Evaluation of Mitochondrial Respiration in Cultured Rat Hepatocytes

  • Jean-Pierre Marchandeau
  • Gilles LabbeEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1641)


Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects, such as lactic acidosis and rhabdomyolysis, in some patients. Several in vitro and in vivo investigations can be performed in order to determine if drugs can disturb mitochondrial fatty acid oxidation (FAO) and the oxidative phosphorylation (OXPHOS) process, deplete hepatic mitochondrial DNA (mtDNA), or trigger the opening of the mitochondrial permeability transition pore (MPT). Among these investigations, mitochondrial respiration is a relatively easy test to measure the potential toxicity of a drug. The use of cells instead of isolated mitochondria allows one to test the toxic effect of a parent compound and its metabolites. The use of rat hepatocytes can detect drugs involved in drug-induced liver injuries (DILI). The method consists in measuring oxygen consumption by using a Clark electrode in a chamber containing a suspension of hepatocytes preincubated with drug.

Key words

Mitochondrial respiration Oxygen consumption Clark electrode Respirometer Primary rat hepatocytes 



The authors would like to thank Delphine Hoët for her expertise and her support in hepatocyte culture.


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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Investigative Toxicology, Preclinical SafetySanofi R&DVitry-sur-SeineFrance

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