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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Propofol and fospropofol are used in pediatric surgical anesthesia, but their comparative developmental safety remains uncertain. In this study, zebrafish embryos were exposed to equianesthetic concentrations of propofol or fospropofol. Embryonic survival, hatching, malformation, and post-anesthesia motor behavior were assessed. RNA sequencing and molecular docking were performed to explore potential molecular mechanisms. Fospropofol exhibited lower developmental toxicity than propofol, as shown by the higher survival and hatching rates and a lower malformation rate. Comparative toxicogenomic analysis revealed distinct molecular pathways and candidate targets that may underlie these differential effects. Collectively, these zebrafish data suggest a favorable developmental safety profile for fospropofol and underscore the need for dose optimization and monitoring in pediatric anesthetic management; validation in mammalian models and controlled human studies is further warranted.<\/jats:p>","DOI":"10.3390\/ijms27198494","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:36:07Z","timestamp":1790166967000},"page":"8494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential\u00a0Neurodevelopmental Toxicity of Propofol and Fospropofol: Mechanistic Insights and Potential Clinical Implications\u2014A Zebrafish Model Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7137-1883","authenticated-orcid":false,"given":"Zhe","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated 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Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.bja.2017.11.107","article-title":"Systematic review of the neurocognitive outcomes used in studies of paediatric anaesthesia neurotoxicity","volume":"120","author":"Clausen","year":"2018","journal-title":"Br. J. Anaesth."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1523\/JNEUROSCI.23-03-00876.2003","article-title":"Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits","volume":"23","author":"Hartman","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.braindev.2009.11.011","article-title":"Unexpected neurological sequelae following propofol anesthesia in infants: Three case reports","volume":"32","author":"Meyer","year":"2010","journal-title":"Brain Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"l6459","DOI":"10.1136\/bmj.l6459","article-title":"Does general anesthesia affect neurodevelopment in infants and children?","volume":"367","author":"McCann","year":"2019","journal-title":"Bmj"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1021\/acschemneuro.2c00755","article-title":"Propofol-Induced Developmental Neurotoxicity: From Mechanisms to Therapeutic Strategies","volume":"14","author":"Zhang","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7857","DOI":"10.1021\/acs.jmedchem.0c00698","article-title":"Design, Synthesis, and Activity Study of Water-Soluble, Rapid-Release Propofol Prodrugs","volume":"63","author":"Liu","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.2174\/138161212803832308","article-title":"Fospropofol, a new sedative anesthetic, and its utility in the perioperative period","volume":"18","author":"Abdelmalak","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2165\/11204450-000000000-00000","article-title":"Fospropofol","volume":"70","author":"Scott","year":"2010","journal-title":"Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Vorhees, C.V., Williams, M.T., Hawkey, A.B., and Levin, E.D. (2021). Translating Neurobehavioral Toxicity Across Species from Zebrafish to Rats to Humans: Implications for Risk Assessment. Front. Toxicol., 3.","DOI":"10.3389\/ftox.2021.629229"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/toxsci\/kfy044","article-title":"Making Waves: New Developments in Toxicology with the Zebrafish","volume":"163","author":"Horzmann","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1534\/genetics.116.190843","article-title":"Learning to Fish with Genetics: A Primer on the Vertebrate Model Danio rerio","volume":"203","author":"Holtzman","year":"2016","journal-title":"Genetics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The zebrafish reference genome sequence and its relationship to the human genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20120462","DOI":"10.1098\/rstb.2012.0462","article-title":"Zebrafish forebrain and temporal conditioning","volume":"369","author":"Cheng","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.nbd.2010.05.010","article-title":"The comparative neuroanatomy and neurochemistry of zebrafish CNS systems of relevance to human neuropsychiatric diseases","volume":"40","author":"Panula","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"133033","DOI":"10.1016\/j.chemosphere.2021.133033","article-title":"Zebrafish (Danio rerio): A potential model to assess developmental toxicity of ketamine","volume":"291","author":"Huang","year":"2022","journal-title":"Chemosphere"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s12035-021-02559-8","article-title":"Midazolam Exposure Impedes Oligodendrocyte Development via the Translocator Protein and Impairs Myelination in Larval Zebrafish","volume":"59","author":"Xu","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/jat.3183","article-title":"Zebrafish as a model for studying the developmental neurotoxicity of propofol","volume":"35","author":"Guo","year":"2015","journal-title":"J. Appl. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15789","DOI":"10.1038\/s41598-020-72669-1","article-title":"A vertebrate model to reveal neural substrates underlying the transitions between conscious and unconscious states","volume":"10","author":"Bedell","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1097\/ALN.0000000000002963","article-title":"Drug-selective Anesthetic Insensitivity of Zebrafish Lacking \u03b3-Aminobutyric Acid Type A Receptor \u03b23 Subunits","volume":"131","author":"Yang","year":"2019","journal-title":"Anesthesiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"150210","DOI":"10.1016\/j.scitotenv.2021.150210","article-title":"A systematic comparison of neurotoxicity of bisphenol A and its derivatives in zebrafish","volume":"805","author":"Gu","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6125","DOI":"10.1038\/s41380-021-01179-x","article-title":"Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons","volume":"26","author":"Runge","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"RP90025","DOI":"10.7554\/eLife.90025.3","article-title":"Deciphering the genetic interactions between Pou4f3, Gfi1, and Rbm24 in maintaining mouse cochlear hair cell survival","volume":"12","author":"Wang","year":"2024","journal-title":"Elife"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1111\/gtc.12509","article-title":"Medaka and zebrafish contactin1 mutants as a model for understanding neural circuits for motor coordination","volume":"22","author":"Takeuchi","year":"2017","journal-title":"Genes Cells"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e135697","DOI":"10.1172\/jci.insight.135697","article-title":"Mutations of CNTNAP1 led to defects in neuronal development","volume":"5","author":"Li","year":"2020","journal-title":"JCI Insight"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1126\/science.1519064","article-title":"SV2, a brain synaptic vesicle protein homologous to bacterial transporters","volume":"257","author":"Bajjalieh","year":"1992","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/cne.25238","article-title":"Expression and distribution of synaptotagmin family members in the zebrafish retina","volume":"530","author":"Henry","year":"2022","journal-title":"J. Comp. