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. 2021 Jun 22;15:2747–2767. doi: 10.2147/DDDT.S308973

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© 2021 Huang et al.

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Mechanism of the ferroptosis regulating effect of the antiparasitic agents. The inhibitory regulation of ferroptosis (the “brake”) is shown on the left side and the promotive regulation (the “accelerator”) is shown on the right side. DHA downregulates the PRIM2/SLC7A11 axis and further suppresses the GSH production. DHA also downregulates the GPX4 expression and releases the brake of ferroptosis. However, there is also evidence suggesting that DHA may upregulate GPX4 via upregulating the endoplasmic reticulum stress (ERS) and the HSPA5 expression. ARTs upregulate the expression of TFR, which would subsequently increase the intracellular iron level. ARTs associate with Fe²⁺ and prevent its combination with the IRP/IRE system, thus inhibit the expression level of ferritin and increase the intracellular iron level. DHA can also promote the degradation of ferritin.