{"doi":"10.1093/toxsci/kfu132","title":"Glucosylceramide and Lysophosphatidylcholines as Potential Blood Biomarkers for Drug-Induced Hepatic Phospholipidosis","abstract":null,"journal":"Toxicological Sciences","year":2014,"id":655821,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":367129,"name":"Keiko Maekawa","orcid":"0000-0003-4857-4137","position":1,"is_corresponding":false},{"id":1038432,"name":"Masaki Ishikawa","orcid":"0000-0002-6491-5539","position":2,"is_corresponding":false},{"id":1711956,"name":"Yuya Senoo","orcid":null,"position":3,"is_corresponding":false},{"id":1711957,"name":"Masayo Urata","orcid":null,"position":4,"is_corresponding":false},{"id":1711958,"name":"Mayumi Murayama","orcid":null,"position":5,"is_corresponding":false},{"id":1711960,"name":"Noriyuki Nakatsu","orcid":null,"position":6,"is_corresponding":false},{"id":532031,"name":"Hiroshi Yamada","orcid":"0000-0002-7694-883X","position":7,"is_corresponding":false},{"id":942275,"name":"Yoshiro Saito","orcid":"0000-0002-0559-5889","position":8,"is_corresponding":false},{"id":1592960,"name":"Kosuke Saito","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Glucosylceramide and Lysophosphatidylcholines as Potential Blood Biomarkers for Drug-Induced Hepatic Phospholipidosis","abstract":"Drug-induced phospholipidosis is one of the major concerns in drug development and clinical treatment. The present study involved the use of a nontargeting lipidomic analysis with liquid chromatography-mass spectrometry to explore noninvasive blood biomarkers for hepatic phospholipidosis from rat plasma. We used three tricyclic antidepressants (clomipramine [CPM], imipramine [IMI], and amitriptyline [AMT]) for the model of phospholipidosis in hepatocytes and ketoconazole (KC) for the model of phospholipidosis in cholangiocytes and administered treatment for 3 and 28 days each. Total plasma lipids were extracted and measured. Lipid molecules contributing to the separation of control and drug-treated rat plasma in a multivariate orthogonal partial least squares discriminant analysis were identified. Four lysophosphatidylcholines (LPCs) (16:1, 18:1, 18:2, and 20:4) and 42:1 hexosylceramide (HexCer) were identified as molecules separating control and drug-treated rats in all models of phospholipidosis in hepatocytes. In addition, 16:1, 18:2, and 20:4 LPCs and 42:1 HexCer were identified in a model of hepatic phospholipidosis in cholangiocytes, although LPCs were identified only in the case of 3-day treatment with KC. The levels of LPCs were decreased by drug-induced phospholipidosis, whereas those of 42:1 HexCer were increased. The increase in 42:1 HexCer was much higher in the case of IMI and AMT than in the case of CPM; moreover, the increase induced by IMI was dose-dependent. Structural characterization determining long-chain base and hexose delineated that 42:1 HexCer was d18:1/24:0 glucosylceramide (GluCer). In summary, our study demonstrated that d18:1/24:0 GluCer and LPCs are potential novel biomarkers for drug-induced hepatic phospholipidosis.","is_dataset_classified":null,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24980264","pmcid":"PMC4271040","openalex_id":"https://openalex.org/W2156287436","authors":[],"funders":[{"funder_name":"Intramural NIH HHS","grant_id":"","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"","title":null}],"total_grants":2,"fwci":1.1697,"citation_percentile":0.77941636,"influential_citations":0,"citation_trend":[{"year":2015,"count":4},{"year":2016,"count":1},{"year":2017,"count":4},{"year":2018,"count":5},{"year":2019,"count":1},{"year":2020,"count":5},{"year":2021,"count":4},{"year":2022,"count":2},{"year":2023,"count":6}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/toxsci/article-pdf/141/2/377/16688196/kfu132.pdf","host_type":"journal"},{"url":"https://academic.oup.com/toxsci/article-pdf/141/2/377/16688196/kfu132.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/toxsci/article-pdf/141/2/377/16688196/kfu132.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/toxsci/kfu132","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24980264","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4271040","host_type":"repository"}],"fields_of_study":["Sphingolipid Metabolism and Signaling","Metabolomics and Mass Spectrometry Studies","Liver Disease Diagnosis and Treatment","Amitriptyline","Animals","Bile Ducts","Biomarkers","Chemical and Drug Induced Liver Injury","Chromatography, Liquid","Clomipramine","Discriminant Analysis","Disease Models, Animal","Glucosylceramides","Hepatocytes","Imipramine","Least-Squares Analysis","Liver","Lysophosphatidylcholines","Lysosomal Storage Diseases","Male","Mass Spectrometry","Metabolomics","Multivariate Analysis","Predictive Value of Tests","Rats"],"mesh_terms":["Amitriptyline","Animals","Bile Ducts","Chromatography, Liquid","Clomipramine","Disease Models, Animal","Glucosylceramides","Imipramine","Liver","Lysophosphatidylcholines","Male","Predictive Value of Tests","Mass Spectrometry","Biomarkers","Multivariate Analysis","Discriminant Analysis","Least-Squares Analysis","Lysosomal Storage Diseases","Hepatocytes","Rats","Metabolomics","Chemical and Drug Induced Liver Injury"],"keywords":["Phospholipidosis","Pharmacology","Pharmacokinetics","Drug","Chemistry","Internal medicine","Medicine","Phospholipid","Biochemistry","Membrane","Biomarker","Ketoconazole","Lipidomics","Tricyclic Antidepressant"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T19:01:36.537399Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}