Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis

Miller, Mark J.S.; Thompson, Jane H.; Zhang, Xiaojing; Sadowska-Krowicka, H; Kakkis, Jane L.; Munshi, Upender K.; Sandoval, Manuel; Rossi, Janet L.; Eloby-Childress, Sandra; Beckman, Joseph S.; Ye, Yao Zu; Rodi, Charles P.; Manning, Pamela T.; Currie, Mark G.; Clark, David A.

doi:10.1016/0016-5085(95)90633-9

Cited by 282 publications

(181 citation statements)

References 28 publications

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“…In our study it is therefore unlikely that increased levels of NO, as has been shown to occur in patients with in¯ammatory bowel disease and in animal models of in¯ammation (Rachmilewitz et al, 1995;Miller et al, 1995;Singer et al, 1996) induced by iNOS, downregulate nNOS expression. Furthermore such a mechanism does not explain the loss of purinergic and adrenergic innervation.…”

Section: British Journal Of Pharmacology Vol 135 (8)mentioning

confidence: 63%

Generalized loss of inhibitory innervation reverses serotonergic inhibition into excitation in a rabbit model of TNBS‐colitis

Depoortere¹,

Thijs²,

Peeters³

2002

British J Pharmacology

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1 In¯ammation may a ect subpopulations of neurons of the myenteric plexus. 2 In the present study the e ect of trinitrobenzene sulphonic acid (TNBS) induced colitis on nitrergic, purinergic and adrenergic inhibitory neurotransmission was studied as well as the consequences of the related changes on the response of 5-HT agonists using these neurotransmitters to mediate their e ect. 3 Strips from normal and colitis rabbits (135 mg kg 71 TNBS) were subjected to electrical ®eld stimulation (EFS, 0.3 ms, 6V, 0.5 ± 32 Hz, 10 s train). The response was measured isometrically in the absence or presence of L-NAME, suramin, guanethidine, the 5-HT agonists (5-HT 1/5A/7 : 5-carboxamidotryptamine (5-CT), 5-HT 2 : a-methyl-5-HT, 5-HT 3 : 2-methyl-5-HT, 5-HT 4 : 5-methoxytryptamine (5-MeOT)) or a combination. 4 In normal strips L-NAME (1 ± 32 Hz), suramin (0.5 ± 2, 8 Hz) and guanethidine (4, 16, 32 Hz) increased the response to EFS. This e ect was abolished in in¯amed strips and was accompanied by a decrease in nNOS expression. 5 In normal strips all 5-HT agonists induced pronounced (5-CT, a-methyl-5-HT) or small (2-methyl-5-HT, 5-MeOT) inhibitory neural responses. In in¯amed strips this was reversed to cholinergic excitatory responses.6 The e ect of in¯ammation on the 5-HT 4 response was mimicked by preincubation of normal strips with L-NAME or suramin. Accordingly, in in¯amed strips L-NAME or suramin did not a ect the excitatory e ects of 5-MeOT. 7 TNBS-colitis abolishes nitrergic, purinergic and adrenergic neurotransmission. This reverses serotonergic inhibition into excitation.

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Section: British Journal Of Pharmacology Vol 135 (8)mentioning

confidence: 63%

Generalized loss of inhibitory innervation reverses serotonergic inhibition into excitation in a rabbit model of TNBS‐colitis

Depoortere¹,

Thijs²,

Peeters³

2002

British J Pharmacology

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“…32 We and others have demonstrated the contributions of reactive nitrogen oxides to in¯ammatory bowel disease and gastritis. 33,34 Indeed these species may be critical components in the development of gastritis and gastric cancer in response to Helicobacter pylori infection which is endemic in South America. 35,36 The second mechanism by which cat's claw may afford bene®t appears to be unique amongst natural products.…”

