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Intracellular glutathione peroxidase 4 (GPX4) uses reduced glutathione (GSH), an antioxidant, to reduce lipid peroxides generated by reactive oxygen species (ROS).* However, when lipid peroxides accumulate due to GPX4 disruption or GSH depletion, ferroptosis is triggered

Consistent with this, endothelial-specific Zip14 KO mice exhibited impaired brain Mn efflux after nasal Mn supplementation and accumulated more Mn in the brain after Mn overexposure (Maiuolo et al., 2018)

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