Gene expression data from primary human hepatocytes treated with tolvaptan for 4, 24, or 72 h

A micropatterned coculture model (HepatoPac®) was used to explore the possibility that changes in exosome content precede overt necrosis in response to tolvaptan, a drug known to cause idiosyncratic drug-induced liver injury. Hepatocytes from 3 human donors were exposed to a range of tolvaptan concentrations bracketing plasma Cmax (0.01 - 50 µM) or DMSO control continuously for 4, 24, or 72 h. While ALT release was not significantly affected, tolvaptan exposure resulted in increased release of exosomal microRNA-122 (miR-122) into the medium. Microarray analysis was used to idenfity the activation of molecular stress response pathways most associated with increases in exosomal miR-122. 54 samples were analyzed representing N=1 per donor, time point, treatment, and concentration