Related Experiment Video
Updated: Apr 5, 2026
A Strategy to Identify Compounds that Affect Cell Growth and Survival in Cultured Mammalian Cells at Low-to-Moderate Throughput
Published on: September 22, 2019
A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro
Melanie Adler1, Susanne Ramm2, Marc Hafner2
1Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, Massachusetts; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts;
A new high-throughput method uses heme oxygenase-1 (HO-1) as a biomarker to predict drug and chemical nephrotoxicity. This approach with human proximal tubular epithelial cells (HPTECs) offers faster, more accurate kidney toxicity assessments for safer therapeutics.
Area of Science:
- Toxicology
- Biomarker Discovery
- In Vitro Toxicology
Background:
- Nephrotoxicity from drugs and chemicals causes significant health issues.
- Current methods lack high-throughput capabilities for predictive assessment.
- Primary human proximal tubular epithelial cells (HPTECs) are suitable for in vitro toxicity testing.
Purpose of the Study:
- To identify a reliable biomarker for predicting nephrotoxicity.
- To develop a high-throughput in vitro assay for assessing kidney toxicity.
Main Methods:
- Multiplexed gene expression profiling of HPTECs exposed to nephrotoxicants.
- Investigated heme oxygenase-1 (HO-1) as a potential biomarker.
- Validated HO-1 translatability across species and platforms (rat toxicogenomic databases, kidney-on-a-chip).
- Tested HO-1 predictive performance using a panel of 39 nephrotoxic compounds.
- Developed a homogenous time-resolved fluorescence assay for high-throughput screening.
Main Results:
- HO-1 overexpression correlated with increasing doses of six nephrotoxicants.
- HO-1 protein deregulation was confirmed for all nine tested nephrotoxicants.
- HO-1 demonstrated strong predictive potential (AUC-ROC=0.89), outperforming traditional viability assays.
- Combining HO-1 with cell count further improved predictive accuracy (AUC-ROC=0.92).
Conclusions:
- HO-1 is a sensitive and predictive biomarker for nephrotoxicity.
- A novel high-throughput cell-based assay using HO-1 enables rapid screening of potential nephrotoxic agents.
- This approach can accelerate the assessment of therapeutic and environmental chemical safety.
