Long-term exposure of sucralose induces neuroinflammation and ferroptosis in human microglia cells via SIRT1/NLRP3/IL-1β/GPx4 signaling pathways
dc.authorid | Hacioglu, Ceyhan/0000-0002-0993-6118 | |
dc.contributor.author | Hacioglu, Ceyhan | |
dc.date.accessioned | 2025-10-11T20:48:50Z | |
dc.date.available | 2025-10-11T20:48:50Z | |
dc.date.issued | 2024 | |
dc.department | Düzce Üniversitesi | en_US |
dc.description.abstract | Microglia 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.doi | 10.1002/fsn3.4488 | |
dc.identifier.endpage | 9107 | en_US |
dc.identifier.issn | 2048-7177 | |
dc.identifier.issue | 11 | en_US |
dc.identifier.pmid | 39619997 | en_US |
dc.identifier.scopus | 2-s2.0-85204708382 | en_US |
dc.identifier.scopusquality | N/A | en_US |
dc.identifier.startpage | 9094 | en_US |
dc.identifier.uri | https://doi.org/10.1002/fsn3.4488 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12684/22128 | |
dc.identifier.volume | 12 | en_US |
dc.identifier.wos | WOS:001318844300001 | en_US |
dc.identifier.wosquality | Q2 | en_US |
dc.indekslendigikaynak | Web of Science | en_US |
dc.indekslendigikaynak | Scopus | en_US |
dc.indekslendigikaynak | PubMed | en_US |
dc.institutionauthor | Hacioglu, Ceyhan | |
dc.language.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.relation.ispartof | Food Science & Nutrition | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.snmz | KA_WOS_20250911 | |
dc.subject | artificial sweeteners | en_US |
dc.subject | ferroptosis | en_US |
dc.subject | microglia | en_US |
dc.subject | neuroinflammation | en_US |
dc.subject | NLRP3 | en_US |
dc.subject | sirtuins | en_US |
dc.subject | sucralose | en_US |
dc.title | Long-term exposure of sucralose induces neuroinflammation and ferroptosis in human microglia cells via SIRT1/NLRP3/IL-1β/GPx4 signaling pathways | en_US |
dc.type | Article | en_US |