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Dysfunction of kidney endothelium after ischemia/reperfusion and its prevention by mitochondria-targeted antioxidant

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Abstract

One of the most important pathological consequences of renal ischemia/reperfusion (I/R) is kidney malfunctioning. I/R leads to oxidative stress, which affects not only nephron cells but also cells of the vascular wall, especially endothelium, resulting in its damage. Assessment of endothelial damage, its role in pathological changes in organ functioning, and approaches to normalization of endothelial and renal functions are vital problems that need to be resolved. The goal of this study was to examine functional and morphological impairments occurring in the endothelium of renal vessels after I/R and to explore the possibility of alleviation of the severity of these changes using mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decylrhodamine 19 (SkQR1). Here we demonstrate that 40-min ischemia with 10-min reperfusion results in a profound change in the structure of endothelial cells mitochondria, accompanied by vasoconstriction of renal blood vessels, reduced renal blood flow, and increased number of endothelial cells circulating in the blood. Permeability of the kidney vascular wall increased 48 h after I/R. Injection of SkQR1 improves recovery of renal blood flow and reduces vascular resistance of the kidney in the first minutes of reperfusion; it also reduces the severity of renal insufficiency and normalizes permeability of renal endothelium 48 h after I/R. In in vitro experiments, SkQR1 provided protection of endothelial cells from death provoked by oxygen–glucose deprivation. On the other hand, an inhibitor of NO-synthases, L-nitroarginine, abolished the positive effects of SkQR1 on hemodynamics and protection from renal failure. Thus, dysfunction and death of endothelial cells play an important role in the development of reperfusion injury of renal tissues. Our results indicate that the major pathogenic factors in the endothelial damage are oxidative stress and mitochondrial damage within endothelial cells, while mitochondria-targeted antioxidants could be an effective tool for the protection of tissue from negative effects of ischemia.

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Abbreviations

AKI:

acute kidney injury

DCF:

2,7-dichlorodihydrofluorescein

I/R:

ischemia/reperfusion

IREC:

isolated renal epithelial cells

OGD:

oxygen–glucose deprivation

ROS:

reactive oxygen species

SkQR1:

10-(6′-plastoquinonyl)decylrhodamine 19

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Authors and Affiliations

  1. Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991, Moscow, Russia

    S. S. Jankauskas, N. V. Andrianova, I. B. Alieva, A. N. Prusov, L. D. Zorova, I. B. Pevzner, D. N. Silachev, E. Y. Plotnikov & D. B. Zorov

  2. Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, 125315, Moscow, Russia

    D. D. Matsievsky

  3. Lomonosov Moscow State University, International Laser Center, 119991, Moscow, Russia

    L. D. Zorova

  4. Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, 119991, Moscow, Russia

    E. S. Savchenko

  5. Lomonosov Moscow State University, Faculty of Physics, 119991, Moscow, Russia

    Y. A. Pirogov

Authors
  1. S. S. Jankauskas
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  2. N. V. Andrianova
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  3. I. B. Alieva
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  4. A. N. Prusov
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  5. D. D. Matsievsky
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  6. L. D. Zorova
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  7. I. B. Pevzner
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  8. E. S. Savchenko
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  9. Y. A. Pirogov
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  10. D. N. Silachev
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  11. E. Y. Plotnikov
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  12. D. B. Zorov
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Corresponding authors

Correspondence to E. Y. Plotnikov or D. B. Zorov.

Additional information

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM16-208, October 24, 2016.

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Jankauskas, S.S., Andrianova, N.V., Alieva, I.B. et al. Dysfunction of kidney endothelium after ischemia/reperfusion and its prevention by mitochondria-targeted antioxidant. Biochemistry Moscow 81, 1538–1548 (2016). https://doi.org/10.1134/S0006297916120154

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  • DOI: https://doi.org/10.1134/S0006297916120154

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