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Gene networks-based mechanistic assessment of drug-induced organ toxicity: a focus on liver and kidney

Drug induced organ toxicity is the main problem of the drug development and drug usage in the clinic. The liver and kidneys are the most sensitive organs towards drug induced toxicity.

Wijaya, L.S.
15 december 2022
Thesis in Leiden Repository

The liver neutralizes xenobiotic to which human are exposed to while the kidneys remove waste products from the blood. Due to their detoxification function, these organs are continuously exposed to high amount of toxicants leading to potential injury. Investigating the molecular and cellular mechanisms contributing to drug-induced liver injury (DILI) and drug-induced kidney injury (DIKI) will open new avenues that can help in the prediction of induced organ injury caused by drugs as well as other xenobiotics.In this thesis, we mapped the dynamics of cellular stress responses in the liver and kidneys upon the exposure of a set of model compounds in order to gain a more holistic insight in DILI and DIKI. We conducted multiple extensive in vitro and in vivo studies to understand the dynamics of these cellular responses and determined the translation of our findings from in vitro to in vivo. Transcriptomics analysis was central in the research which was complemented with other methodologies, such as reporter cell assay, immunohistochemistry, to unravel the mechanisms of drug-induced organ toxicity in both liver and kidney. 

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