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"a017384","DOI":"10.1101\/cshperspect.a017384","article-title":"Leber congenital amaurosis caused by mutations in RPGRIP1","volume":"5","author":"Li","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1194\/jlr.M100343-JLR200","article-title":"HPLC-MS\/MS analysis of the products generated from all-trans-retinoic acid using recombinant human CYP26A","volume":"43","author":"Chithalen","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.apsb.2019.11.016","article-title":"New insights of CYP1A in endogenous metabolism: A focus on single nucleotide polymorphisms and diseases","volume":"10","author":"Lu","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/s41418-019-0412-8","article-title":"Histone methyltransferase G9a protects against acute liver injury through GSTP1","volume":"27","author":"Zhang","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40246-024-00593-w","article-title":"Zebrafish as a model to investigate a biallelic gain-of-function variant in MSGN1, associated with a novel skeletal dysplasia syndrome","volume":"18","author":"Koparir","year":"2024","journal-title":"Hum. Genom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jhep.2021.01.042","article-title":"FOXA3 induction under endoplasmic reticulum stress contributes to non-alcoholic fatty liver disease","volume":"75","author":"Liu","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s00401-024-02721-1","article-title":"Rare genetic variation in fibronectin 1 (FN1) protects against APOE\u03b54 in Alzheimer\u2019s disease","volume":"147","author":"Bhattarai","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/imr.13092","article-title":"Unique aspects of IFN-\u03b3\/STAT1 signaling in neurons","volume":"311","author":"Clark","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"156626","DOI":"10.1016\/j.phymed.2025.156626","article-title":"Naoqing formula alleviates cerebral ischemia\/reperfusion injury induced inflammatory injury by regulating Csf3 mediated JAK\/STAT pathway and macrophage polarization","volume":"140","author":"Ye","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1158\/2159-8290.CD-24-0634","article-title":"DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2\/p300-Mediated Transcriptional Reprogramming","volume":"15","author":"Gritti","year":"2025","journal-title":"Cancer Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/ng.3375","article-title":"Genomic spectra of biliary tract cancer","volume":"47","author":"Nakamura","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1182\/blood-2014-01-551820","article-title":"A new form of macrothrombocytopenia induced by a germ-line mutation in the PRKACG gene","volume":"124","author":"Manchev","year":"2014","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1097\/HEP.0000000000001007","article-title":"Drug interaction with UDP-Glucuronosyltransferase (UGT) enzymes is a predictor of drug-induced liver injury","volume":"81","author":"Olubamiwa","year":"2025","journal-title":"Hepatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1152\/physrev.00005.2019","article-title":"Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease","volume":"100","author":"Talavera","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1021\/acs.est.0c05724","article-title":"Developmental Toxicity of Few-Layered Black Phosphorus toward Zebrafish","volume":"55","author":"Yang","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1146\/annurev-pharmtox-010611-134751","article-title":"Systematic approaches to toxicology in the zebrafish","volume":"52","author":"Peterson","year":"2012","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12495","DOI":"10.1021\/acs.est.4c14490","article-title":"Small Black Phosphorus Disrupts Vascular Development and Hematopoiesis in Zebrafish Larvae","volume":"59","author":"Zhang","year":"2025","journal-title":"Environ. Sci. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"105293","DOI":"10.1016\/j.envint.2019.105293","article-title":"Early-life exposure to the organophosphorus flame-retardant tris (1,3-dichloro-2-propyl) phosphate induces delayed neurotoxicity associated with DNA methylation in adult zebrafish","volume":"134","author":"Li","year":"2020","journal-title":"Environ. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"170131","DOI":"10.1016\/j.scitotenv.2024.170131","article-title":"Neurotoxic effects of 2-ethylhexyl diphenyl phosphate exposure on zebrafish larvae: Insight into inflammation-driven changes in early motor behavior","volume":"915","author":"Ni","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-022-01225-2","article-title":"SCGN deficiency is a risk factor for autism spectrum disorder","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1021\/acs.est.3c05282","article-title":"Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut\u2013Brain Regulation in Zebrafish","volume":"58","author":"Mu","year":"2024","journal-title":"Environ. Sci. Technol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"117911","DOI":"10.1016\/j.ecoenv.2025.117911","article-title":"Exploring the mechanisms of lithium neurotoxicity based on network toxicology and molecular docking","volume":"292","author":"Wei","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"167904","DOI":"10.1016\/j.scitotenv.2023.167904","article-title":"Efficient analysis of toxicity and mechanisms of environmental pollutants with network toxicology and molecular docking strategy: Acetyl tributyl citrate as an example","volume":"905","author":"Huang","year":"2023","journal-title":"Sci. Total Environ."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:27:45Z","timestamp":1790310465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":54,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198494"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198494","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]}}}