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An integrated approach to assessing nitroso-redox balance in systemic inflammation
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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 and Medicine, Vol.51 (No.6). pp. 1137-1145. doi:10.1016/j.freeradbiomed.2011.06.012
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Official URL: http://dx.doi.org/10.1016/j.freeradbiomed.2011.06....
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. Sand 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.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Nitrosation, Endotoxins, Septicemia, Nitric oxide, Free radicals (Chemistry), Nitrogen compounds | ||||
| Journal or Publication Title: | Free Radical Biology and Medicine | ||||
| Publisher: | Elsevier Science Inc. | ||||
| ISSN: | 0891-5849 | ||||
| Official Date: | 15 September 2011 | ||||
| Dates: |
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| Volume: | Vol.51 | ||||
| Number: | No.6 | ||||
| Page Range: | pp. 1137-1145 | ||||
| DOI: | 10.1016/j.freeradbiomed.2011.06.012 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | National Institutes of Health (U.S.) (NIH), Ruth L. Kirschstein Cardiovascular Training Grant , Medical Research Council (Great Britain) (MRC), National Institute for Health Research (Great Britain) (NIHR) | ||||
| Grant number: | HL 69029 (NIH) |
Data sourced from Thomson Reuters' Web of Knowledge
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