دورية أكاديمية
أعرض في EDS

Label-Free Screening of Drug-Induced Liver Injury Using Stimulated Raman Scattering Microscopy and Spectral Phasor Analysis.

التفاصيل البيبلوغرافية
العنوان: Label-Free Screening of Drug-Induced Liver Injury Using Stimulated Raman Scattering Microscopy and Spectral Phasor Analysis.
المؤلفون: Tipping WJ; Centre for Nanometrology, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow G1 1RD, U.K., Wilson LT; Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, U.K., Tomkinson NCO; Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, U.K., Faulds K; Centre for Nanometrology, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow G1 1RD, U.K., Graham D; Centre for Nanometrology, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow G1 1RD, U.K.
المصدر: Analytical chemistry [Anal Chem] 2024 Jul 02; Vol. 96 (26), pp. 10639-10647. Date of Electronic Publication: 2024 Jun 18.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, American Chemical Society.
مواضيع طبية MeSH: Chemical and Drug Induced Liver Injury*/diagnostic imaging, Humans ; Nonlinear Optical Microscopy/methods ; Spectrum Analysis, Raman/methods ; Propranolol/chemistry ; Hep G2 Cells
مستخلص: Hepatic toxicity is a leading cause of the termination of clinical trials and the withdrawal of therapeutics following regulatory approval. The detection of drug-induced liver injury (DILI) is therefore of importance to ensure patient safety and the effectiveness of novel small molecules and drugs. DILI encompasses drug-induced steatosis (DIS) and drug-induced phospholipidosis (DIPL) which involve the accumulation of excess intracellular lipids. Here, we develop hyperspectral stimulated Raman scattering (SRS) microscopy as a label-free methodology for discriminating DIS and DIPL in mammalian cell culture. We demonstrate that hyperspectral SRS imaging in tandem with spectral phasor analysis is capable of discriminating DIS and DIPL based on the nature and distribution of intracellular lipids resulting from each process. To demonstrate the practical application of this methodology, we develop a panel of alkyne-tagged propranolol analogues that display varying DILI effects. Using hyperspectral SRS imaging together with spectral phasor analysis, our label-free methodology corroborated the standard fluorescence-based assay for DILI. As a label-free screening method, it offers a convenient and expedient methodology for visualizing hepatotoxicity in cell cultures which could be integrated into the early stages of the drug development process for screening new chemical entities for DILI.
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المشرفين على المادة: 9Y8NXQ24VQ (Propranolol)
تواريخ الأحداث: Date Created: 20240618 Date Completed: 20240702 Latest Revision: 20240805
رمز التحديث: 20240806
مُعرف محوري في PubMed: PMC11223099
DOI: 10.1021/acs.analchem.4c01285
PMID: 38889191
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-6882
DOI:10.1021/acs.analchem.4c01285