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Evaluation of mitochondrial respiration in cultured rat hepatocytes.

Jean-Pierre JP Marchandeau and Gilles G Labbe

Methods Mol Biol (2011) PMID 20972757

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 pre-incubated with drug.

DOI: 10.1007/978-1-60761-849-2_14
Version: za2963e q8za5 q8zb3 q8zcf q8zd8 q8zef q8zf3 q8zg5

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