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Peritoneal Inflammation in Pigs is Associated with Early Mitochondrial Dysfunction in Liver and Kidney

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Abstract

The objective of this study was to investigate early effects of peritoneal inflammation on the mitochondrial function in the vital organs, liver and kidney, and their relation to inflammatory and oxidative stress mediators. The study was performed on 14 domestic pigs. Peritoneal inflammation was induced in anesthetized pigs after a midline laparotomy by autologous feces. Fluid resuscitation maintained a MAP above 60 mmHg. Animals were sacrificed 12 h later, and tissue samples were obtained to determine mitochondrial function, mRNA levels of relevant genes [inducible NO synthase (iNOS), inducible HO (HO-1), tumor necrosis factor-alpha (TNF-alpha)], generation of reactive oxygen species (ROS), and HO-1 activity. We found impaired mitochondrial function in both liver and kidney, based on decreased state 3 respiration in the liver and increased states 2 and 4 respiration in the kidney at 12 h. This was accompanied by increased TNF-alpha protein in the blood and up-regulation of TNF-alpha mRNA in the liver. Free iron was elevated in the liver but not in the kidney. In the kidney, mitochondrial ROS production was increased. Nitric oxide levels in blood remained unchanged, corresponding to unchanged levels of iNOS mRNA expression in liver and kidney. Similarly, HO-1 mRNA and heme oxygenase (HO)-activity were unchanged. The inflammatory response in the absence of characteristic septic symptoms was not associated with morphological organ damage at this early time point. Peritoneal inflammation in pigs caused mitochondrial dysfunction in liver and kidney, preceding signs of organ damage. We did not find proof that mitochondrial dysfunction was due to increased levels of either nitric oxide (NO) or products of HO, but it was accompanied by increased levels of oxidative stress markers.

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Acknowledgement

The authors wish to thank Christina Piskernik, Anna Khadem, Zafar Khakpour, Karl Kropik, Tatjana Morton, Richard Kellner, and Sabine Vagac for their expert technical assistance with the experiments, as well as Sophia Ostermeier, Kim Erwes, and Lisa Landskron, all students at the Veterinary University Vienna, for their skilled technical assistance in determining the heme oxygenase activity in tissue samples. There were no external funding sources supporting this study.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

A. V. K. designed the study and wrote the manuscript; E. C. performed the surgical part of the experiment and contributed to the manuscript; E. G. supervised data analysis and developed the instrument for high-resolution respirometry; I. K. established and performed the ROS assay, analyzed the data, and made figures; H. R. designed the study and contributed to the manuscript; J. C. D. supervised data analysis and contributed to the manuscript; M. v. G. designed the study, supervised the experiment, and contributed to the manuscript; M. J. established and performed the immunoassays, analyzed the data, and made figures; P. R. designed the study and contributed to the manuscript; R. T. H. established and performed the RT-PCR, analyzed the data, and made figures; S. B. wrote the manuscript, designed the study, and supervised the experiment; S. H. established and performed the high-resolution respirometry, analyzed the data, and made figures; T. E. established and performed the EPR-based free iron assay, analyzed the data, and made figures.

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Authors and Affiliations

  1. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA research center, 1200, Vienna, Austria

    Andrey V. Kozlov, Martijn van Griensven, Susanne Haindl, Ingeborg Kehrer, Mohammad Jafarmadar, Heinz Redl & Soheyl Bahrami

  2. Department for Biomedical Sciences, Veterinary University Vienna, 1210, Vienna, Austria

    J. Catharina Duvigneau, Romana T. Hartl & Thomas Ebel

  3. Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, 89070, Ulm, Germany

    Enrico Calzia & Peter Radermacher

  4. Daniel Swarovski Research Laboratory, Department of General and Transplant Surgery, Medical University Innsbruck, Innsbruck, Austria

    Erich Gnaiger

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  1. Andrey V. Kozlov
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Kozlov, A.V., van Griensven, M., Haindl, S. et al. Peritoneal Inflammation in Pigs is Associated with Early Mitochondrial Dysfunction in Liver and Kidney. Inflammation 33, 295–305 (2010). https://doi.org/10.1007/s10753-010-9185-4

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