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Protective Effect of Peroxiredoxin 6 in Ischemia/Reperfusion-Induced Damage of Small Intestine

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Abstract

Background

Strong oxidative stress starting in the epithelium upon restoration of blood cell circulation is a major cause of necrosis of the intestinal epithelium in ischemia/reperfusion-induced damage.

Aim

The purpose of this study was to investigate the tissue-protective effect of exogenous peroxiredoxin 6 (Prx6) in ischemia/reperfusion-induced damage of small intestine.

Methods

The research was carried out using a model of acute superior mesenteric artery occlusion in Wistar male rats. Exogenous Prx6 was administrated intravenously 15 min prior to small intestine ischemia. The distribution of endogenous Prx6 in the small intestine was determined by immunohistochemical analysis. The expression level of antioxidant enzymes was evaluated by RT-PCR in real time.

Results

Exogenous Prx6 injected to animals intravenously was detected in blood vessel lumens, and its diffuse distribution was subsequently confirmed in the intestinal epithelium. Expression analysis of genes coding for major antioxidant enzymes demonstrated a significant activation of SOD 1, SOD 3, Prx6, GPx2, GPx7 expression during I/R-induced damage of the small intestine. Injection of exogenous Prx6 prior to induced ischemia resulted in minimization of oxidative injury by reducing necrosis and apoptosis, by normalization of gene activity of antioxidant enzyme. It eventually led to a reduction of epithelium destruction in the small intestine. By contrast, administration of a purified mutant form of Prx6 (Prx6C47S) without peroxidase activity had no protective effect.

Conclusion

The application of exogenous Prx6 enables normalization of the antioxidant status of the small intestine and reduction of cell destruction upon I/R-induced organ damage.

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Acknowledgments

The study was supported by the Russian Foundation for Basic Research (RFBR Grants Nos. 13-04-00537, 13-04-00763 and 15-04-04009) by a Grant from the Presidium of RAS “Molecular and Cell Biology.” The authors thank Dr. Victor Guzov for critical proofreading of the manuscript.

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, 3, Institutskaya, Pushchino, Moscow Region, Russia, 142290

    A. E. Gordeeva, M. G. Sharapov, E. E. Fesenko & V. I. Novoselov

  2. N.V. Sklifosovsky Research Institute for Emergency Medicine of Moscow Healthcare Department, Moscow, Russia

    A. A. Temnov

  3. Department of Structural and Computational Biology, Max. F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter 5, 1030, Vienna, Austria

    A. A. Charnagalov

Authors
  1. A. E. Gordeeva
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  2. A. A. Temnov
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  3. A. A. Charnagalov
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  4. M. G. Sharapov
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  5. E. E. Fesenko
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  6. V. I. Novoselov
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Corresponding author

Correspondence to V. I. Novoselov.

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Gordeeva, A.E., Temnov, A.A., Charnagalov, A.A. et al. Protective Effect of Peroxiredoxin 6 in Ischemia/Reperfusion-Induced Damage of Small Intestine. Dig Dis Sci 60, 3610–3619 (2015). https://doi.org/10.1007/s10620-015-3809-3

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  • DOI: https://doi.org/10.1007/s10620-015-3809-3

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