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.