{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:51:07Z","timestamp":1785883867283,"version":"3.56.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Amanita<\/jats:italic>\n                      poisoning causes 90%\u201395% of global mushroom-related deaths, yet early prognostic biomarkers for\n                      <jats:italic>Amanita<\/jats:italic>\n                      poisoning are lacking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      33 patients with\n                      <jats:italic>Amanita<\/jats:italic>\n                      poisoning were recruited and categorized into survival and death group. Multivariate logistic regression analysis was used to investigate the independent mortality risk factors for\n                      <jats:italic>Amanita<\/jats:italic>\n                      poisoning patients. Untargeted serum metabolomics was performed to screen the differentially expressed metabolites. The quality control samples were used to evaluate the stability and reproducibility of ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS\/MS) analytical system. The prognosis predictive metabolic biomarkers were identified by ROC curve analysis. Correlations between metabolic biomarkers and biochemical indicators were analyzed by Spearman\u2019s correlation analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant differences were observed between the survival and death groups in clinical manifestations\u2014such as gastrointestinal bleeding, dizziness, headache, delirious coma, infection, and shortness of breath\u2014and in biochemical indicators, including alanine transaminase (ALT), aspartate transaminase (AST), prothrombin time and activated partial thromboplastin time (APTT). Metabolomic analysis identified 80 differentially expressed metabolites involved primarily in amino acid and unsaturated fatty acid metabolism. ROC analysis (AUC &amp;gt;0.9) screened nine potential metabolic biomarkers for predicting clinical outcomes: 9,10-Epoxyoctadecenoic acid, Phosphatidylinositol(16:0\/18:2 (9Z,12Z)), N-Acetyl-L-aspartic acid, PI(20:3 (5Z,8Z,11Z)\/18:0), Propionylcarnitine, Proline betaine, 4\u2032-Methyl-(\u2212)-epigallocatechin 3-(4-methyl-gallate), PG (18:1 (11Z)\/22:6 (4Z,7Z,10Z,13Z,16Z,19Z)), and L-Proline. Notably, correlation analysis revealed that 9,10-Epoxyoctadecenoic acid was positively correlated with AST and activated partial thromboplastin time, whereas 4\u2032-Methyl-(\u2212)-epigallocatechin 3-(4-methyl-gallate), N-acetyl-L-aspartic acid, PI(16:0\/18:2 (9Z,12Z)), PI(20:3 (5Z,8Z,11Z)\/18:0), and Propionylcarnitine showed negative correlations with various liver and coagulation parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Serum metabolomics has identified metabolic biomarkers capable of predicting mortality in\n                      <jats:italic>Amanita<\/jats:italic>\n                      poisoning, with significant correlation to liver and coagulation injury. These biomarkers may facilitate early risk stratification and guide targeted therapeutic interventions. Limitations include small sample size and single-center retrospective design, which may restrict result generalizability.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1716911","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T06:48:12Z","timestamp":1765349292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Serum metabolomics identifies novel prognostic biomarkers in amanita poisoning"],"prefix":"10.3389","volume":"16","author":[{"given":"Dan","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianhong","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"170314","DOI":"10.1016\/j.peptides.2020.170314","article-title":"The cyclopeptide -amatoxin induced hepatic injury via the mitochondrial apoptotic pathway associated with oxidative stress","volume":"129","author":"Chen","year":"2020","journal-title":"Peptides"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e2502001","DOI":"10.1002\/smll.202502001","article-title":"Oral plant-derived nanomedicines mitigate acetaminophen-induced liver injury by modulating the gut-liver axis and intestinal microbiota metabolism","volume":"21","author":"Chen","year":"2025","journal-title":"Small"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11894","DOI":"10.1038\/s41598-018-30426-5","article-title":"Peroxisome proliferator-activated receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF\/c-Met\/ERK1\/2 pathways","volume":"8","author":"Cheng","year":"2018","journal-title":"Sci. Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1080\/15563650.2020.1747624","article-title":"Current fatality rate of suspected cyclopeptide mushroom poisoning in the United States","volume":"59","author":"De Olano","year":"2021","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/s40168-025-02172-0","article-title":"Lactiplantibacillus plantarum attenuate gossypol-induced hepatic lipotoxicity by altering intestinal microbiota for enriching microbial tryptophan metabolites in nile tilapia Oreochromis niloticus","volume":"13","author":"Ding","year":"2025","journal-title":"Microbiome"},{"key":"B7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.jmgm.2014.05.002","article-title":"New in silico insights into the inhibition of RNAP II by \u03b1-amanitin and the protective effect mediated by effective antidotes","volume":"51","author":"Garcia","year":"2014","journal-title":"J. Mol. Graph Model"},{"key":"B8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.fct.2015.09.008","article-title":"Amanita phalloides poisoning: mechanisms of toxicity and treatment","volume":"86","author":"Garcia","year":"","journal-title":"Food Chem. Toxicol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1007\/s00204-015-1582-x","article-title":"A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B","volume":"89","author":"Garcia","year":"","journal-title":"Archives