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Nephrotoxicity: Topical issue.

Alena Gabelova1, Katarina Kozics1, Lucyna Kapka-Skrzypczak2

  • 1Cancer Research Institute, Biomedical Research Center SAS, Dubravska cesta 9, 845 05 Bratislava, Slovakia.

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
|September 29, 2019
PubMed
Summary

Developing reliable in vitro kidney models is crucial for predicting drug-induced kidney injury and reducing pharmaceutical development failures. The single cell gel electrophoresis (SCGE) comet assay shows promise but requires standardized methods for effective nephrotoxicity screening.

Keywords:
Comet assayHuman renal cellsIn vitro kidney modelsNephrotoxicityRisk assessment

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Area of Science:

  • Toxicology
  • Pharmacology
  • Biotechnology

Background:

  • Drug-induced kidney injury is a major challenge in chemotherapy and drug development.
  • Environmental xenobiotics also pose risks to kidney health.
  • Current in vitro kidney models and assays inadequately predict nephrotoxicity.

Purpose of the Study:

  • To review human cell lines used as in vitro kidney models for nephrotoxicity studies.
  • To evaluate the potential of the single cell gel electrophoresis (SCGE) comet assay for screening kidney toxicants.
  • To highlight the need for standardized methods and validation for predictive nephrotoxicity testing.

Main Methods:

  • Overview of existing human cell lines for in vitro kidney modeling.
  • Discussion of the single cell gel electrophoresis (SCGE)/comet assay's application in nephrotoxicity.
  • Analysis of methodological variability in SCGE assays.

Main Results:

  • Various human cell lines serve as surrogates for in vitro kidney models, each with limitations.
  • The SCGE comet assay has potential for detecting drug-induced kidney damage.
  • Significant variability exists in current SCGE methodologies.

Conclusions:

  • There is an urgent need for improved in vitro human kidney models and predictive assays.
  • Standardized guidelines and inter-laboratory validation are essential before adopting the SCGE comet assay for routine nephrotoxicity testing.
  • Further research is required to establish the feasibility and robustness of the comet assay for early-stage drug discovery and xenobiotic screening.