title: Dose response of endotoxin on hepatocyte and muscle mitochondrial respiration in vitro.
abstract: BACKGROUND
  Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria.
  
  
  METHODS
  Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1-100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry.
  
  
  RESULTS
  In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS).
  
  
  CONCLUSIONS
  LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner.
authors: Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, Freiburgstraße 10, 3010 Bern, Switzerland ; Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland.
authors: Victor
authors: 0000-0002-6785-3724
authors: V
authors: Jeger
authors: Department of Anesthesiology and Pain Therapy, Inselspital, Bern University Hospital and University of Bern, 3010 Bern, Switzerland.
authors: Sebastian
authors: S
authors: Brandt
authors: Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, Freiburgstraße 10, 3010 Bern, Switzerland.
authors: Francesca
authors: F
authors: Porta
authors: Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, Freiburgstraße 10, 3010 Bern, Switzerland.
authors: Stephan M
authors: SM
authors: Jakob
authors: Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, Freiburgstraße 10, 3010 Bern, Switzerland.
authors: Jukka
authors: J
authors: Takala
authors: Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, Freiburgstraße 10, 3010 Bern, Switzerland.
authors: Siamak
authors: S
authors: Djafarzadeh
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D034421:Sus scrofa; D013997:Time Factors
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate
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