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Possibly due to the ability of GPx-4 to reduce these membrane-associated hydroperoxides, it is the only subtype of mammalian GPxs for which the knockout is lethal (320), but the precise cause of the midgestational lethality caused by GPx-4 deficiency (401) is unknown, and may be unrelated to the reduction of phospholipid hydroperoxides by GPx-4

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TB-500 shares a similarly clean safety profile, though theoretical concerns exist regarding its pro-angiogenic and cell-migration properties in the context of existing tumors — direct tumorigenic evidence is lacking, but researchers working with tumor models should note the potential interaction