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The Protective Effect of a Chimeric PSH Antioxidant Enzyme in Renal Ischemia–Reperfusion Injury

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Abstract—A rapid increase in the concentration of free radicals and reactive oxygen species at the reperfusion stage is the most dangerous stage of ischemia–reperfusion injury. An avalanche-like increase in the level of reactive oxygen species and secondary products of free radical oxidation of biological macromolecules leads to the development of oxidative stress. The use of exogenous antioxidants can reduce the concentration of reactive oxygen species in the affected tissues and suppress or correct the course of oxidative stress; thus, it significantly reduces the severity of ischemia–reperfusion injury. Acute ischemic renal failure is one of the most important social problems in a comprehensive list of pathologies associated with ischemia–reperfusion. The nephroprotective effect of a chimeric PSH antioxidant enzyme that includes human peroxiredoxin 6 and Mn-containing superoxide dismutase of Escherichia coli has been shown on an animal model of bilateral ischemia–reperfusion renal injury. The recombinant chimeric PSH protein was able to neutralize a maximally possible wide range of reactive oxygen species due to the superoxide dismutase and peroxidase activities. It has been shown with histological, biochemical, and molecular biological methods that the preliminary administration of the chimeric PSH protein before ischemia–reperfusion significantly reduced the degree of renal tissue injury and led to a quick normalization of their structural and functional state. In addition, the administration of the PSH enzyme increased the survival of experimental animals by a factor of more than 1.5. The use of the recombinant chimeric PSH enzyme can be an effective approach in the prevention and treatment of renal ischemia–reperfusion injury, as well as for maintaining an isolated kidney during transplantation.

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Funding

The work was carried out with the financial support of The Russian Foundation for Basic Research, project nos. 17-04-00356-a and 19-04-00080-a; and the of the RAS Presidium Program Molecular and cellular biology and postgenomic technologies.

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow oblast, Russia

    R. G. Goncharov, V. I. Novoselov & M. G. Sharapov

  2. Moscow Institute of Physics and Technology, 141700, Dolgoprudny, Moscow oblast, Russia

    R. G. Goncharov, G. I. Filkov, A. V. Trofimenko, V. V. Boyarintsev, V. I. Novoselov & M. G. Sharapov

Authors
  1. R. G. Goncharov
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  2. G. I. Filkov
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  3. A. V. Trofimenko
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  4. V. V. Boyarintsev
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  5. V. I. Novoselov
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  6. M. G. Sharapov
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Corresponding author

Correspondence to M. G. Sharapov.

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CONFLICT OF INTEREST

The authors declare no conflict of interest.

COMPLIANCE WITH ETHICAL STANDARDS

The work with laboratory animals was carried out in accordance with international legal norms specified in the European Convention ETS No. 123 On the protection of vertebrate animals used for experiments or other scientific purposes [40], and the Manual on working with laboratory animals of the IBC RAS No. 57 dated 30.12.2011.

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Translated by E. Puchkov

Abbreviations: IR, ischemia–reperfusion; ROS, reactive oxygen species; PSH, Prx6-MnSOD-His-tag, a chimeric protein consisting of human peroxiredoxin 6 and Mn-containing superoxide dismutase; PCR, polymerase chain reaction, MDA, malondialdehyde.

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Goncharov, R.G., Filkov, G.I., Trofimenko, A.V. et al. The Protective Effect of a Chimeric PSH Antioxidant Enzyme in Renal Ischemia–Reperfusion Injury. BIOPHYSICS 65, 303–312 (2020). https://doi.org/10.1134/S0006350920020050

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  • DOI: https://doi.org/10.1134/S0006350920020050

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