Mitochondrial Function in the Kidney and Heart, but Not the Brain, is Mainly Altered in an Experimental Model of Endotoxaemia

Marina Makrecka-Kuka, Stanislava Korzh, Karlis Vilks, Reinis Vilskersts, Helena Cirule, Maija Dambrova, Edgars Liepinsh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Significant impairments in mitochondrial function are associated with the development of multi-organ failure in sepsis/endotoxaemia, but the data on the dynamics of simultaneous mitochondrial impairment in multiple organs are limited. The aim of this study was to evaluate the changes in heart, brain and kidney mitochondrial function in an experimental model of lipopolysaccharide (LPS)-induced endotoxaemia.Samples were collected 4 and 24h after single injection of LPS (10mg/kg) in mice. Marked increases in inflammation-related gene expression were observed in all studied tissues 4h after LPS administration. At 24h post LPS administration, this expression of inflammation-related genes remained upregulated only in kidneys. Significantly increased concentrations of kidney function markers confirmed that kidneys were severely damaged. Echocardiographic measurements showed that the ejection fraction and fractional shortening were significantly reduced 4h after LPS administration, whereas 24h after LPS administration, the cardiac function was restored to baseline. A two-fold decrease in mitochondrial oxidative phosphorylation (OXPHOS) capacity in the kidney was observed 4 and 24h after LPS administration. Significant decrease in mitochondrial fatty acid oxidation was observed in heart 4h after LPS administration. Furthermore, 24h after LPS administration, the respiration rates in cardiac fibers at OXPHOS and electron transport (ET) states were significantly increased, which resulted in increased ET coupling efficiency in the LPS-treated group, whereas four-fold increases in the H2O2 production rate and H2O2/O ratio were observed. The brain mitochondria demonstrated a slightly impaired mitochondrial functionality just 24h after the induction of endotoxaemia.In conclusion, among studied tissues kidney mitochondria are the most sensitive to endotoxaemia and do not recover from LPS-induced damage, whereas in brain, mitochondrial function was not significantly altered. In heart, endotoxaemia induces a decrease in the mitochondrial fatty acid oxidation capacity, but during the phase of suppressed inflammatory response, the ET efficiency is improved despite the marked increase in reactive oxygen species production.

Original languageEnglish
Pages (from-to)e153-e162
JournalShock
Volume52
Issue number6
DOIs
Publication statusPublished - 1 Dec 2019

Keywords

  • Electron transfer system
  • endotoxaemia
  • inflammation
  • markers or organ damage
  • mitochondrial dysfunction
  • multi-organ failure
  • reactive oxygen species

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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