Mitochondria are essential sub cellular organelles. Often referred to as the powerhouses of the cell, mitochondria are responsible for generating ATP which is the primary energy source of cells. Different tissue types contain different numbers of mitochondria ranging from one to several thousand.
Mitochondrial toxicity is often implicated in numerous drug-induced adverse events, including hepatic failure and cardiotoxicity. Using cell-based assays, Cyprotex has focused its efforts on identifying the likelihood of this occurring before a drug reaches the clinic. Our recent new research has involved comparing standard approaches for assessing mitochondrial toxicity (i.e., the Glu/Gal assay) with more in-depth analysis of mitochondrial function using the Seahorse XFe96 Flux Analyser.
Cyprotex’s UK Head of Toxicology, Dr. Paul Walker, presented the research at SOT in San Diego on the 26th March 2015. Titled ‘Improved Detection of Mitochondrial Toxicants Using Oxygen Consumption and Extracellular Acidification Rate in Comparison to the Glu/Gal Assay’, the poster evaluated a set of 72 non-mitochondrial and mitochondrial toxicants (drugs and chemicals) through both the Glu/Gal assay and the Seahorse assay.
The findings from the research indicate that a combined approach incorporating the Glu/Gal assay and the Seahorse assay as well as a Cmax value was the most predictive, giving a 91.5% accuracy, 81.5% sensitivity and 100% specificity. The Seahorse proved to be the most sensitive technique with correct identification of 78% of the mitochondrial toxicants (nearly double which were identified by the Glu/Gal assay). Furthermore, the Seahorse assay had the advantage of correctly identifying the mechanism of mitochondrial toxicity in over 70% of cases.
The poster can be downloaded from our website http://www.cyprotex.com/posters