Saijo, Fumito, Milsom, Alexandra B., Bryan, Nathan S., Bauer, Selena M., Vowinkel, Thorsten, Ivanovic, Marina, Andry, Chris, Granger, D. Neil, Rodriguez, Juan and Feelisch, Martin. (2010) On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease. Nitric Oxide: Biology and Chemistry, Vol.22 (No.2). pp. 155-167. ISSN 1089-8603

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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.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Inflammatory bowel diseases -- Research, Ulcerative colitis -- Research, Biochemical markers, Nitrogen in the body, Inflammation
Journal or Publication Title:	Nitric Oxide: Biology and Chemistry
Publisher:	Elsevier
ISSN:	1089-8603
Date:	15 February 2010
Volume:	Vol.22
Number:	No.2
Page Range:	pp. 155-167
Identification Number:	10.1016/j.niox.2009.11.009
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	National Institutes of Health (U.S.) (NIH), Medical Research Council (Great Britain) (MRC)
Grant number:	HL 69029 (NIH), P20 RR16456 (NIH),
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URI:	http://wrap.warwick.ac.uk/id/eprint/3223

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