Toxicol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"114665","DOI":"10.1016\/j.fct.2024.114665","article-title":"Amanitin-induced variable cytotoxicity in various cell lines is mediated by the different expression levels of OATP1B3","volume":"188","author":"Gong","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1021\/acs.chemrestox.1c00297","article-title":"Autophagy promotes \u03b1-Amanitin-Induced apoptosis of Hepa1-6 liver cells","volume":"35","author":"Gu","year":"2022","journal-title":"Chem. Res. Toxicol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s00204-003-0527-y","article-title":"The hepatocellular bile acid transporter ntcp facilitates uptake of the lethal mushroom toxin ? amanitin","volume":"78","author":"Gundala","year":"2004","journal-title":"Archives Toxicol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"6407","DOI":"10.1002\/alz.14137","article-title":"Neurometabolic topography and associations with cognition in alzheimer's disease: a whole-brain high-resolution 3D MRSI study","volume":"20","author":"Hu","year":"2024","journal-title":"Alzheimers Dement."},{"key":"B14","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3109\/15563659309000374","article-title":"Kinetics of amatoxins in human poisoning: therapeutic implications","volume":"31","author":"Jaeger","year":"1993","journal-title":"J. Toxicol. Clin. Toxicol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/s0041-0101(03)00238-1","article-title":"Cytotoxic fungi--an overview","volume":"42","author":"Karlson-Stiber","year":"2003","journal-title":"Toxicon"},{"key":"B17","doi-asserted-by":"publisher","first-page":"13028","DOI":"10.3390\/ijms252313028","article-title":"Amanita phalloides-associated liver failure: molecular mechanisms and management","volume":"25","author":"Kayes","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.3748\/wjg.v23.i7.1262","article-title":"Predictors of poor outcomes in patients with wild mushroom-induced acute liver injury","volume":"23","author":"Kim","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"103051","DOI":"10.1016\/j.copbio.2023.103051","article-title":"N-acetyl-aspartate metabolism at the interface of cancer, immunity, and neurodegeneration","volume":"85","author":"Krause","year":"2024","journal-title":"Curr. Opin. Biotechnol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3390\/toxins13060417","article-title":"Toxic effects of amanitins: repurposing toxicities toward new therapeutics","volume":"13","author":"Le Dar\u00e9","year":"2021","journal-title":"Toxins"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2376","DOI":"10.1210\/endo.143.6.8834","article-title":"Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation","volume":"143","author":"Lecka-Czernik","year":"2002","journal-title":"Endocrinology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/bcpt.13858","article-title":"Cyclopeptide mushroom poisoning: a retrospective series of 204 patients","volume":"132","author":"Lecot","year":"2023","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1093\/toxsci\/kfj141","article-title":"Molecular characterization and inhibition of amanitin uptake into human hepatocytes","volume":"91","author":"Letschert","year":"2006","journal-title":"Toxicol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1093\/brain\/awaa264","article-title":"Fast high-resolution metabolic imaging of acute stroke with 3D magnetic resonance spectroscopy","volume":"143","author":"Li","year":"2020","journal-title":"Brain"},{"key":"B25","doi-asserted-by":"publisher","first-page":"518","DOI":"10.46234\/ccdcw2021.134","article-title":"Mushroom poisoning outbreaks - china, 2010-2020","volume":"3","author":"Li","year":"2021","journal-title":"China CDC Wkly."},{"key":"B26","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/0049-38487590137-1","article-title":"Phospholipid requirements of tissue thromboplastin in blood coagulation","volume":"7","author":"Liu","year":"1975","journal-title":"Thromb. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1080\/15563650.2020.1784428","article-title":"N-acetylcysteine as a treatment for amatoxin poisoning: a systematic review","volume":"58","author":"Liu","year":"2020","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"4562","DOI":"10.1039\/d0ay00968g","article-title":"Metabolic profiling of rats poisoned with paraquat and treated with xuebijing using a UPLC-QTOF-MS\/MS metabolomics approach","volume":"12","author":"Liu","year":"2020","journal-title":"Anal. Methods"},{"key":"B29","doi-asserted-by":"publisher","first-page":"107153","DOI":"10.1016\/j.toxicon.2023.107153","article-title":"Serum metabolomic analyses reveal the potential metabolic biomarkers for prediction of amatoxin poisoning","volume":"230","author":"Liu","year":"2023","journal-title":"Toxicon"},{"key":"B30","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00726-012-1361-4","article-title":"Taurine and inflammatory diseases","volume":"46","author":"Marcinkiewicz","year":"2014","journal-title":"Amino Acids"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1007\/s00726-017-2494-2","article-title":"The role of methionine on metabolism, oxidative stress, and diseases","volume":"49","author":"Mart\u00ednez","year":"2017","journal-title":"Amino Acids"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.2174\/138920112802273353","article-title":"Legalon\u00ae SIL: the antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning","volume":"13","author":"Mengs","year":"2012","journal-title":"Curr. Pharm. Biotechnol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1093\/nar\/24.15.2924","article-title":"In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin","volume":"24","author":"Nguyen","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1093\/brain\/awx331","article-title":"Neurochemical changes in the medial wall of the brain in chronic migraine","volume":"141","author":"Niddam","year":"2018","journal-title":"Brain"},{"key":"B35","doi-asserted-by":"publisher","first-page":"639","DOI":"10.3390\/toxins12100639","article-title":"Toxic