Long-term exposure of sucralose induces neuroinflammation and ferroptosis in human microglia cells via SIRT1/NLRP3/IL-1β/GPx4 signaling pathways
Küçük Resim Yok
Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
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.
Açıklama
Anahtar Kelimeler
artificial sweeteners, ferroptosis, microglia, neuroinflammation, NLRP3, sirtuins, sucralose
Kaynak
Food Science & Nutrition
WoS Q Değeri
Q2
Scopus Q Değeri
N/A
Cilt
12
Sayı
11
