Original Research

Exp. Biol. Med.

Sec. Anatomy/Pathology

Volume 250 - 2025 | doi: 10.3389/ebm.2025.10607

This article is part of the Issue2024 International Conference on Neuroprotective Agents Conference ProceedingsView all 12 articles

Assessing the Developmental Effects of Fentanyl (Anesthetics/Analgesics) and Impacts on Lipidomic Profiling Using Neural Stem Cell Models

Cheng  WangCheng Wang1*Jinchun  SunJinchun Sun2Rohini  DonakondaRohini Donakonda2Richard  BegerRichard Beger2Leah  E LathamLeah E Latham1Leihong  WuLeihong Wu3Shuliang  LiuShuliang Liu1Joseph  P HanigJoseph P Hanig4Fang  LiuFang Liu1
  • 1Division of Neurotoxicology, National Center for Toxicological Research (FDA), Jefferson, United States
  • 2Division of Systems Biology, National Center for Toxicological Research (FDA), Jefferson, United States
  • 3Division of Bioinformatics and Biostatistics, National Center for Toxicological Research (FDA), Jefferson, United States
  • 4Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States

The final, formatted version of the article will be published soon.

Background: Fentanyl is a potent and short-acting opioid that is often given to pediatric patients during surgery to relieve pain and as an adjunct to anesthesia. Its effects on the developing brain are yet to be determined. In the present study, commercially available human neural stem cells (NSCs) were used to model the effects of fentanyl on the developing human brain.Methods: We determined the dose dependent effects and temporal relationships between fentanyl exposures and NSC health, viability, and differentiation. Markers of mitochondrial health [3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetra-zolium bromide (MTT)] and cell death/damage [lactate dehydrogenase (LDH)] were monitored to determine the dose response effects of fentanyl on NSC viability. In addition, lipidomics analysis was conducted to investigate lipid profile changes in differentiated neural cells treated with fentanyl.Results: Fentanyl did not cause a significant increase in LDH release, nor MTT reduction after 24-h exposure at concentrations of 0.5, 1.0, 3.0, 10, or 100 µM, for both NSCs and differentiated neural cells. Lipidomics data showed the top 15 most variable important in projection (VIP) lipid species (the higher the VIP scores, the bigger changes in treated groups vs. controls), including lysophosphatidylcholines (LPCs), lysophosphatidylethanolamines (LPEs), ceramides (CER), cholesterol esters (ChEs) and sphingosine (SPH). The lipidomic data indicate that LPC (16:0), LPC (16:1), LPC (18:1), CER (d18:0_22:0), CER (d18:2_18:0), CER(d18:2_24:1) were significantly increased, and only ChE (24:5) and SPH (d18:1) were significantly decreased in the highest dose group versus control.Conclusions: These data indicated that fentanyl exposure (24-h) did not induce detectable cell death. However, a lipidomic analysis indicated that fentanyl may affect immature neural cell functions through modifying lipid composition and lipid metabolism. These data indicated that despite the absence of clear neurodegeneration, fentanyl may still have a negative impact on the developing brain.

Keywords: Development, Fentanyl, Lipidomic analysis, Anesthetics, neurotoxicity

Received: 28 Mar 2025; Accepted: 28 May 2025.

Copyright: © 2025 Wang, Sun, Donakonda, Beger, Latham, Wu, Liu, Hanig and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Cheng Wang, Division of Neurotoxicology, National Center for Toxicological Research (FDA), Jefferson, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.