Nephrotoxicity: topical issue

Publication date: Available online 6 December 2018Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Alena Gabelova, Katarina Kozics, Lucyna Kapka-Skrzypczak, Marcin Kruszewski, Monika SramkovaAbstractDrug-induced kidney injury is one of the most significant adverse events and dose limiting factor in chemotherapy as well a major cause of prospective drug attrition during pharmaceutical development. Moreover, kidney injury can also occur as a consequence of exposures to environmental xenobiotics such as heavy metals, fungal toxins and nanomaterials. The lack of adequate in vitro human kidney models that mimic more realistically the in vivo conditions and the absence of suitable and robust, cost-effective and predictive cell-based in vitro assays contribute to an underestimation of the kidney toxic potential of new drugs and xenobiotics. Therefore, a rapid screening system capable to detect potential nephrotoxicity at early stages of drug discovery is an urgent need. Here we provide an overview of human cell lines currently used as a surrogate in vitro kidney models in nephrotoxicity studies, including their advantages and limitations. In addition, the capacity of the single cell gel electrophoresis (SCGE)/comet assay as a potential tool in kidney toxicants screening is discussed. Despite a limited number of studies using the comet assay to evaluate the drug-induced kidney damage potential, a considerable variability in SCGE methodology (e.g. l...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research