Toxicogenomic-based approaches predicting liver toxicity in vitro

Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury

“…Another type of high content readout involves toxicogenomics (TGx), which combines genomics (i.e., mRNA transcripts, microRNAs, DNA methylation patterns, and single nucleotide polymorphisms) and bioinformatics analyses to characterize genes and pathways underlying drugs' effects on cells [ 96 ]. Changes at the gene expression level may precede cellular damage and could thus be useful to identify the mechanisms by which a drug may cause injury following prolonged exposure.…”

Highlight report: Blueprint for stem cell differentiation into liver cells

“…Furthermore, since cultivated liver cells are a basic tool for testing the effects of new medicinal drugs, hepatocyte-like cells can become an important alternative to animal testing (Ghallab et al, 2013[ 5 ], 2014[ 4 ][ 6 ]). Currently such alternative in vitro systems play a major role in testing of neurotoxicity (Waldmann et al, 2014[ 20 ]; Zimmer et al, 2014[ 23 ]; Krug et al, 2013[ 17 ]), nephrotoxicity (Faiz et al, 2015[ 3 ]; Yang et al, 2014[ 21 ]) and hepatotoxicity (Heise et al, 2012[ 13 ]; Godoy et al, 2009[ 9 ]; Godoy 2011[ 7 ]; Godoy and Bolt, 2012[ 8 ]; Grinberg et al, 2014[ 12 ]; Hengstler et al, 2000[ 15 ]). The results are also important, because medicinal and toxic substances are currently being tested with hepatocyte-like cells, and now it becomes possible to determine how trustworthy the results can be.…”

Systems Toxicology

“…Understanding the mechanisms of organ toxicity has always been a major goal in toxicology (Campos et al, 2014[ 3 ]; Hammad, 2014[ 17 ]; Godoy et al, 2015[ 16 ], 2013[ 15 ], 2012[ 13 ], 2009[ 14 ]; Dias da Silva et al, 2013[ 4 ]; Driessen et al, 2013[ 9 ]; Shimada et al, 2012[ 26 ]; Baulies et al, 2015[ 2 ]; Reif, 2014[ 23 ][ 24 ]). In many circumstances Systems Toxicology techniques may help to gain a deeper understanding, particularly in situations where several mechanisms interact and due to high complexity the situation is difficult to understand intuitively (Widera et al, 2014[ 30 ]; Friebel et al, 2015[ 10 ]; Bartl et al, 2015[ 1 ]).…”