Mitochondria in chemical-induced toxicity

Stel, W. van der (2022)

Doctoral Thesis

Chemical-induced organ toxicity is a major concern in the development and use of chemicals, including drugs, pesticides, industrial chemicals and cosmetics. In the last decades, the onset and progression of chemical-induced organ toxicity has been linked amongst others to perturbation of mitochondria.
In this work, we set out to further unravel the mechanisms behind mitochondrial toxicity initiated by a chemical insult. More in-depth and biology driven assessment of the onset and progression of mitochondrial perturbation supports the development of relevant prediction tools. We aimed to stimulate the integration of these in vitro and in silico prediction tools in the safety assessment of existing and new chemicals, to allow detailed assessment of mitochondrial fitness upon chemical exposure.

• Mitochondria
• ETC complex inhibition
• TempO-seq
• High content imaging
• Adverse outcome pathway
• Toxicity prediction
• In vitro test models

• All authors: Stel, W. van der
• Supervisor: Danen, E.H.J.; Water, B. van de
• Committee: Irth, H.; Bouwstra, J.A.; Russel, F.G.; Kamp, H.; Hankemeier, T.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
• Date: 2022-02-01
• ISBN (print): 9789464215731