Nervonoylceramide (C24:1Cer), a lipid biomarker for ocular irritants released from the 3D reconstructed human cornea-like epithelium, MCTT HCE™
Autor: | Su Hyon Lee, Kyung Min Lim, Young-Jin Chun, Seol Yeong Kim, Seunghye Choi, Kyung Mi Joo, Dalwoong Choi, Miri Lee |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cell Survival Fatty Acid Elongases Octoxynol Detergents Biology Animal Testing Alternatives Ceramides Toxicology Excipients Fatty Acids Monounsaturated 03 medical and health sciences chemistry.chemical_compound Benzalkonium chloride 0302 clinical medicine Acetyltransferases In vivo Cornea Toxicity Tests Lipidomics medicine Humans Metabolomics Cells Cultured Molecular Structure Tissue Engineering Epithelium Corneal Nile red Sodium Dodecyl Sulfate General Medicine Lipid Metabolism In vitro Epithelium Staining 030104 developmental biology medicine.anatomical_structure chemistry Biochemistry Enzyme Induction 030220 oncology & carcinogenesis Irritants sense organs Benzalkonium Compounds Biomarkers Stearoyl-CoA Desaturase medicine.drug |
Zdroj: | Toxicology in Vitro. 47:94-102 |
ISSN: | 0887-2333 |
DOI: | 10.1016/j.tiv.2017.11.008 |
Popis: | Due to invasive and painful procedures during in vivo rabbit eye irritation test, in vitro alternative methods have been widely investigated. Recently, 3D reconstructed human cornea-like epitheliums (RhCEs) garner a huge attention. RhCEs employ the tissue viability as a primary endpoint to determine ocular irritancy but additional biomarkers may improve its predictive capacity. Here, we explored lipid biomarkers for ocular irritants in MCTT HCE™ RhCE model. Three irritants; sodium lauryl sulfate, benzalkonium chloride and triton X-100 were selected to represent anionic, cationic and non-ionic detergent respectively. After treating MCTT HCE™ with irritants, the alteration of lipids in the treated tissues was examined with Nile Red staining, which revealed the depletion of corneal lipids. We further quantitated the release of ceramides and free fatty acids, major lipid components of cornea, into the medium during the post-treatment incubation, employing a sensitive UPLC-MS/MS method. Among 44 lipid species, nervonoylceramide (C24:1Cer) was found to be released commonly by all three irritants in a concentration-dependent manner. Tests with 10 additional reference substances further supported that C24:1Cer release was significantly correlated with viability. Examination of the genes involved in the biosynthetic pathway for C24:1Cer revealed that stearoylCoA desaturase (SCD) and elongase1 (ELOVL1) were upregulated, suggesting that lipids and related genes may be employed as biomarkers for ocular irritants. |
Databáze: | OpenAIRE |
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