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- W4312209753 endingPage "113586" @default.
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- W4312209753 abstract "Oxidative stress is the central pathomechanism in multiple cell death pathways, including ferroptosis, a form of iron-dependent programmed cell death. Various phytochemicals, which include the inducers of the nuclear factor erythroid-2-related factor 2-antioxidant response element (Nrf2-ARE) transcription pathway, prevent ferroptosis. We recently reported that several compounds, such as the potent Nrf2-ARE inducer curcumin, protect mouse hippocampus-derived HT22 cells against ferroptosis independently of Nrf2-ARE activity. The present study characterized the anti-ferroptotic mechanisms of two additional Nrf2-ARE inducers, quercetin and resveratrol. Both compounds prevented erastin- and RSL3-induced ferroptosis of wild-type HT22 cells, and also blocked the exacerbated erastin- and RSL3-induced ferroptosis of Nrf2-knockdown HT22 cells. In both HT22 cells, quercetin and resveratrol blocked erastin- and RSL3-induced elevation in reactive oxygen species. These results suggest that the Nrf2-ARE pathway does protect against ferroptosis, but quercetin and resveratrol act by reducing oxidative stress independently of Nrf2-ARE induction. Quercetin and resveratrol also reduced Fe2+ concentrations in HT22 cells and in cell-free reactions. Thus, quercetin and resveratrol likely protect against erastin- and RSL3-induced ferroptosis by inhibiting the iron-catalyzed generation of hydroxyl radicals. Unlike quercetin, resveratrol cannot form a chelate structure with Fe2+ but the density functional theory computation demonstrates that resveratrol can form stable monodentate complexes with the alkene moiety and the electron-rich A ring." @default.
- W4312209753 created "2023-01-04" @default.
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- W4312209753 date "2023-02-01" @default.
- W4312209753 modified "2023-10-16" @default.
- W4312209753 title "Quercetin and resveratrol inhibit ferroptosis independently of Nrf2–ARE activation in mouse hippocampal HT22 cells" @default.
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- W4312209753 doi "https://doi.org/10.1016/j.fct.2022.113586" @default.
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