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16 BrkicS.TomicS.MaricD.Novakov MikicA.TurkulovV

Under oxidative stress and induced by excessive ROS generation, Nrf2 is released from its inhibitor Keap1, allowing its translocation into the nucleus (Kasprzak et al., 2020), where it binds to the antioxidant response element (ARE) present in the DNA sequence of numerous antioxidant enzymes like glutathione-S-transferase, -glutamyl cysteine synthetase (glutamate cysteine ligase), heme oxygenase 1, and paraoxonase-1 inducing their transcription, managing the phase II response to oxidative stress (Kasprzak et al., 2020)

Study limitations Several limitations should be acknowledged

Pifithrin- induces necroptosis through oxidative mitochondrial damage but accompanies epithelialmesenchymal transition-like phenomenon in malignant mesothelioma cells under lactic acidosis