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The importance of zinc homeostasis is highlighted by the remarkable number of diseases associated with alterations in tissue zinc levels, which is summarized in Figure 1 (right hand side)

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359 Shikonins dual inhibition of TRXR and PKM2 induces necroptosis, whereas Nrf2 hyperactivation mediates resistance, which can be reversed through metabolic targeting

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Therefore, the GPx-like catalytic activity of compounds was studied using glutathione (GSH) as thiol cofactor and hydrogen peroxide (H 2 O 2 ) as substrate [57, 58]

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No tolerance developed to this protective effect, which appeared to be mediated by (1) the activation of 5-HT 1A receptors, as it was antagonized by the administration of WAY100635 30 min before stress exposure

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