Long-term exposure of sucralose induces neuroinflammation and ferroptosis in human microglia cells via SIRT1/NLRP3/IL-1β/GPx4 signaling pathways

dc.authoridHacioglu, Ceyhan/0000-0002-0993-6118
dc.contributor.authorHacioglu, Ceyhan
dc.date.accessioned2025-10-11T20:48:50Z
dc.date.available2025-10-11T20:48:50Z
dc.date.issued2024
dc.departmentDüzce Üniversitesien_US
dc.description.abstractMicroglia serve as the primary defense mechanism in the brain. Artificial sweeteners are widely used as dietary supplements, though their long-term effects remain uncertain. In this study, we investigated the effects of sucralose on microglia during prolonged exposure via the neuroinflammatory and ferroptosis pathways. Initially, human microglial clone 3 (HMC3) cells were exposed to sucralose (0-50 mM) for 24, 48, and 72 h to investigate the short-term effects. Subsequently, HMC3 cells were treated with 1 mM sucralose for 7, 14, and 21 days to examine long-term effects. We measured levels of interleukin-1 beta (IL-1 beta), NOD-like receptor protein 3 (NLRP3), 8-hydroxydeoxyguanosine (8-OHdG), Sirtuin-1 (SIRT1), glutathione peroxidase-4 (GPx4), reduced glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe2+), and caspase 3/7. Additionally, we analyzed the impact of sucralose on cell morphology, migration, and expression levels of IL-1 beta, NLRP3, SIRT1, and GPx4. Sucralose inhibited cell viability and proliferation in HMC3 cells in a concentration- and time-dependent manner and induced membrane and nuclear abnormalities. Moreover, sucralose significantly reduced the cell migration rate. Long-term sucralose treatment decreased Fe2+, GPx4, GSH, and SIRT1 levels in HMC3 cells while increasing IL-1 beta, MDA, NLRP3, 8-OHdG, and caspase 3/7 activity. Sucralose treatment also enhanced microglial activation and neuroinflammation by upregulating IL-1 beta and NLRP3 and downregulating SIRT1 and GPx4, thereby inducing ferroptosis and suppressing cell viability. Consequently, high concentrations or long-term sucralose treatment may induce neuroinflammation and ferroptosis by targeting the SIRT1/NLRP3/IL-1 beta/GPx4 pathway in HMC3 cells.en_US
dc.identifier.doi10.1002/fsn3.4488
dc.identifier.endpage9107en_US
dc.identifier.issn2048-7177
dc.identifier.issue11en_US
dc.identifier.pmid39619997en_US
dc.identifier.scopus2-s2.0-85204708382en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage9094en_US
dc.identifier.urihttps://doi.org/10.1002/fsn3.4488
dc.identifier.urihttps://hdl.handle.net/20.500.12684/22128
dc.identifier.volume12en_US
dc.identifier.wosWOS:001318844300001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorHacioglu, Ceyhan
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofFood Science & Nutritionen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzKA_WOS_20250911
dc.subjectartificial sweetenersen_US
dc.subjectferroptosisen_US
dc.subjectmicrogliaen_US
dc.subjectneuroinflammationen_US
dc.subjectNLRP3en_US
dc.subjectsirtuinsen_US
dc.subjectsucraloseen_US
dc.titleLong-term exposure of sucralose induces neuroinflammation and ferroptosis in human microglia cells via SIRT1/NLRP3/IL-1β/GPx4 signaling pathwaysen_US
dc.typeArticleen_US

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