Clinical signs of drug induced mitochondrial impairment range from obvious and severe to more subtle reflections of modest loss of mitochondrial capacity such as exercise intolerance, malaise, and mild lactic acidosis.
1Dykens JA and Will Y (2007) Drug Discovery Today 12; 777-785
|Media Assessed||Supplemented DMEM containing 25 mM glucose
Supplemented DMEM containing 10 mM galactose
|Cell Types Available||HepG2, U-87 MG, other custom cell lines|
|Test Article Concentration||0.03, 0.1, 0.3, 1, 3, 10, 30 and 100 µM (different concentrations available)|
|Final DMSO Concentration||0.5%|
|Number of Replicates||3 replicates per concentration|
|Analysis Method||MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide], determined by absorbance|
|Data Delivery||IC50 determination in the presence of glucose and galactose media
Minimum effective concentration (MEC) determination in the presence of glucose and galactose media
Fold change in Glu/Gal IC50
Cyprotex's mitochondrial toxicity service is a cell based assay which has been validated using a number of different mitochondrial toxicants and non-mitochondrial toxicant compounds.
A mitochondrial toxicant is indicated by a greater than three-fold change in IC50 value observed in the galactose media compared to the glucose media. Figure 1 illustrates the data for the mitochondrial toxicant, papaverine (A), and the non mitochondrial toxicant, tamoxifen (B). A 7.91 fold increase in IC50 value is observed for papaverine in galactose media compared with glucose media (table 1). No fold change was observed with the non-mitochondrial toxicant (tamoxifen).
|IC50 (µM)||Fold Change in IC50|
1 Dykens JA and Will Y (2007) Drug Discovery Today 12; 777-785
2 Marroquin LD et al., (2007) Toxicol Sci (97)2; 539-547