Section: Discussionmentioning

confidence: 99%

Antiinflammatory actions of cat’s claw: the role of NF‐κB

Sandoval-Chacon¹,

Thompson²,

Zhang³

et al. 1998

Aliment Pharmacol Ther

108

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Background: Uncaria tomentosa is a vine commonly known as cat’s claw or ‘uña de gato’ (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. Purpose: The aim of this study was to determine the proposed anti‐inflammatory properties of cat’s claw. Specifically: (i) does a bark extract of cat’s claw protect against oxidant‐induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events. Methods: Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 μM). Gene expression of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF‐κB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL). Results: The administration of UG (100 μg/mL) attenuated (P < 0.05) peroxynitrite‐induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat’s claw inhibited lipopolysaccharide‐induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF‐κB. Cat’s claw markedly attenuated indomethacin‐enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression. Conclusions: Cat’s claw protects cells against oxidative stress and negated the activation of NF‐κB. These studies provide a mechanistic evidence for the widely held belief that cat’s claw is an effective anti‐inflammatory agent.

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“…The colon was removed, freed from surrounding tissues, opened along the antimesenteric border, rinsed, weighed, and processed for histology and immunohistochemistry. Colon damage (macroscopic damage score) was evaluated and scored by two independent observers as described previously [28][29][30] according to the following criteria: 0, no damage; 1, localized hyperemia without ulcers; 2, linear ulcers with no significant inflammation; 3, linear ulcers with inflammation at one site; 4, two or more major sites of inflammation and ulceration extending 41 cm along the length of the colon; and 5-8, one point is added for each centimeter of ulceration beyond an initial 2 cm.…”

Section: Induction Of Experimental Colitismentioning

confidence: 99%

Role of endogenous and exogenous ligands for the peroxisome proliferators activated receptors alpha (PPAR-α) in the development of inflammatory bowel disease in mice

Cuzzocrea

Paola

Mazzon

et al. 2004

Laboratory Investigation

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The peroxisome proliferator-activated receptor-a (PPAR-a) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid and thyroid hormone receptors. The aim of the present study was to examine the effects of endogenous and exogenous PPAR-a ligand on the development of experimental colitis. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). When compared to DNBS-treated PPAR-a wild-type (WT) mice, DNBStreated PPAR-a knockout mice (PPAR-aKO) mice experienced a higher rate of the extent and severity of the histological signs of colon injury. After administration of DNBS PPAR-aWT mice experienced hemorrhagic diarrhea, weight loss and large areas of necrosis in the mucosa of the colon were also observed. Neutrophil infiltration was associated with upregulation of ICAM-1. Immunohistochemistry for nitrotyrosine showed an intense staining in the inflamed colon. Absence of a functional PPAR-a gene in PPAR-aKO mice resulted in a significant augmentation of all the above-described parameters. On the contrary, the treatment of PPAR-aWT with Wy-14643 (1 mg/kg daily i.p) significantly reduced: (i) the degree of hemorrhagic diarrhea and weight loss, (ii) the degree of colon injury, (iii) the rise in MPO activity (mucosa), (iv) the increase in staining (immunohistochemistry) for nitrotyrosine, as well as (v) the upregulation of ICAM-1 caused by DNBS in the colon. In order to elucidate whether the protective effects of Wy-14643 is related to activation of the PPAR-a receptor, we also investigated the effect the of Wy-14643 treatment on PPAR-a-deficient mice. The absence of the PPAR-a receptor significantly abolished the protective effect of the PPAR-a agonist against DNBS-induced colitis. Thus, endogenous and exogenous PPAR-a ligands reduce the degree of colitis caused by DNBS. We propose that PPAR-a ligand may be useful in the treatment of inflammatory bowel disease.

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Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis

Cited by 282 publications

References 28 publications

Generalized loss of inhibitory innervation reverses serotonergic inhibition into excitation in a rabbit model of TNBS‐colitis

Generalized loss of inhibitory innervation reverses serotonergic inhibition into excitation in a rabbit model of TNBS‐colitis

Antiinflammatory actions of cat’s claw: the role of NF‐κB

Role of endogenous and exogenous ligands for the peroxisome proliferators activated receptors alpha (PPAR-α) in the development of inflammatory bowel disease in mice

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