Location of Repository

On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease

By Fumito Saijo, Alexandra B. Milsom, Nathan S. Bryan, Selena M. Bauer, Thorsten Vowinkel, Marina Ivanovic, Chris Andry, D. Neil Granger, Juan Rodriguez and Martin Feelisch

Abstract

Nitrite and nitrate are frequently used surrogate markers of nitric oxide (NO) production. Using rat models of acute and chronic DSS-induced colitis we examined the applicability of these and other NO-related metabolites, in tissues and blood, for the characterization of inflammatory bowel disease. Global NO dynamics were assessed by simultaneous quantification of nitrite, nitrate, nitroso and nitrosyl species over time in multiple compartments. NO metabolite levels were compared to a composite disease activity index (DAI) and contrasted with measurements of platelet aggregability, ascorbate redox status and the effects of 5-aminosalicylic acid (5-ASA). Nitroso products in the colon and in other organs responded in a manner consistent with the DAI. In contrast, nitrite and nitrate, in both intra- and extravascular compartments, exhibited variations that were not always in step with the DAI. Extravascular nitrite, in particular, demonstrated significant temporal instabilities, ranging from systemic drops to marked increases. The latter was particularly evident after cessation of the inflammatory stimulus and accompanied by profound ascorbate oxidation. Treatment with 5-ASA effectively reversed these fluctuations and the associated oxidative and nitrosative stress. Platelet activation was enhanced in both the acute and chronic model. Our results offer a first glimpse into the systemic nature of DSS-induced inflammation and reveal a greater complexity of NO metabolism than previously envisioned, with a clear dissociation of nitrite from other markers of NO production. The remarkable effectiveness of 5-ASA to abrogate the observed pattern of nitrite instability suggests a hitherto unrecognized role of this molecule in either development or resolution of inflammation. Its possible link to tissue oxygen consumption and the hypoxia that tends to accompany the inflammatory process warrants further investigation.\ud \u

Topics: R1, RC
Publisher: Elsevier
Year: 2010
OAI identifier: oai:wrap.warwick.ac.uk:3223

