Transcriptomic, proteomic and metabolomic profiling unravel the mechanisms of hepatotoxicity pathway induced by triphenyl phosphate (TPP)

Abstract

Triphenyl phosphate (TPP) has been found in various environmental media and in biota suggesting widespread human exposure. However, there is still insufficient information on the hepatotoxicity mechanisms of health risk exposed to TPP. In this study, TPP could induce human normal liver cell (L02) apoptosis, injury cell ultrastructure and elevate the levels of reactive oxygen species (ROS). The integrated multi-omic (transcriptomic, proteomic, and metabolomic) analysis was used to further investigate the mechanisms. Transcriptomic analysis revealed that TPP exposure markedly affected cell apoptosis, oncogene activation, REDOX homeostasis, DNA damage and repair. Additionally, proteomic analysis found that the related proteins associated with apoptosis, oxidative stress, metabolism and membrane structure were affected. And metabolomic analysis verified that the related metabolic pathways, such as glycolysis, citrate cycle, oxidative phosphorylation, lipid and protein metabolism, were also significantly disrupted. Based on the multi-omic results, a hypothesized network was constructed to discover the key molecular events in response to TPP and illustrate the mechanism of TPP-induced hepatotoxicity in L02 cells. Therefore, molecular responses could be elucidated at multiple biological levels, and multi-omic analysis could provide scientific tools for exploring potential mechanisms of toxicity and chemical risk assessment.