Purine, kynurenine, neopterin and lipid peroxidation levels in inflammatory bowel disease

Forrest, Caroline M.; Youd, Philippa; Kennedy, Alan; Gould, Stuart; Darlington, L. Gail; Stone, T. W.

doi:10.1007/bf02256538

Cited by 71 publications

(35 citation statements)

References 39 publications

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“…Forrest et al [21] detected an increased level of serum KYNA in patients with inflammatory bowel disease. In contrast, a decreased plasma content of KYNA was found in patients with irritable bowel syndrome [22].…”

Section: Discussionmentioning

confidence: 98%

On the toxicity of kynurenic acid in vivo and in vitro

Turski

Małaczewska

Marciniak

et al. 2014

Pharmacological Reports

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Section: Discussionmentioning

confidence: 98%

On the toxicity of kynurenic acid in vivo and in vitro

Turski

Małaczewska

Marciniak

et al. 2014

Pharmacological Reports

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“…Patients with mild inflammatory bowel disease (Crohn's disease and ulcerative colitis) exhibited an increased level of KYNA, which may be either a compensatory response to the enhanced activation of enteric neurons, or a primary abnormality which induces a compensatory increase in gut activity (Forrest et al, 2002).…”

Section: Bowel Diseasementioning

confidence: 99%

Role of Kynurenines in the Central and Peripherial Nervous Systems

Németh¹,

Toldi²,

Vécsei

2005

CNR

154

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Kynurenine (KYN) is an intermediate in the pathway of the metabolism of tryptophan to nicotinic acid. KYN is formed in the mammalian brain (40%) and is taken up from the periphery (60%), indicating that it can be transported across the blood-brain barrier (BBB). In the brain, KYN can be converted to two other components of the pathway: the neurotoxic quinolinic acid (QUIN) and the neuroprotective kynurenic acid (KYNA). QUIN is probably the most widely studied metabolite of KYN, because it may cause excitotoxic neuronal cell loss and convulsions by interacting with the N-methyl-D-aspartate (NMDA) receptor complex, a type of glutamate receptor. KYNA is another metabolite of KYN; its synthesis is catalysed by KYN aminotransferases. This is the only known endogenous NMDA receptor inhibitor, which can act at the glycine site on the receptor complex. Furthermore, KYNA non-competitively inhibits alpha7 nicotinic acetylcholine presynaptic receptors (nAChRs), inhibiting glutamate release, and regulates the expression of alpha4beta2 nAChR. It is well-known that the activation of excitatory amino acid (EAA) receptors can play a role in a number of neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, stroke and epilepsy. Various studies have been made of whether the EAA receptor antagonist KYNA can exert a therapeutic effect in these neurological disorders. It has been established that KYNA has only a very limited ability to cross the BBB. Other KYNA derivatives have been synthesised (e.g. glucosamine-KYNA, 4-chloro-KYNA and 7-chloro-KYNA), which are well transported across the BBB and act on the glutamate receptors. Moreover, it has been demonstrated that probenecid, a known inhibitor of the transport of organic acids (e.g. KYNA), increases the cerebral concentration of KYNA. There is another new perspective to the maintenance of a high level of KYNA in the brain: the use of enzyme inhibitors, which can block the synthesis of the neurotoxic QUIN. These are some of the most promising possibilities as novel therapeutic strategies for the treatment of neurodegenerative diseases, in which the hyperactivation of amino acid receptors could be involved. The presence and importance of KYN derivatives in the periphery are also discussed in the light of recent publications.

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“…Activated lymphocytes T were proved to synthesize interferon-γ, which stimulates the release of NPT from monocytes/macrophages [5][6][7]. Previous studies confirmed the usefulness of NPT as a clinical marker of many autoimmune conditions [5,8,9], e.g., in gastroenterology [10][11][12][13], endocrinology [14], and rheumatology [15,16].…”

Section: Introductionmentioning

confidence: 90%

Clinical usefulness of serum neopterin in children with juvenile idiopathic arthritis

et al. 2015

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AbstractThe aim of this study was to analyze the usefulness of the serum concentration of neopterin (NPT) as a marker of juvenile idiopathic arthritis (JIA). The study included 67 children with JIA (36 girls and 31 boys), aged between 3.8 and 17.9 years (mean 13.7±3.4 years), and 105 healthy controls (47 girls and 58 boys) of similar age, with no evidence of acute or chronic inflammation. Serum NPT was determined immunoenzymatically. The median serum concentration of NPT and prevalence of elevated serum NPT (>11 nmol/L) were significantly higher in children with JIA than in the controls: 6.044 vs. 4.734 nmol/L (p<0.001) and 30% vs. 5% (p<0.001), respectively. The serum concentration of NPT did not correlate with body temperature (R=0.00, p=0.97), erythrocyte sedimentation rate (R=0.09, p=0.47), leukocyte count (R=−0.05, p=0.70), C-reactive protein (R=−0.14, p=0.25), and procalcitonin levels (R=0.07, p=0.56). Furthermore, serum NPT was not associated with the type of JIA. However, children with exacerbation of JIA presented with significantly higher median serum level of NPT (10.912 vs. 4.471 nmol/L, p<0.001) and higher prevalence of serum NPT >11 nmol/L (50% vs. 0%, p<0.001) than did patients with remission. These data suggest that elevated serum concentration of NPT is an accurate marker of JIA exacerbation.

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Purine, kynurenine, neopterin and lipid peroxidation levels in inflammatory bowel disease

Cited by 71 publications

References 39 publications

On the toxicity of kynurenic acid in vivo and in vitro

On the toxicity of kynurenic acid in vivo and in vitro

Role of Kynurenines in the Central and Peripherial Nervous Systems

Clinical usefulness of serum neopterin in children with juvenile idiopathic arthritis

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