Assessing Hepatoxicants based on High-throughput Quantitativ | 50220
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International Research Journal of Biotechnology

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Assessing Hepatoxicants based on High-throughput Quantitative SILAC Proteomics and Causal Biological Networks


Ahmed Enayetallah

termination of compounds in preclinical development, as well as withdrawal of marketed drugs. Identification of the signaling pathways and proteins involved in injury is an important step towards establishing assays that could be utilized to identify potential hepatotoxicants early in the drug discovery process. In this study we used high throughput quantitative mass spectrometry proteomics involving Stable Isotope Labeling with Amino acids in Cell culture (SILAC) leveraged by a recently developed systems biology approach (Causal Reasoning Engine, CRE) to investigate the effects of hepatotoxic compounds on the cellular proteome of HepG2 cells. Cells were treated with various concentrations of nefazadone, nimesulide, nomifensine, or glafenine, all of which cause hepatotoxicity in humans. Buspirone and rosiglitazone were used as comparator compounds not associated with hepatotoxicity

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