Dataset Information

Oxidative damage in clinical ischemia/reperfusion injury: a reappraisal.

ABSTRACT:

Aims

Ischemia/reperfusion (I/R) injury is a common clinical problem. Although the pathophysiological mechanisms underlying I/R injury are unclear, oxidative damage is considered a key factor in the initiation of I/R injury. Findings from preclinical studies consistently show that quenching reactive oxygen and nitrogen species (RONS), thus limiting oxidative damage, alleviates I/R injury. Results from clinical intervention studies on the other hand are largely inconclusive. In this study, we systematically evaluated the release of established biomarkers of oxidative and nitrosative damage during planned I/R of the kidney and heart in a wide range of clinical conditions.

Results

Sequential arteriovenous concentration differences allowed specific measurements over the reperfused organ in time. None of the biomarkers of oxidative and nitrosative damage (i.e., malondialdehyde, 15(S)-8-iso-prostaglandin F2?, nitrite, nitrate, and nitrotyrosine) were released upon reperfusion. Cumulative urinary measurements confirmed plasma findings. As of these negative findings, we tested for oxidative stress during I/R and found activation of the nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of oxidative stress signaling.

Innovation

This comprehensive, clinical study evaluates the role of RONS in I/R injury in two different human organs (kidney and heart). Results show oxidative stress, but do not provide evidence for oxidative damage during early reperfusion, thereby challenging the prevailing paradigm on RONS-mediated I/R injury.

Conclusion

Findings from this study suggest that the contribution of oxidative damage to human I/R may be less than commonly thought and propose a re-evaluation of the mechanism of I/R.

SUBMITTER: de Vries DK

PROVIDER: S-EPMC3717197 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Oxidative damage in clinical ischemia/reperfusion injury: a reappraisal.

de Vries Dorottya K DK Kortekaas Kirsten A KA Tsikas Dimitrios D Wijermars Leonie G M LG van Noorden Cornelis J F CJ Suchy Maria-Theresia MT Cobbaert Christa M CM Klautz Robert J M RJ Schaapherder Alexander F M AF Lindeman Jan H N JH

Antioxidants & redox signaling 20130326 6

<h4>Aims</h4>Ischemia/reperfusion (I/R) injury is a common clinical problem. Although the pathophysiological mechanisms underlying I/R injury are unclear, oxidative damage is considered a key factor in the initiation of I/R injury. Findings from preclinical studies consistently show that quenching reactive oxygen and nitrogen species (RONS), thus limiting oxidative damage, alleviates I/R injury. Results from clinical intervention studies on the other hand are largely inconclusive. In this study, ...[more]

PMID: 23305329

Similar Datasets

Project description:BackgroundHydrogen peroxide (H2O2)-induced mitochondrial oxidative damage is critical to intestinal ischemia/reperfusion (I/R) injury, and PRDX3 is an efficient H2O2 scavenger that protects cells from mitochondrial oxidative damage and apoptosis. However, the function of PRDX3 in intestinal I/R injury is unclear. The aim of this study was to investigate the precise mechanism underlying the involvement of PRDX3 in intestinal I/R injury.MethodsAn intestinal I/R model was established in mice with superior mesenteric artery occlusion, and Caco-2?cells were subjected to hypoxia/reoxygenation (H/R) for the in vivo simulation of I/R.ResultsPRDX3 expression was decreased during intestinal I/R injury, and PRDX3 overexpression significantly attenuated H/R-induced mitochondrial oxidative damage and apoptosis in Caco-2?cells. The level of acetylated PRDX3 was clearly increased both in vivo and in vitro. The inhibition of SIRTs by nicotinamide (NAM) increased the level of acetylated PRDX3 and impaired the antioxidative activity of PRDX3. Furthermore, NAM did not increase the acetylation of PRDX3 in sirtuin-3 (SIRT3)-knockdown Caco-2?cells. Importantly, PRDX3 acetylation was increased in mice lacking SIRT3, and this effect was accompanied by serious mitochondrial oxidative damage, apoptosis and remote organ damage after intestinal I/R injury. We screened potential sites of PRDX3 acetylation in the previously reported acetylproteome through immunoprecipitation (IP) experiments and found that SIRT3 deacetylates K253 on PRDX3 in Caco-2?cells. Furthermore, PRDX3 with the lysine residue K253 mutated to arginine (K253R) increased its dimerization in Caco-2?cells after subjected to 12?h hypoxia and followed 4?h reoxygenation. Caco-2?cells transfected with the K253R plasmid exhibited notably less mitochondrial damage and apoptosis, and transfection of the K253Q plasmid abolished the protective effect of PRDX3 overexpression. Analysis of ischemic intestines from clinical patients further verified the correlation between SIRT3 and PRDX3.ConclusionsPRDX3 is a key protective factor for intestinal I/R injury, and SIRT3-mediated PRDX3 deacetylation can alleviate intestinal I/R-induced mitochondrial oxidative damage and apoptosis.

Dataset Information

Oxidative damage in clinical ischemia/reperfusion injury: a reappraisal.

Aims

Results

Innovation

Conclusion

Publications

Oxidative damage in clinical ischemia/reperfusion injury: a reappraisal.

Similar Datasets

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