High-Content Analysis/Screening for Predictive Toxicology: Application to Hepatotoxicity and Genotoxicity
| Autor: | Mikael Persson, Natacha S. Mow, Jorrit J. Hornberg, Anni F. Løye, Tomas Mow, Annemette V. Thougaard, Mélanie Jacquet |
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| Rok vydání: | 2014 |
| Předmět: |
Cost-Benefit Analysis
Pharmacology Biology Toxicology Bioinformatics medicine.disease_cause Bile Acids and Salts Toxicity Tests medicine Animals Humans Adverse effect Pharmaceutical industry Cholestasis business.industry Drug discovery food and beverages General Medicine Liver Drug development High-content screening Toxicity Micronucleus test Hepatocytes Chemical and Drug Induced Liver Injury business Genotoxicity DNA Damage |
| Zdroj: | Basic & Clinical Pharmacology & Toxicology. 115:18-23 |
| ISSN: | 1742-7835 |
| DOI: | 10.1111/bcpt.12200 |
| Popis: | High-content imaging/analysis has emerged as a powerful tool for predictive toxicology as it can be used for identifying and mitigating potential safety risks during drug discovery. By careful selection of end-points, some cellular assays can show better predictivity than routine animal toxicity testing for certain adverse events. Here, we present the perhaps most utilized high-content screening assays for predictive toxicology in the pharmaceutical industry. Multi-parametric imaging of cell health in simple and cost-effective model systems can be used to predict human hepatotoxicity and elucidate mechanisms of toxicity, and imaging of bile salt transport inhibition in sandwich-cultured hepatocytes can be used to predict cholestasis-inducing compounds. Imaging of micronuclei formation in simple cell models can be used to detect genotoxic potential and elucidate anuegenic or clastogenic mode of actions. The hope is that application of these relatively predictive assays during drug discovery will reduce toxicity and safety-related attrition of drug development programmes at later stages. |
| Databáze: | OpenAIRE |
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