1. Long‐term exposure of sucralose induces neuroinflammation and ferroptosis in human microglia cells via SIRT1/NLRP3/IL‐1β/GPx4 signaling pathways.
- Author
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Hacioglu, Ceyhan
- Subjects
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NONNUTRITIVE sweeteners , *SUCRALOSE , *HUMAN cloning , *CELL morphology , *NUCLEAR membranes - 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‐1β (IL‐1β), 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‐1β, 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‐1β, MDA, NLRP3, 8‐OHdG, and caspase 3/7 activity. Sucralose treatment also enhanced microglial activation and neuroinflammation by upregulating IL‐1β 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‐1β/GPx4 pathway in HMC3 cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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