Increased nitric oxide synthesis in ulcerative colitis

Middleton, S; Shorthouse, M.; Hunter, John

doi:10.1016/0140-6736(93)90211-x

Cited by 315 publications

(158 citation statements)

References 7 publications

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“…It cannot be ruled out, that the ability of NO to participate in inflammatory processes could play a role in the observed secretory response to NO-synthase-inhibition. NO has been demonstrated to mediate inflammation (Ialenti et al, 1992;Middleton et al, 1993) by its cytostatic and cytotoxic properties, but its role in inflammation seems to be a dual one (Moncada & Higgs, 1993;Miller et al, 1993a,b,c). We did not measure parameters of inflammation but macroscopically we did not observe reddening of the jejunum or intraluminal haemorrhage after L-NAME-treatment as an indicator of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Significance of nitric oxide in the stimulation of intestinal fluid absorption in the rat jejunum in vivo

Schirgi‐Degen

Beubler

1995

British J Pharmacology

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1 The effects of inhibiting nitric oxide (NO)-synthase on fluid transport, mucosal cyclic GMP and cyclic AMP levels and intraluminal prostaglandin E2 (PGE2)-release were studied in a model of ligated jejunal loops of anaesthetized rats in vivo. Experiments were performed under basal conditions as well as under conditions, when net fluid secretion was induced by Escherichia coli heat stable enterotoxin a (E. coli STa) or PGE2. 2 Intravenous infusion of the NO-synthase inhibitor N0-nitro-L-arginine methyl ester (L-NAME, 0.25-50mgrkg-', 45min) dose-dependently reversed net fluid absorption to net secretion, whereas infusion of D-NAME, the inactive enantiomer of L-NAME, in corresponding doses did not influence net fluid transport. Nw-nitro-L-arginine (L-NOARG, 25 mg kg-'), another NO-synthase inhibitor, also elicited net secretion of fluid. -3 L-NAME (25 mg kg ')-induced net fluid secretion was reversed to net absorption by infusion of L-arginine (400 mg kg') or sodium nitroprusside (1 mg kg-') and s.c. administration of indomethacin (10 mg kg-'). Hexamethonium (1 mg kg-', s.c.), a ganglionic blocker and granisetron (100 gsg kg-', s.c.), a 5-HT3-receptor antagonist, did not influence L-NAME-induced net secretion. 4 Net fluid secretion induced by intraluminal instillation of E. coli STa (10 units ml-') was enhanced by infusion of L-NAME (25mgkg-') and was inhibited by infusion of L-arginine (400mgkg-') and sodium nitroprusside (1 mg kg-'). D-Arginine (400 mg kg-') did not influence E. coli STa-induced fluid secretion. Likewise, net fluid secretion induced by i.a. infusion of PGE2 (79 ng ml-, 30 min) was enhanced by infusion of L-NAME and was inhibited by L-arginine and sodium nitroprusside. D-Arginine (400 mg kg-') did not influence PGE2-induced fluid secretion. 5 PGE2 levels in intraluminal fluid were not elevated after infusion of L-NAME (25mgkg-') compared to controls. 6 Mucosal cyclic GMP and cyclic AMP levels after L-NAME-treatment were not different from control values. 7 These results indicate that nitric oxide plays an important role in the regulation of intestinal fluid transport. The data suggest a nitric oxide-dependent proabsorptive tone in the intestine, which possibly involves the enteric nervous system and suppression of prostaglandin formation. This proabsorptive tone also may downregulate fluid secretion induced by E. coli STa or PGE2.

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Section: Discussionmentioning

confidence: 99%

Significance of nitric oxide in the stimulation of intestinal fluid absorption in the rat jejunum in vivo

Schirgi‐Degen

Beubler

1995

British J Pharmacology

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“…The expression of iNOS expression and nitro tyrosine accumulation (marker of peroxynitrite, the product of NO and superoxide) in inflamed mucosa of patients with ulcerative colitis and gastritis demonstrate the production of NO and its potential involvement in the pathogenesis of these diseases (Middleton et al, 1993). Studies in experimental models of CRC indicate that AOM-induced colon tumors have higher expression and/or activity of iNOS compared to levels found in adjacent colonic tissue (Takahashi et al, 1997;Rao et al, 1998).…”

Section: Inducible Nitric Oxide Synthase and Colon Cancermentioning

confidence: 99%

Dietary Non-nutritive Factors in Targeting of Regulatory Molecules in Colorectal Cancer: An Update

Pandurangan

Esa²

2013

Asian Pacific Journal of Cancer Prevention

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Colorectal cancer (CRC), a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation, and programmed cell death, is the third most common malignant neoplasm worldwide. A number of promising targets such as inducible nitric acid (iNOS), cyclooxygenase (COX)-2, NF-E2-related factor 2 (Nrf2), Wnt/β-catenin, Notch and apoptotic signaling have been identified by researchers as useful targets to prevent or therapeutically inhibit colon cancer development. In this review article, we aimed to explore the current targets available to eliminate colon cancer with an update of dietary and non-nutritional compounds that could be of potential use for interaction with regulatory molecules to prevent CRC.

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“…The disorder is characterized by immune activated state where Inducible nitric oxide synthase (iNOS) level is increased in tissues like macrophages, splenic and renal tissues and consequently NO production [32]. Induction of iNOS occurs is response to cytokine production which is a non-specific event occurring in a wide variety of conditions like ulcerative colitis [33], psoriasis [34], arthritis [35], etc. Increased production of NO is not specific for SLE rather it represent an activated state of immune system.…”

Section: Direct Effect Of Nomentioning

confidence: 99%

Biochemistry of Nitric Oxide

2011

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Nitric oxide (NO) a free radical having both cytoprotective as well as tumor promoting agent is formed from L-arginine by converting it to L-citrulline via nitric oxide synthase enzymes. The reaction product of nitric oxide with superoxide generates potent oxidizing agent, peroxynitrite which is the main mediator of tissue and cellular injury. Peroxynitrite is reactive towards many biomolecules which includes amino acids, nucleic acid bases; metal containing compounds, etc. NO metabolites may play a key role in mediating many of the genotoxic/ carcinogenic effects as DNA damage, protein or lipid modification, etc. The basic reactions of nitric oxide can be divided as direct effect of the radical where it alone plays a role in either damaging or protecting the cell milieu and an indirect effect in which the byproducts of nitric oxide formed by convergence of two independent radical generating pathways play the role in biological reactions which mainly involve oxidative and nitrosative stress. Nitric oxide is also capable of directly interacting with mitochondria through inhibition of respiration or by permeability transition. Reaction of nitric oxide with metal ions include its direct interaction with the metals or with oxo complexes thereby reducing them to lower valent state. Excessive production of nitric oxide can be studied by inhibiting the synthetic pathway of nitric oxide using both selective or specific nitric oxide synthase inhibitor or nonselective nitric oxide synthase inhibitor with respect to isoforms of nitric oxide.Keywords Nitric oxide Á Nitric oxide synthase Á Nitric oxide inhibitors Á Generation of nitric oxide Á Cancer Á Systemic lupus erythematosus Á Direct and indirect effect of nitric oxide Á Effect of nitric oxide on mitochondria

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Increased nitric oxide synthesis in ulcerative colitis

Cited by 315 publications

References 7 publications

Significance of nitric oxide in the stimulation of intestinal fluid absorption in the rat jejunum in vivo

Significance of nitric oxide in the stimulation of intestinal fluid absorption in the rat jejunum in vivo

Dietary Non-nutritive Factors in Targeting of Regulatory Molecules in Colorectal Cancer: An Update

Biochemistry of Nitric Oxide

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