Friday, 25 October 2019 13:04

Animal Welfare Research Award of the Federal Ministry of Food and Agriculture goes to young IfADo researcher Featured

This year's 38th Animal Welfare Research Award of the Federal Ministry of Food and Agriculture was given to Wiebke Albrecht from the Leibniz Institute for Work Research at the Technical University of Dortmund (IfADo). Together with international colleagues, she has developed a method to evaluate and improve the performance of in vitro liver toxicity test systems.


Ms. Albrecht has not only convinced but also inspired the jury with her work, said the State Secretary Dr. Hermann Onko Aeikens and stressed the practical relevance of her work. The minister of agriculture, Julia Klöckner, emphasized that animal experiments had to be based on the absolutely essential would have to be kept to a minimum; in the best case, they could be completely eliminated and replaced by modern methods. To this end, this year's prizewinner Wiebke Albrecht makes an important contribution.

 



Minister of Agriculture, Julia Klöckner, and prizewinner, Wiebke Abrecht.
Photo: Christiane Hohensee


A possible risk of liver damage for humans caused by substances such as drugs cannot be reliably detected in animal experiments. However,  alternatives in the form of modern test systems made of human liver cells are not able to determine exactly whether the substance is actually toxic or harmless in vivo in humans. It has also not yet been possible to reliably assess which of the huge number of measurements are best suited to assess the in vivo situation in the organism after the oral ingestion of a drug.

This is where the new method developed by prizewinner Wiebke Albrecht and her team comes in. She developed two mathematical formulas, which give indices for that questions. One can be used to assess the Yes/No situation, whether a substance is liver-toxic or not (the so-called toxicity separation index, TSI). The second index has been developed in order to accurately estimate at what concentration liver-toxic effects are likely to occur in the body (toxicity stimulation index, TEI). Following a complicated analysis process on the basis of the input data, the system displays an extrapolation plot, which is used to show the results. The model is applicable if the maximum blood concentration of the test substance in humans is known.

In order to test her model for the suitability, the scientist tested 28 drugs of known toxicity or non-toxicity in primary human hepatocytes and applied the new model then. In this approach, drugs were additionally tested, from what the concentration at which liver toxicity occurs is well-known. The results were promising: All liver-toxic drugs were correctly predicted with the model. Only in two cases of the non-toxic drugs, false-positive results were obtained. During the optimization process of the model, the team of scientists also discovered that the optimal cell incubation time for the tests is not several days, but only 24 hours. They also found out that it is more accurate to use the concentration as the lowest toxic concentration at which 10 percent of the cells have died.

The findings have direct practical relevance for use of in vitro cell cultures and the transferability of the results to the actual human situation in humans. The model also made it possible to reliably determine the maximum amounts of a food additive can be consumed safely every day (Margin of Safety). Thus complex feeding studies with animals can be avoided.

Original publication:
Albrecht, W., Kappenberg, F., Brecklinghaus, T. et al.: Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentration. Arch. Toxicol. 93: 1609-1637 (2019). doi: 10.1007/s00204-019-02492-9

Click here for the press release:
https://www.ifado.de/2019/10/22/tierschutzforschungspreis-2019-bmel/