Mechanisms of Drug Induced Liver Injury: Toxicogenomics studies in differint in vitro models

Drug-induced liver injury (DILI) is a severe health condition that may result in morbidity and mortality. It adds financial burden on families and healthcare systems. It is not clear what happens, on the molecular level, during DILI. Through comparing genome-wide expression changes in different cell models associated with exposures to DILI-causing agents, we depict the molecular mechanisms of mitochondrial damage and alterations in ceramide metabolism during DILI development. Using a 3D co-cultured model, we also demonstrate the interactions between hepatocytes and Kupffer cells during the inflammation-associated increase in drug toxicity. Our findings would help the development of more sensitive biomarkers that provide early and sensitive detection/diagnosis of DILI.