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Tools to Measure Cell Health and Cytotoxicity Using High Content Imaging and Analysis.

Bhaskar S Mandavilli1, Robert J Aggeler2, Kevin M Chambers2

  • 1Thermo Fisher Scientific, 29851 Willow Creek Road, Eugene, OR, 97402, USA. Bhaskar.mandavilli@thermofisher.com.

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Summary
This summary is machine-generated.

High content screening (HCS) offers multiparametric measurements for early toxicity testing and safety assessment. This method evaluates drug-induced liver injury by measuring mitochondrial dysfunction, oxidative stress, and lipid metabolism defects.

Keywords:
CytotoxicityMitochondrial membrane potentialOxidative stressPlasma membrane integrityReactive oxygen species

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Area of Science:

  • Biochemistry
  • Toxicology
  • Drug Development

Background:

  • High content screening (HCS) enables multiparametric measurements crucial for early toxicity testing and safety assessment in drug development.
  • Evaluating the impact of food supplements and environmental toxicants also benefits from HCS-based assessments.
  • Key markers for drug-induced liver injury include mitochondrial membrane potential, plasma membrane permeability, oxidative stress, phospholipidosis, and steatosis.

Purpose of the Study:

  • To describe fluorescent reagents and protocols for measuring key toxicity parameters using HCS.
  • To detail methodologies for assessing mitochondrial dysfunction, oxidative stress, and lipid accumulation in hepatotoxicity investigations.
  • To provide a framework for evaluating drug or chemical compound-induced liver injury.

Main Methods:

  • Utilizing high content imaging-based methodologies and instrumentation.
  • Employing fluorescent reagents for multiparametric measurements.
  • Focusing on assays for mitochondrial membrane potential, plasma membrane permeability, oxidative stress, phospholipidosis, and steatosis.

Main Results:

  • Established protocols for HCS-based measurement of critical toxicity markers.
  • Demonstrated the utility of HCS in assessing drug-induced liver injury.
  • Provided insights into the relationship between mitochondrial dysfunction, oxidative stress, and lipid metabolism defects.

Conclusions:

  • HCS is a powerful tool for comprehensive toxicity testing and safety assessment.
  • The described methods facilitate the routine study of drug-induced phospholipidosis and steatosis.
  • Accurate measurement of these parameters aids in determining the risks and fate of chemical compounds.