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An integrated approach to assessing nitroso-redox balance in systemic inflammation

Dyson, Alex, Bryan, Nathan S, Fernandez, Bernadette O, Garcia-Saura, Maria-Francisca, Saijo, Fumito, Mongardon, Nicolas, Rodriguez, Juan, Singer, Mervyn and Feelisch, Martin (2011) An integrated approach to assessing nitroso-redox balance in systemic inflammation Free Radical Biology & Medicine, 51, (6), pp. 1137-1145. (doi:10.1016/j.freeradbiomed.2011.06.012). (PMID:21718783).

Record type: Article

Abstract

Most studies examining the metabolic fate of NO during systemic inflammation have focused on measuring the quantitatively predominating, stable anions nitrite and nitrate within the circulation. However, these are not necessarily the NO-related products that govern NO metabolism and signaling in tissues. We assessed all major NO derivatives temporally in blood and vital organs during inflammation and explored their relationship to insult severity and redox status. Male rats receiving intraperitoneal endotoxin or vehicle were sacrificed for organ and blood sampling between 0 and 24 h. Endotoxin induced transient and organ-specific changes in a variety of NO metabolites. Nitrite and nitrate increased, peaking at 8 and 12 h, respectively. S- and N-nitrosation and heme-nitrosylation products also peaked at 8 h; these posttranslational protein modifications were associated with decreased myocardial function (echocardiography). Evidence of oxidative stress and systemic inflammation was also obtained. The rise in most NO derivatives was proportional to insult severity. All metabolite levels normalized within 24 h, despite evidence of persisting myocardial dysfunction and clinical unwellness. Our findings point to a complex interplay between NO production, antioxidant defense, and redox status. Although the precise (patho)physiologic roles of specific NO derivatives and their diagnostic/prognostic utility await further investigation, nitroso species in erythrocytes are the most sensitive markers of NO in systemic inflammation, detectable before clinical symptoms manifest.

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More information

e-pub ahead of print date: 14 June 2011
Published date: 15 September 2011
Keywords: nitrite, nitric oxide, sepsis, endotoxin, nitrosation, nitrosylation, free radicals
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337692
URI: http://eprints.soton.ac.uk/id/eprint/337692
ISSN: 0891-5849
PURE UUID: e3aa7540-7a54-49b3-b1a2-d3ce7668ec17
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 02 May 2012 12:45
Last modified: 18 Jul 2017 06:01

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Contributors

Author: Alex Dyson
Author: Nathan S Bryan
Author: Bernadette O Fernandez
Author: Maria-Francisca Garcia-Saura
Author: Fumito Saijo
Author: Nicolas Mongardon
Author: Juan Rodriguez
Author: Mervyn Singer
Author: Martin Feelisch ORCID iD

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