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Early septic shock induces loss of oxidative phosphorylation yield plasticity in liver mitochondria

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Abstract

We aimed to study the change in mitochondrial oxidative phosphorylation efficiency occurring at the early stage of septic shock in an experimental model. Thirty-six male Wistar rats were divided into two groups. In the first group, a cecal ligation and puncture (CLP) was carried out to induce septic shock for 5 h. The second group includes sham-operated rats and constitutes the control group. Blood gas analysis, alanine amino transferase, and lactic acid dosages were assayed 5 h after surgery. Liver mitochondria were isolated for in vitro functional characterization, including mitochondrial respiratory parameters, oxidative phosphorylation efficiency, oxi-radical production, membrane potential, and cytochrome c oxidase activity and content. Liver interleukin 1β (IL-1β) and tumor necrosis α mRNA levels were determined. Septic shock induced a severe hypotension occurring 180 min after CLP in association with a metabolic acidosis, an increase in plasma alanine amino transferase, liver IL-1β gene expression, and mitochondrial reactive oxygen species production. The rates of mitochondrial oxygen consumption and the activity and content of cytochrome c oxidase were significantly decreased while no alterations in the oxidative phosphorylation efficiency and inner membrane integrity were found. These results show that contrary to what was expected, liver mitochondria felt to adjust their oxidative phosphorylation efficiency in response to the decrease in the mitochondrial oxidative activity induced by CLP. This loss of mitochondrial bioenergetics plasticity might be related to mitochondrial oxidative stress and liver cytokines production.

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Acknowledgment

This study was funded by Equipe d'Accueil EA 4174, Université Claude Bernard Lyon 1.

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Authors and Affiliations

  1. Laboratoire Hémostase, Inflammation, et Sepsis; EA 4174, Université Claude Bernard Lyon 1, 69008, Lyon, France

    Pierre Eyenga, Jérôme Morel, Claude Négrier & Jean Paul Viale

  2. Laboratoire d’Ecologie des Hydrosystèmes Naturels et Anthropisés; UMR 5023; CNRS, Université Claude Bernard Lyon 1, 69622, Villeurbanne, France

    Damien Roussel, Caroline Romestaing & Loic Teulier

  3. Inserm U 870; INRA 1235, Université Claude Bernard Lyon 1, 69008, Lyon, France

    Joelle Goudable

  4. Department of Translational Medicine, Thomas Jefferson University, 19107, Philadelphia, PA, USA

    Shey-Shing Sheu

  5. Laboratoire de Biométrie et Biologie Evolutive; UMR 5558; CNRS, Université Claude Bernard Lyon1, 69622, Villeurbanne, France

    Benjamin Rey

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  1. Pierre Eyenga
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Correspondence to Jean Paul Viale.

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Eyenga, P., Roussel, D., Morel, J. et al. Early septic shock induces loss of oxidative phosphorylation yield plasticity in liver mitochondria. J Physiol Biochem 70, 285–296 (2014). https://doi.org/10.1007/s13105-013-0280-5

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