potential of traditionally consumed mushroom Species-A controversial continuum with many unanswered questions","volume":"12","author":"Nieminen","year":"2020","journal-title":"Toxins (Basel)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1016\/j.juro.2009.08.085","article-title":"Phosphatidylinositol-3-kinase\/Akt signaling pathway and kidney cancer, and the therapeutic potential of phosphatidylinositol-3-kinase\/Akt inhibitors","volume":"182","author":"Porta","year":"2009","journal-title":"J. Urol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.aohep.2019.04.008","article-title":"Current concepts in acute liver failure","volume":"18","author":"Rovegno","year":"2019","journal-title":"Ann. Hepatol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1148\/radiol.2018172083","article-title":"Changes in brain metabolite concentrations after neonatal hypoxic-ischemic encephalopathy","volume":"288","author":"Shibasaki","year":"2018","journal-title":"Radiology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.3390\/nu13093229","article-title":"Vitamin B6 in health and disease","volume":"13","author":"Stach","year":"2021","journal-title":"Nutrients"},{"key":"B40","doi-asserted-by":"publisher","first-page":"215","DOI":"10.3390\/toxins10060215","article-title":"Effect of biliary drainage on the toxicity and toxicokinetics of Amanita exitialis in beagles","volume":"10","author":"Sun","year":"2018","journal-title":"Toxins"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1080\/15563650.2022.2098139","article-title":"Amanitin intoxication: effects of therapies on clinical outcomes - a review of 40 years of reported cases","volume":"60","author":"Tan","year":"2022","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B42","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3109\/15563650.2011.565772","article-title":"Clinical features and outcome of patients with amatoxin-containing mushroom poisoning","volume":"49","author":"Trabulus","year":"2011","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2025.0577","article-title":"Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-HT production","author":"Tu","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1038\/s41467-023-37714-3","article-title":"Identification of indocyanine green as a STT3B inhibitor against mushroom alpha-amanitin cytotoxicity","volume":"14","author":"Wang","year":"2023","journal-title":"Nat. Commun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3109\/10409237809149870","article-title":"Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous amanita mushrooms","volume":"5","author":"Wieland","year":"2008","journal-title":"CRC Crit. Rev. Biochem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.toxlet.2023.06.004","article-title":"\u03b1-amanitin induces autophagy through AMPK-mTOR-ULK1 signaling pathway in hepatocytes","volume":"383","author":"Xu","year":"2023","journal-title":"Toxicol. Lett."},{"key":"B47","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s00204-022-03396-x","article-title":"Mechanism and treatment of \u03b1-amanitin poisoning","volume":"97","author":"Xue","year":"2023","journal-title":"Arch. Toxicol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"108423","DOI":"10.1016\/j.toxicon.2025.108423","article-title":"Ezetimibe protects against alpha-amanitin-induced hepatotoxicity by targeting the NTCP receptor: mechanistic insights from in vitro and in vivo models","volume":"264","author":"Xue","year":"2025","journal-title":"Toxicon"},{"key":"B49","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1111\/j.1440-1746.2008.05370.x","article-title":"Role of peroxisome proliferator-activated receptor-gamma (PPARgamma) during liver regeneration in rats","volume":"23","author":"Yamamoto","year":"2008","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jcrc.2018.03.028","article-title":"Management of Amanita phalloides poisoning: a literature review and update","volume":"46","author":"Ye","year":"2018","journal-title":"J. Crit. Care"},{"key":"B51","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ajem.2020.01.027","article-title":"CLIF-OF 9 predicts poor outcome in patients with Amanita phalloides poisoning","volume":"39","author":"Ye","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1111\/jgh.16676","article-title":"Effect of Rab18 on liver injury and lipid accumulation by regulating perilipin 2 and peroxisome proliferator-activated receptor gamma in non-alcoholic fatty liver disease","volume":"39","author":"Zhang","year":"2024","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e37320","DOI":"10.1016\/j.heliyon.2024.e37320","article-title":"Establishment and validation of a nomogram model for prediction of clinical outcomes in patients with Amanita phalloides poisoning","volume":"10","author":"Zhang","year":"2024","journal-title":"Heliyon"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.3390\/metabo13111164","article-title":"Metabolomic insights into the mechanisms of ganoderic acid: protection against \u03b1-Amanitin-Induced liver injury","volume":"13","author":"Zheng","year":"2023","journal-title":"Metabolites"},{"key":"B55","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1080\/15563650.2021.1887492","article-title":"Intravenous rifampicin use in the management of amanita phalloides toxicity","volume":"59","author":"Zuker-Herman","year":"2021","journal-title":"Clin. Toxicol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1716911\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T06:48:14Z","timestamp":1765349294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1716911\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":53,"alternative-id":["10.3389\/fphar.2025.1716911"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1716911","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]},"article-number":"1716911"}}