Articles
High-Content Imaging Analysis Of Cell Loss, Cellular Redox State, ROS Production And Mitochondrial Membrane Potential Predict Drug Hepatotoxicity
July 8, 2010
•Poster: High-Content Imaging Analysis Of Cell Loss, Cellular Redox State, ROS Production And Mitochondrial Membrane Potential Predict Drug Hepatotoxicity
By Life Science Research - Cellomics
Cellular redox homeostasis is critical for maintaining normal cell physiology against damage induced by oxidative stress. Cellular redox processes are involved in many cell-signaling events that can lead to cytoprotection, differentiation, cell proliferation and cell death. Reactive oxygen species (ROS) are primarily generated through normal metabolic processes but it is also produced by toxic insults to cells. Once ROS production exceeds the cell's antioxidant capacity, it can directly damage components that maintain cell physiology, such as cellular proteins, lipids and DNA or by affecting the signaling pathways. Because of the danger posed by ROS and cellular oxidation in cells and tissues, measuring ROS production and cellular redox status in combination with other cytotoxicity markers is used to predict the hepatotoxicity of different compounds. We thus developed a quantitative and multiplexed cell-based high-content imaging assay to monitor cell loss, cellular redox status with glutathione levels, ROS generation and mitochondrial membrane potential changes using specific fluorescent probes. Hepatic cell models treated with a panel of control compounds and compounds known to induce liver injury were labeled with the fluorescent probes, automatically imaged, and analyzed by individual assay targets or by multiplexing all the targets. ROC (receiver-operating characteristic) curve analysis and Boolean logic showed that multiplexed targets give better prediction on drug hepatotoxicity with high specificity and high sensitivity. Thus, with high-content imaging analysis, we were able to perform fast and accurate hepatotoxicity detection of drugs in both live and fixed cells on high density microplates.
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