P-066

Embryonic Zebrafish (Danio rerio) as part of an integrated strategy for nephrotoxicity testing

Prof. Dr. Angela Mally & Dr. Daniel Liedtke,
Universität Würzburg,

06/2018-05/2021

Embryonic zebrafish (Danio rerio) may help to overcome limitations of in vitro toxicity tests and close the gap between cell-based high-throughput assays and toxicity tests in animals.

The kidney is a major target organ of toxicity. Numerous structurally diverse drugs, natural compounds and chemicals can cause kidney injury. Presently, nephrotoxic effects of drugs and chemicals are identified primarily through regulatory toxicity tests in animals. With the aim of more efficient safety assessment and reduction of animal testing, toxicology is currently undergoing a paradigm shift in the way toxicity testing and risk assessment is carried out - away from tests in animals towards mechanism-based in vitro methods. While cell-based in vitro assays are particularly attractive for high-throughput screening, they fail to adequately reflect the complex processes that occur in vivo and thus do not allow prediction of potential health risks of drugs and chemicals with high confidence. Embryonic zebrafish (Danio rerio), which according to animal welfare legislation are considered as an in vitro model, are recognized as an alternative model for toxicity screening as they are easily accessible, releatively cheap and suitable for high-throuput methods, and - more importantly - better reflect the physiological situation of an intact organism (e.g. with respect to toxicokinetics, biotransformation) than cell-based in vitro assays.

Fig. 1:   Overview of the different methodological approaches used to assess nephrotoxicity in larval zebrafish exposed to model nephrotoxins.

Institution

Group Prof. Dr. Angela Mally:
Institut für Pharmakologie und Toxikologie
Universität Würzburg
Versbacher Straße 9, 97078 Würzburg

Dr. Daniel Liedtke:
Institut für Humangenetik
Biozentrum
Universität Würzburg
97074 Würzburg

Duration

06/2018 - 02/2021