Journal Article

TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

Gao, Shixiang, Wang, Zunyao, Du, Zhongkun, Zhang, Yan, Peng, Jianbiao, Wang, Guowei

2016

Overview

Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0.050 mg/L and 0.300 mg/L triphenyl phosphate for 7 days. Metabolomic analysis revealed significant changes in the contents of glucose, UDP-glucose, lactate, succinate, fumarate, choline, acetylcarnitine, and several fatty acids. Transcriptomic analysis revealed that related pathways, such as the glycosphingolipid biosynthesis, PPAR signaling pathway and fatty acid elongation, were significantly affected. These results suggest that triphenyl phosphate exposure markedly disturbs hepatic carbohydrate and lipid metabolism in zebrafish. Moreover, DNA replication, the cell cycle, and non-homologous end-joining and base excision repair were strongly affected, thus indicating that triphenyl phosphate hinders the DNA damage repair system in zebrafish liver cells. The present study provides a systematic analysis of the triphenyl phosphate-induced toxic effects in zebrafish liver and demonstrates that low concentrations of triphenyl phosphate affect normal metabolism and cell cycle.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 140/131 / 45/91 / 631/92/1643 / 64/116 / 704/172/169 / Animals / Base excision repair / Biosynthesis / Carbohydrate metabolism / Carbohydrate Metabolism - drug effects / Carbohydrate Metabolism - genetics / Cell cycle / Cell Cycle - drug effects / Choline / Deoxyribonucleic acid / DNA / DNA biosynthesis / DNA damage / DNA End-Joining Repair - drug effects / DNA repair / DNA Repair - drug effects / DNA Replication - drug effects / Elongation / Fatty acids / Female / Fish Proteins - genetics / Fish Proteins - metabolism / Flame retardants / Flame Retardants - toxicity / Gene Expression Regulation / Health risks / Hepatocytes / Hepatocytes - drug effects / Hepatocytes - metabolism / Humanities and Social Sciences / Humans / Lactic acid / Lipid metabolism / Lipid Metabolism - drug effects / Lipid Metabolism - genetics / Liver / Liver - drug effects / Liver - metabolism / Male / Metabolism / Metabolome - drug effects / Metabolomics / multidisciplinary / Non-homologous end joining / Organophosphates / Organophosphates - toxicity / Peroxisome proliferator-activated receptors / Phosphate / Phosphates / Science / Science (multidisciplinary) / Signal transduction / Toxicity / Transcriptome - drug effects / Water Pollutants, Chemical - toxicity / Zebrafish