AIMMS researcher Dr. Shalenie den Braver-Sewradj has won the Joep van den Bercken award

The Joep van den Bercken prize is awarded for the best PhD-thesis in Toxicology

07/15/2019 | 12:06 PM

At the Annual Meeting of the Dutch Society of Toxicology, in June 2019, Prof. dr. Henk van Loveren, president of the Dutch Society of Toxicology (NVT), awarded the Joep van de Bercken prize to Dr. Shalenie den Braver-Sewradj for the best PhD-thesis in Toxicology defended in 2018. The competitive award has been established as a tribute to Prof. dr. Joep van den Bercken, a neurtoxicologist from UTOX, is aiming to stimulate young Dutch toxicologists and consists of an invited lecture, a plaque and € 1000. Based on the Jury’s report, Prof. Van Loveren highlighted the innovative aspects of Den Braver-Sewradj’s research as well as the exceptional contributions to the field of Toxicology and Drug safety.

The PhD-thesis of Den Braver-Sewradj, entitled ‘Inter-individual variation in hepatic drug metabolism - the potential of in vitro assays in unraveling the role of metabolism in drug induced liver toxicity’, was nominated by Prof. Nico Vermeulen, dr. Jan Commandeur and dr. Chris Vos, the supervisory team from AIMMS-Molecular Toxicology at VU Amsterdam. The research described in the thesis was aimed to a) assess the impact of primary human hepatocyte culture conditions on the drug metabolizing enzyme activity and/or donor variability, and b) to investigate variability of up to 26 individual drug metabolizing (iso-)enzyme activities as a risk factor for serious adverse drug reactions (ADRs), due to increased exposure to chemically reactive metabolites from hepatotoxic drugs, like Diclofenac, Clozapine and Paracetamol. For this purpose, livers from 20 human donors were used. The thesis elucidated a significant impact of specific cell culture conditions on Sulfo-transferase enzyme activities and on donor variability. Cytochrome P450 and Glucuronosyl-transferase enzyme activities were also dependent on culture conditions, however, donor variability was well preserved. In addition, the results showed a high inter-individual variability in the iso-enzyme’s capacity to form chemically reactive drug metabolites as well as in their capacity to detoxify them. Overall, the results not only contribute significantly to a better understanding of inter-individual variability and susceptibility to Drug-induced Liver Injury (DILI) in humans, but they also provide a novel and unique data set for in vitro-in vivo modeling of the disposition, pharmacokinetics and safety of drugs causing serious liver toxicity.

The PhD-thesis of Shalenie Den Braver-Sewradj can be found here.