Interference Effect of Sodium Valproate on Hepatocyte Biofunctional Networks Based on Bioinformatics Analysis

Abstract

Abstract: Objective To investigate the interference of sodium valproate (VPA) on hepatocyte bioprocessing/pathways by using published original data of rat hepatocyte-derived gene microarrays and to provide a basis for further studies on the mechanism of VPA toxicity. Methods Data of GSE40338 from VPA-treated rat primary hepatocytes in NCBI database was analyzed by GCBI online platform. The data was divided into control group and experimental group for differential gene analysis, Gene Ontology analysis and pathway analysis. Results Gene microarray analysis showed that different doses and incubation times of VPA treatment induced different gene regulations on hepatocytes. Further analyses suggest that VPA might interfer with the processes of biological processes, metabolism, development and etc. Pathways associated with development mainly include vasculogenesis, embryonic development, neurodevelopment and organ development. And the enrichments of organ development and neurodevelopment were much stronger than others. Conclusion Genomic analysis of hepatocytes in vitro indicates that in addition to metabolism, VPA can interfere with a variety of biological processes, including disruption of developmental bio-functional networks, implying that it is associated with organ developmental and neurodevelopmental toxicities. This study indicates that in-depth analysis of bio-networks/processes of gene microarray data is of important value in predicting toxicity of a drug and understanding its mechanism.

Key words: sodium valproate, primary hepatocytes, genomics, biological function, prediction of toxicity

CLC Number:

R992

WU Shou-yan, HUANG Gui-hua,, ZHAO Wen-jing , WANG Bing-shun, GONG Li-kun. Interference Effect of Sodium Valproate on Hepatocyte Biofunctional Networks Based on Bioinformatics Analysis[J]. Chinese Journal of Pharmacovigilance, 2017, 14(12): 705-710.

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