Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data.

International Journal of Molecular Sciences
Patric SchymanAnders Wallqvist

Abstract

The immense resources required and the ethical concerns for animal-based toxicological studies have driven the development of in vitro and in silico approaches. Recently, we validated our approach in which the expression of a set of genes is uniquely associated with an organ-injury phenotype (injury module), by using thioacetamide, a known liver toxicant. Here, we sought to explore whether RNA-seq data obtained from human cells (in vitro) treated with thioacetamide-S-oxide (a toxic intermediate metabolite) would correlate across species with the injury responses found in rat cells (in vitro) after exposure to this metabolite as well as in rats exposed to thioacetamide (in vivo). We treated two human cell types with thioacetamide-S-oxide (primary hepatocytes with 0 (vehicle), 0.125 (low dose), or 0.25 (high dose) mM, and renal tubular epithelial cells with 0 (vehicle), 0.25 (low dose), or 1.00 (high dose) mM) and collected RNA-seq data 9 or 24 h after treatment. We found that the liver-injury modules significantly altered in human hepatocytes 24 h after high-dose treatment involved cellular infiltration and bile duct proliferation, which are linked to fibrosis. For high-dose treatments, our modular approach predicted the rat in ...Continue Reading

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Citations

Feb 27, 2021·Frontiers in Pharmacology·Patric SchymanAnders Wallqvist

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Datasets Mentioned

BETA
GSE134641

Methods Mentioned

BETA
RNA-seq
PCA
Assay

Software Mentioned

Ensemble
Sleuth
Kallisto
David Gene Functional Classification Tool

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