ArticleChemical research in toxicology2014
Metabolomic and genomic evidence for compromised bile acid homeostasis by senecionine, a hepatotoxic pyrrolizidine alkaloid.
Article in Chemical research in toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Potential Hepatotoxins Found in Herbal Medicinal Products: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Additive hepatotoxicity of seneciphylline and lasiocarpine mixtures: multi-omics insights into P53 driven apoptosis and a Warburg-like metabolic reprogramming.Archives of toxicology · 2026Article
- Pyrrolizidine Alkaloid-Induced Hepatotoxicity: A Narrative Review on Molecular Mechanisms and Detoxification Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Chlorogenic acid attenuates pyrrolizidine alkaloid-induced liver injury through modulation of the SIRT1/FXR signaling pathway.Chinese medicine · 2025Article
- Review
- Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.Archives of toxicology · 2024Article
- Serum metabolomics strategy for investigating the hepatotoxicity induced by different exposure times and doses ofRSC advances · 2023Article
- Hepatotoxic mechanism of cantharidin: insights and strategies for therapeutic intervention.Frontiers in pharmacology · 2023Review
- Monocrotaline Toxicity Alters the Function of Hepatocyte Membrane Transporters in Rats.International journal of molecular sciences · 2022Article
- Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids.Archives of toxicology · 2021Review
- Role of liver sinusoidal endothelial cells in liver diseases.Nature reviews. Gastroenterology & hepatology · 2021Review
- The Food Contaminants Pyrrolizidine Alkaloids Disturb Bile Acid Homeostasis Structure-Dependently in the Human Hepatoma Cell Line HepaRG.Foods (Basel, Switzerland) · 2021Article
- Pyrrolizidine Alkaloids Disturb Bile Acid Homeostasis in the Human Hepatoma Cell Line HepaRG.Foods (Basel, Switzerland) · 2021Article
- Mechanism of Paeoniflorin on ANIT-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology.Frontiers in pharmacology · 2021Article
- High Dietary Kuding Tea Extract Supplementation Induces Hepatic Xenobiotic-Metabolizing Enzymes-A 6-Week Feeding Study in Mice.Nutrients · 2019Article
- Inhibition of Drp1 protects against senecionine-induced mitochondria-mediated apoptosis in primary hepatocytes and in mice.Redox biology · 2017Article
- Article
- Research Advances on Hepatotoxicity of Herbal Medicines in China.BioMed research international · 2016Review
- Ginseng alleviates cyclophosphamide-induced hepatotoxicity via reversing disordered homeostasis of glutathione and bile acid.Scientific reports · 2015Article
Corrections and comments
- Erratum issuedWan, Yvonne Yu-Jui [corrected to Wan, Yu-Jui Yvonne]
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
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.
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