Mitochondria are a common target for drug-induced liver injury, but mitochondrial dysfunction also plays a crucial role in several other pathologies such as neurodegenerative diseases and accelerated aging. The ability to analyse and assess such mitochondrial dysfunction is challenging in that investigational conclusions can be dependent on the cell type and assay being used.
Cyprotex are members of the EU-ToxRisk consortium, which is funded by the European Union’s Horizon 2020 Research and Innovation programme. Through this project, Cyprotex have co-authored a recent publication in Archives of Toxicology entitled: ‘Multiparametric assessment of mitochondrial respiratory inhibition in HepG2 and RPTEC/TERT1 cells using a panel of mitochondrial targeting agrochemicals’.
The paper details a systematic approach to assessing the suitability of a range of different assay types with the view to formulating a consensus driven mitochondrial toxicity testing platform. Two different human cell types were selected, HepG2 and RPTEC/TERT1, and were exposed to a panel of 20 different agrochemicals chosen for their selective inhibition of the electron transport chain. A series of assays were performed such as lactate production, mitochondrial membrane potential and the simultaneous quantification of extracellular acidification and cellular oxygen consumption. In addition, the study utilised the mitochondrial respiratory complex assay developed at Cyprotex to determine complex inhibition specificity. The paper presents a comprehensive case for a mitochondrial assessment workflow, in particular with regards to establishing key measurable events of C1 and C3 electron transport chain inhibition, and represents a robust foundation on which to build future efforts.
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