Tuesday, 03 September 2013 12:28

ABCB4 transporter protects fish embryo from toxic substances: integrated test system recommended Featured

Researchers at the Helmholtz Centre for Environmental Research (UFZ) and colleagues from the Swiss aquatic research institute Eawag have discovered a protein that protects the zebrafish embryo by transporting toxic chemicals out of its body.

In their current press release, the ecotoxicologists Dr. Till Luckenbach (UFZ) and Dr. Stephan Fischer (Eawag) describe how the transport protein ABCB4 actively channels toxic chemicals out of the embryo of the zebrafish (Danio rerio), thus protecting it against toxic substances in the water.

This could be significant for ecotoxicological risk assessment. Just this July, the OECD approved an in vitro test for acute toxicity testing on zebrafish embryos (FET, OECD Guideline 236). The use of fish embryos is considered to be an in vitro test and thus an alternative to animal testing, because only the free-swimming larval stage of the fish is considered to be an animal. The new test allows the calculation of LC50, i.e. the lethal concentration of a variety of substances.

However, this protective mechanism of the embryos can be deactivated by certain other environmental chemicals, making the animals much more sensitive to toxic substances.

The researchers were able to demonstrate that the uptake of a few substances and the sensitivity to those substances actually increases when the ABCB4 transporter is deactivated.

However, there is no known case in which the effect of a chemical was underestimated because the interaction with the transporter system in the fish embryo was not taken into account is not known, according to Dr. Luckenbach from the UFZ. He recommends that first be determined whether chemicals interact with the ABCB4 transporter. The in vitro system with recombinant ABCB4 protein could be used to this end, as was done in the study.

The researchers advocate the implementation of an integrated test approach, in which specific in vitro systems (such as the recombinant protein) are used to detect the specific biological activity of substances.

The scientists have published their study in the journal “BMC Biology”.

Original publication:
Stephan Fischer, Nils Klüver, Kathleen Burkhardt Medicke, Mirko Pietsch, Anne-Marie Schmidt, Peggy Wellner, Kristin Schirmer & Till Luckenbach (2013 ) : ABCB4 acts as xenobiotic transporter and active barrier against chemical uptake in zebrafish (Danio rerio) embryos. BMC Biology 11:69. doi: 10.1186/1741-7007-11-69, www.biomedcentral.com/1741-7007/11/69

(in German) http://www.ufz.de/index.php?de=31974