Metabolomic and genomic evidence for compromised bile acid homeostasis by senecionine, a hepatotoxic pyrrolizidine alkaloid

Aizhen Xiong, Fan Yang, Lianxiang Fang, Li Yang, Yuqi He, Yu-Jui Yvonne Wan, Ying Xu, Meng Qi, Xiuli Wang, Kate Yu, Karl Wah Keung Tsim, Zhengtao Wang

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Pyrrolizidine alkaloids (PAs) are among the most hepatotoxic natural products that produce irreversible injury to humans via the consumption of herbal medicine and honey, and through tea preparation. Toxicity and death caused by PA exposure have been reported worldwide. Metabolomics and genomics provide scientific and systematic views of a living organism and have become powerful techniques for toxicology research. In this study, senecionine hepatotoxicity on rats was determined via a combination of metabolomic and genomic analyses. From the global analysis generated from two omics data, the compromised bile acid homeostasis in vivo was innovatively demonstrated and confirmed. Serum profiling of bile acids was altered with significantly elevated conjugated bile acids after senecionine exposure, which was in accordance with toxicity. Similarly, the hepatic mRNA levels of several key genes associated with bile acid metabolism were significantly changed. This process included cholesterol 7-α hydroxylase, bile acid CoA-amino acid N-acetyltransferase, sodium taurocholate cotransporting polypeptide, organic anion-transporting polypeptides, and multidrug-resistance-associated protein 3. In conclusion, a cross-omics study provides a comprehensive analysis method for studying the toxicity caused by senecionine, which is a hepatotoxic PA. Moreover, the change in bile acid metabolism and the respective transporters may provide a new PA toxicity mechanism.

Original languageEnglish (US)
Pages (from-to)775-786
Number of pages12
JournalChemical Research in Toxicology
Volume27
Issue number5
DOIs
StatePublished - May 19 2014

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

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    Xiong, A., Yang, F., Fang, L., Yang, L., He, Y., Wan, Y-J. Y., Xu, Y., Qi, M., Wang, X., Yu, K., Tsim, K. W. K., & Wang, Z. (2014). Metabolomic and genomic evidence for compromised bile acid homeostasis by senecionine, a hepatotoxic pyrrolizidine alkaloid. Chemical Research in Toxicology, 27(5), 775-786. https://doi.org/10.1021/tx400451q