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Kidney cell death in inflammation: The role of oxidative stress and mitochondria

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Pyelonephritis is an infectious disease, and common treatment strategy is based on antibiotic therapy directed at the elimination of a pathogen. However, urinary tract infections are accompanied by inflammation and oxidative stress, which are major damaging factors, and therefore can serve as a target for therapeutic intervention. The goal of this study was to clarify the role of the mitochondrial reactive oxygen species (ROS) in kidney cell damage under experimental pyelonephritis. We investigated the mechanisms of inflammation and the role of mitochondria and oxidative stress in inflammation in kidney tissue using in vivo and in vitro models of pyelonephritis. We observed the development of oxidative stress in renal tubular epithelium in vitro, and resulting apoptotic cell death. This oxidative damage was caused by the leukocytes producing ROS after interaction with bacterial antigens. The essential role of mitochondria-mediated oxidative stress was confirmed using an experimental model of pyelonephritis in vivo. We revealed increased levels of malonic dialdehyde in kidneys of rats with experimental pyelonephritis that pointed to lipid peroxidation. Besides, high ROS levels were observed in blood leukocytes from rats with pyelonephritis. The mitochondria-targeted antioxidant SkQ1 significantly reduced the signs of kidney inflammatory injury, in particular the infiltration of neutrophils. Summarizing the data obtained, we assume the importance of mitochondrial ROS in different phases of acute pyelonephritis onset. Protection of kidney cells from infection-mediated damage can be attained by the induction of tolerance mechanisms and by antioxidant treatment.

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Abbreviations

ROS:

reactive oxygen species

DCF:

2,7-dichlorofluorescein

MPO:

myeloperoxidase

OPD:

orthophenylenediamine

DPI:

diphenyleniodonium

MDA:

malondialdehyde

TNF:

tumor necrosis factor

SkQ1:

10-(6′-plastoquinonyl)-decyltriphenyl phosphonium

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Authors and Affiliations

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

    M. A. Morosanova & I. B. Pevzner

  2. Mitoengineering Research Institute, Moscow Lomonosov State University, Moscow, 119991, Russia

    M. A. Morosanova, E. Yu. Plotnikov, I. B. Pevzner, L. D. Zorova & D. B. Zorov

  3. Belozersky Institute of Physico-chemical Biology, Moscow Lomonosov State University, Moscow, 119991, Russia

    E. Yu. Plotnikov & D. B. Zorov

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

    L. D. Zorova

Authors
  1. M. A. Morosanova
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  2. E. Yu. Plotnikov
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  3. I. B. Pevzner
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  4. L. D. Zorova
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  5. D. B. Zorov
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Correspondence to D. B. Zorov.

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Original Russian Text © M.A. Morosanova, E.Yu. Plotnikov, I.B. Pevzner, L.D. Zorova, D.B. Zorov, 2013, published in Biologicheskie Membrany, 2013, Vol. 30, No. 5–6, pp. 445–454.

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Morosanova, M.A., Plotnikov, E.Y., Pevzner, I.B. et al. Kidney cell death in inflammation: The role of oxidative stress and mitochondria. Biochem. Moscow Suppl. Ser. A 8, 103–110 (2014). https://doi.org/10.1134/S1990747813050115

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  • DOI: https://doi.org/10.1134/S1990747813050115

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