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BioMed Research International
Volume 2015, Article ID 353074, 12 pages
Research Article

Dose Response of Endotoxin on Hepatocyte and Muscle Mitochondrial Respiration In Vitro

1Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, Freiburgstraße 10, 3010 Bern, Switzerland
2Graduate School for Cellular and Biomedical Sciences, University of Bern, Switzerland
3Department of Anesthesiology and Pain Therapy, Inselspital, Bern University Hospital and University of Bern, 3010 Bern, Switzerland

Received 5 June 2014; Revised 22 August 2014; Accepted 8 September 2014

Academic Editor: Marko Ljubkovic

Copyright © 2015 Victor Jeger et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction. 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). Conclusion. 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.