Metabolic alterations in triptolide‐induced acute hepatotoxicity

Abstract

Triptolide, a major active constitute of Tripterygium wilfordii Hook. F, is prescribed for the treatment of autoimmune diseases in China. One of its most severe adverse effects observed in the clinical use is hepatotoxicity, but the mechanism is still unknown. Therefore, the present study applied an LC/MS-based metabolomic analysis to characterize the metabolomic changes in serum and liver induced by triptolide in mice. Mice were administered triptolide by gavage to establish the acute liver injury model, and serum biochemical and liver histological analyses were applied to assess the degree of toxicity. Multivariate data analyses were performed to investigate the metabolic alterations. Potential metabolites were identified using variable importance in the projection values and Student's t-test. A total of 30 metabolites were observed that were significantly changed by triptolide treatment and the abundance of 29 metabolites was correlated with the severity of toxicity. Pathway analysis indicated that the mechanism of triptolide-induced hepatotoxicity was related to alterations in multiple metabolic pathways, including glutathione metabolism, tricarboxylic acid cycle, purine metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism and amino acid metabolism. The current study provides new mechanistic insights into the metabolic alterations that lead to triptolide-induced hepatotoxicity.

Arctiin Antagonizes Triptolide-Induced Hepatotoxicity via Activation of Nrf2 Pathway

“…The accumulated use of TP can result in severe toxicity and side effects on multiple organs especially the liver, kidney, and body system such as the bone marrow and immune and reproductive system. This has limited the clinical use of TP [ 4 ]. The mechanism of TP-induced liver damage has been largely linked to oxidative stress via the instigation of over generation of reactive oxygen species (ROS), anionic peroxides, liver apoptosis, autophagy, depletion, and inhibition of antioxidant enzymes activities [ 5 – 7 ].…”

High‐content analysis boosts identification of the initial cause of triptolide‐induced hepatotoxicity

“…During the last decade, many studies have been carried out to uncover the mechanism of TP‐induced liver injury or hepatotoxicity, particularly at the cellular level. Various new omics technologies, including transcriptomics and metabolomics, have even been adopted (Vliegenthart et al, ; Zhao et al, ). However, the mechanistic explanations for TP‐induced hepatotoxicity still focus on common phenomena or the endpoint events of cell fate, such as oxidative stress, inflammatory reaction, cell cycle arrest and apoptosis (Cao et al, ; Fu et al, ; Meng et al, ; Oliveira et al, ).…”

Optimization of extraction and analytical protocol for mass spectrometry‐based metabolomics analysis of hepatotoxicity

“…Once the liver has been injured by chemicals or drugs, the levels of a series of bile acids will be increased (Luo, Schomaker, Houle, Aubrecht, & Colangelo, 2014;Yamazaki et al, 2013). * p < 0.05, ** p < 0.01, *** p < 0.001 hepatotoxicity models frequently involve changes in amino acid and nucleotide metabolism (Yamazaki et al, 2013;Zhao et al, 2018). * p < 0.05, ** p < 0.01, *** p < 0.001 hepatotoxicity models frequently involve changes in amino acid and nucleotide metabolism (Yamazaki et al, 2013;Zhao et al, 2018).…”

“…Once the liver has been injured by chemicals or drugs, the levels of a series of bile acids will be increased (Luo, Schomaker, Houle, Aubrecht, & Colangelo, 2014;Yamazaki et al, 2013). Furthermore, some hepatotoxicity models frequently involve changes in amino acid and nucleotide metabolism (Yamazaki et al, 2013;Zhao et al, 2018).…”