Effect of nephrotoxicants and hepatotoxicants on gene expression profile in human peripheral blood mononuclear cells

Area of Science:

• Toxicogenomics
• Molecular Toxicology
• Biomarker Discovery

Background:

• Peripheral blood transcriptome analysis is a promising area in toxicogenomics for identifying translational toxicity markers.
• Xenobiotics causing toxicity via similar mechanisms often produce distinct gene expression patterns.
• Accessible surrogate tissues like blood are valuable for studying drug-induced perturbations.

Purpose of the Study:

• To assess the transcriptomic response of human peripheral blood mononuclear cells (hPBMC) to drug-induced toxicity.
• To derive gene expression patterns indicative of specific organ (kidney or liver) injury.
• To identify a gene signature for differentiating drug-induced kidney versus liver toxicity.

Main Methods:

• Exposure of hPBMC to conventional drugs known to cause kidney or liver injury.
• Classification of drugs into kidney-affecting and liver-affecting groups.
• Gene expression analysis and hierarchical clustering to identify distinct patterns.

Main Results:

• Drug exposure altered the transcriptional profile of hPBMC.
• A set of 365 genes was identified that can discriminate between kidney- and liver-targeting drugs.
• Unique gene expression patterns indicative of specific organ toxicity were deduced.

Conclusions:

• Transcriptional profiling of hPBMC can reflect drug-induced organ toxicity.
• The identified gene signature patterns hold potential for qualifying and identifying drug-induced toxicity.
• This approach may advance the development of predictive biomarkers for drug safety.