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ABSTRACT: Drug-induced liver injury



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Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFα-mediated hepatotoxicity.

Fredriksson Lisa L   Wink Steven S   Herpers Bram B   Benedetti Giulia G   Hadi Mackenzie M   de Bont Hans H   Groothuis Geny G   Luijten Mirjam M   Danen Erik E   de Graauw Marjo M   Meerman John J   van de Water Bob B  

Toxicological sciences : an official journal of the Society of Toxicology 20140420 1

Drug-induced liver injury (DILI) is an important clinical problem. Here, we used a genomics approach to in detail investigate the hypothesis that critical drug-induced toxicity pathways act in synergy with the pro-inflammatory cytokine tumor necrosis factor α (TNFα) to cause cell death of liver HepG2 cells. Transcriptomics of the cell injury stress response pathways initiated by two hepatoxicants, diclofenac and carbamazepine, revealed the endoplasmic reticulum (ER) stress/translational initiati  ...[more]

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