Esculetin Protects Human Retinal Pigment Epithelial Cells from Lipopolysaccharide-induced Inflammation and Cell Death

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dc.authoridGüçlü, Hande/0000-0002-3021-0493
dc.authoridOzal, Sadik Altan/0000-0003-0078-1049
dc.authoridERDOGAN, SUAT/0000-0002-6823-6293
dc.authorwosidGüçlü, Hande/AAW-9756-2020
dc.authorwosidOzal, Sadik Altan/B-5123-2019
dc.contributor.authorOzal, S. Altan
dc.contributor.authorTurkekul, Kader
dc.contributor.authorGurlu, Vuslat
dc.contributor.authorGuclu, Hande
dc.contributor.authorErdogan, Suat
dc.date.accessioned2024-06-12T11:01:30Z
dc.date.available2024-06-12T11:01:30Z
dc.date.issued2018
dc.departmentTrakya Üniversitesien_US
dc.description.abstractPurpose: Age-related macular degeneration (AMD) is the most common cause of visual loss. The dry AMD is characterized by retinal pigment epithelium (RPE) death and changes in AMD lead to severe loss of vision. Coumarin-derived esculetin has a number of therapeutic and pharmacological effects such as anti-inflammatory and antioxidant with various mechanisms. The purpose of this study was to investigate the effects of esculetin treatment on lipopolysaccharide (LPS)-induced inflammation, oxidative stress, and cell survival.Material and methods: Human RPE cells (ARPE-19) were incubated for 24-72h with 5g/ml LPS to induce inflammation and oxidative stress. Esculetin (5 M) was used to protect the cells from LPS-induced damage. The cell viability was evaluated by quantitative 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Interleukin 6 (IL-6), IL-12, and vascular endothelial growth factor (VEGF) levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1, tumor necrosis factor receptor (TNFR), TNF-related apoptosis-inducing ligand (TRAIL), catalase, glutathione peroxidase (GPx), superoxide dismutase 1 (CuZnSOD) and SOD2 (MnSOD) mRNA expressions were analyzed by RT-quantitative polymerase chain reaction. Apoptosis was monitored by cell-based cytometer. NF-kappa B (NF-B) p65/RelA levels were determined by ELISA, and NF-B protein expression and extracellular signal-regulated kinase (ERK1/2) phosphorylation were evaluated by Western blot analysis.Results: Esculetin treatment significantly suppressed LPS-induced cell death mediated by apoptosis and necrosis in a concentration-dependent manner. While LPS caused significant inflammation with cytokine increase in cells, esculetin reduced the expression of LPS-induced cytokines, VEGF, TNFR, and TRAIL. Furthermore, exposure to LPS increased the expression of GPx and mitochondrial MnSOD, leading to oxidative stress in the cells. Esculetin treatment attenuated phosphorylation of ERK1/2 and NF-B expression mediated by LPS.Conclusions: These results suggest that esculetin may be an alternative treatment option for endotoxin-induced inflammation and oxidative stress, which therefore may inhibit the development of LPS-mediated AMD.en_US
dc.identifier.doi10.1080/02713683.2018.1481517
dc.identifier.endpage1176en_US
dc.identifier.issn0271-3683
dc.identifier.issn1460-2202
dc.identifier.issue9en_US
dc.identifier.pmid29806490en_US
dc.identifier.scopus2-s2.0-85048123708en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1169en_US
dc.identifier.urihttps://doi.org/10.1080/02713683.2018.1481517
dc.identifier.urihttps://hdl.handle.net/20.500.14551/20905
dc.identifier.volume43en_US
dc.identifier.wosWOS:000441995900013en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Incen_US
dc.relation.ispartofCurrent Eye Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectEsculetinen_US
dc.subjectARPE-19 Cellsen_US
dc.subjectAge-Related Macular Degenerationen_US
dc.subjectInflammationen_US
dc.subjectLipopolysaccharideen_US
dc.subjectMacular Degenerationen_US
dc.subjectOxidative Stressen_US
dc.subjectHydrogen-Peroxideen_US
dc.subjectDiabetic-Ratsen_US
dc.subjectExpressionen_US
dc.subjectActivationen_US
dc.subjectPathwayen_US
dc.subjectInductionen_US
dc.subjectCytokinesen_US
dc.subjectVegfen_US
dc.titleEsculetin Protects Human Retinal Pigment Epithelial Cells from Lipopolysaccharide-induced Inflammation and Cell Deathen_US
dc.typeArticleen_US

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