3.2 Nrf2 KO mice are susceptible to cisplatin-induced lipid peroxidation and ferroptosis
Nrf2 is a key reliever of lipid peroxidation and ferroptosis, and abnormal Nrf2 signaling is thought to aggravate the disease by regulating lipid peroxides and ferroptosis. We investigated lipid peroxidation and ferroptosis in Nrf2 KO mice and found that their malondialdehyde (MDA) levels were increased to a greater extent than those in the WT mice, while the GSH levels were significantly decreased in Nrf2 KO mice after cisplatin injection compared to those in the WT mice (Fig. 2A-B). We further examined the protein expression of GPX4 and xCT, biomarkers of ferroptosis, to clarify the role of Nrf2 in ferroptosis. As shown in Fig. 2C-F, both the mRNA and protein levels of GPX4 and xCT were significantly decreased in Nrf2 KO mice compared with WT mice.