYNA. MTT, BrdU assay and siRNA technology were used to evaluate the effect of KYNA on cancer cell proliferation. Results: KYNA significantly enhanced the expression of p21 Waf1/Cip1. Importantly, the overexpression of this protein was involved in inhibition of proliferation and DNA synthesis in HT-29 cells. Conclusions: KYNA may be considered as a potential chemoprevention agent against colon cancer.

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“…In fact, the glutamate receptors are also present in pancreas, gut, kidney, liver, lung, spleen, and testis [35,36] . Experiments performed on bovine aorta endothelial cell cultures showed that KYNA exerted a protective activity against the homocysteine-induced impairment of endothelial cells [8] . The addition of KYNA significantly increased endothelial cell migration and proliferation, which was diminished by homocysteine.…”

Section: Discussionmentioning

confidence: 99%

“…For example, systemically administered high doses of KYNA had a neuroprotective effect in the gerbil model of global ischemia [7] . Both the homocysteine-induced impairment of endothelial cells [8] and the motility and inflammatory activation in the early phase of acute experimental colitis in the rat [9] were significantly reduced by administration of KYNA. The aim of this study was to investigate whether the heatstroke induced hypotension, systemic inflammatory responses, hypothalamic ischemia and damage, and multiorgan dysfunction could be attenuated by KYNA preconditioning.…”

mentioning

confidence: 90%

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Hsieh

Chen

Yeh³

et al. 2011

Acta Pharmacol Sin

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IntroductionHeatstroke is defined as a form of excessive hyperthermia (>40 °C) associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system (CNS) disorders such as delusion, convulsion and coma predominate [1] . Our recent results have demonstrated that heatstroke rodents display hypotension, systemic inflammatory responses, hypothalamic ischemia and neuronal damage, and multi-organ dysfunction [2][3][4] .Kynurenic acid (KYNA) or its metabolic precursor L-kynurenine may be of therapeutic value in neurodegenerative diseased models [5,6] . For example, systemically administered high doses of KYNA had a neuroprotective effect in the gerbil model of global ischemia [7] . Both the homocysteine-induced impairment of endothelial cells [8] and the motility and inflammatory activation in the early phase of acute experimental colitis in the rat [9] were significantly reduced by administration of KYNA. The aim of this study was to investigate whether the heatstroke induced hypotension, systemic inflammatory responses, hypothalamic ischemia and damage, and multiorgan dysfunction could be attenuated by KYNA preconditioning. Accordingly, the temporal profiles of the apoptotic cell numbers of spleen, kidney, liver, lung, and hypothalamus, Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke Aim: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. Methods: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 ºC for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 ºC) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. Results: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tunor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 lev...

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N-Methyl-d-aspartate receptor antagonism decreases motility and inflammatory activation in the early phase of acute experimental colitis in the rat

Cited by 67 publications

References 50 publications

The N-Methyl-<i>D</i>-Aspartic Acid Receptor Antagonist Memantine Ameliorates and Delays the Development of Arthritis by Enhancing Regulatory T Cells

The N-Methyl-<i>D</i>-Aspartic Acid Receptor Antagonist Memantine Ameliorates and Delays the Development of Arthritis by Enhancing Regulatory T Cells

Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

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