Suggested articles

Preview

Citations

  1. 5-aminosalicylic acid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease. doi
  2. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice.
  3. Altered ascorbic acid status in the mucosa from inflammatory bowel disease patients. Free Radic Res;22:131-43;1995. doi
  4. An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate. doi
  5. and heme-nitros(yl)ation in biological tissues and fluids: implications for the fate of NO in vivo. doi
  6. Bacteriological studies of experimental ulcerative colitis.
  7. (2009). but not cystathionine-gamma-lyase, is associated with dextran sulfate sodium-evoked colitis in mice: a sign of impaired colonic sulfide detoxification? Toxicology 264:96-103; doi
  8. Cellular targets and mechanisms of nitros(yl)ation: an insight into their nature and kinetics in vivo. doi
  9. Circulating and excretory nitrite and nitrate as indicators of nitric oxide synthesis in humans: methods of analysis. doi
  10. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest;69:238-49;1993.
  11. Combination therapy of pentoxifylline and TNFalpha monoclonal antibody in dextran sulphate-induced mouse colitis. Aliment Pharmacol Ther;13:251-60;1999. doi
  12. Comparison of methods for determination of ascorbic acid in animal tissues. Anal Chem;55:1229-32;1983. doi
  13. Confirmation of nitric oxide Saijo et. al. NO metabolites in IBD/NOX-09-99-R1 synthesis in active ulcerative colitis by infra-red diode laser spectroscopy. doi
  14. (2009). Dermal Nitrite Application Enhances Global Nitric Oxide Availability: New Therapeutic Potential for Immunomodulation? J Invest Dermatol. doi
  15. Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clin Chim Acta;274:177-88;1998. doi
  16. Differential rapid analysis of ascorbic acid and ascorbic acid 2-sulfate by dinitrophenylhydrazine method. doi
  17. Distribution of inducible nitric oxide synthase in ulcerative colitis.
  18. (2004). Dual role of endogenous nitric oxide in development of dextran sodium sulfate-induced colitis in rats. doi
  19. Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. doi
  20. Effects of aminosalicylates and immunosuppressive agents on nitric oxide-dependent N-nitrosation reactions. doi
  21. Effects of diet on measurement of nitric oxide metabolites. Clin Exp Pharmacol Physiol;24:418-20;1997. doi
  22. Efficacy of use of colonoscopy in dextran sulfate sodium induced ulcerative colitis in rats: the Saijo et. al. NO metabolites in IBD/NOX-09-99-R1 evaluation of the effects of antioxidant by colonoscopy. doi
  23. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease. doi
  24. Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. doi
  25. Expression of nitric oxide synthase in ulcerative colitis. doi
  26. Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease. doi
  27. Extraintestinal manifestations in inflammatory bowel disease. doi
  28. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. doi
  29. Hydrogen sulfide and the vasculature: a novel vasculoprotective entity and regulator of nitric oxide bioavailability? doi
  30. Hypoxia and gastrointestinal disease. doi
  31. Immunopharmacology of 5-aminosalicylic acid and of glucocorticoids in the therapy of inflammatory bowel disease.
  32. Impact of dextran sulfate sodium load on the severity of inflammation in experimental colitis. Dig Dis Sci;49:556-64;2004. doi
  33. Increased aggregation response of platelets in patients with inflammatory bowel disease. doi
  34. Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis. doi
  35. Increased luminal nitric oxide in inflammatory bowel disease as shown with a novel minimally invasive method. doi
  36. Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn's disease. Dig Dis Sci;42:1047-54;1997. doi
  37. Inducible nitric oxide synthase activity in colon biopsies from inflammatory areas: correlation with inflammation intensity in patients with ulcerative colitis but not with Crohn's disease. Amino Acids;18:229-37;2000. doi
  38. Inflammatory bowel disease stimulates formation of carcinogenic N-nitroso compounds. doi
  39. (2005). Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma.
  40. Intragastric nitric oxide production in humans: measurements in expelled air. doi
  41. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? doi
  42. Mammalian nitric oxide synthases. Adv Enzymol Relat Areas Mol Biol;65:287-346;1992. doi
  43. Mean platelet volume: a useful marker of inflammatory bowel disease activity. doi
  44. Modulation of the effect of dextran sulfate sodium-induced acute colitis by the administration of different probiotic strains of Lactobacillus and Bifidobacterium. Dig Dis Sci;49:320-7;2004. doi
  45. (2009). Myocardial protection by nitrite. Cardiovasc Res. doi
  46. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. doi
  47. Nitric oxide and superoxide: interference with hypoxic signaling. Cardiovasc Res. doi
  48. Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved doi
  49. (2009). Nitric Oxide, Cytochrome C Oxidase, and the Cellular Response to Hypoxia. Arterioscler Thromb Vasc Biol.
  50. (2009). Nitrite as regulator of hypoxic signaling in mammalian physiology. Med Res Rev. doi
  51. Nitrite from inflammatory cells--a cancer risk factor in ulcerative colitis? Dis Colon Rectum;33:1034-6;1990. doi
  52. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. doi
  53. Nitrite uptake and metabolism and oxidant stress in human erythrocytes.
  54. NK-1 antagonist reduces colonic inflammation and oxidative stress in dextran sulfate-induced colitis in rats.
  55. NO-dependent protein nitration: a cell signaling event or an oxidative inflammatory response? Trends Biochem Sci;28:646-54;2003. Saijo et. doi
  56. Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. doi
  57. Oxidation and nitrosation of thiols at low micromolar exposure to nitric oxide. Evidence for a free radical mechanism. doi
  58. (2006). Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia. Exp Physiol.;91:807-19; doi
  59. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med;35:790-6;2003. doi
  60. Platelets circulate in an activated state in inflammatory bowel disease.
  61. Platelets in inflammatory bowel disease: clinical, pathogenic, and therapeutic implications. doi
  62. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models.
  63. Resolving the nitric oxide paradox in acute tissue damage. doi
  64. Role of blood- and tissue-associated inducible nitric-oxide synthase in colonic inflammation. doi
  65. (2008). Roles of nitric oxide (NO) and NO synthases in healing of dextran sulfate sodium-induced rat colitis. doi
  66. Signal transduction by reactive oxygen species in non-phagocytic cells. doi
  67. T cell transfer model of chronic colitis: concepts, considerations, and tricks of the trade. doi
  68. The anti-oxidant properties of 5-aminosalicylic acid. Free Radic Biol Med;21:367-73;1996. doi
  69. (2008). The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. doi
  70. (2008). Therapeutic uses of inorganic nitrite and nitrate: from the past to the future. doi
  71. Thromboembolism--an important manifestation of inflammatory bowel disease. doi
  72. Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats. doi
  73. Vascular complications of inflammatory bowel disease. Mayo Clin Proc;61:140-5;1986. doi
  74. Venous thromboembolism in inflammatory bowel disease. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.