Fig. 6

High-dose AUR induces ferroptosis and lethality in Hfe^−/− mice. a, b Body weight curve (a), serum ALT activity (b), hepatic MDA content (b) and hepatic Txnrd activity (b) was measured in male Hfe^−/− mice (n = 10 mice per group) receiving daily intraperitoneal injections of AUR (5 mg/kg) or saline (control) for 6 weeks starting at 8 weeks of age. c Kaplan–Meier survival curves of male and female Hfe^−/− mice (n = 10 mice per group) following daily intraperitoneal injections of saline (control) or AUR (25 mg/kg body weight) for 6 weeks starting at 16 weeks of age. d Huh7 cells were treated with 2.5 μM AUR and the indicated inhibitors; cell viability, lipid peroxidation, and PTGS2 mRNA were measured 12 or 24 h after treatment. e Kaplan–Meier survival curves of male and female Hfe^−/− mice (n = 10 mice per group) treated daily with AUR (25 mg/kg body weight) either with or without Fer-1 (1 mg/kg body weight); for comparison purposes only, the AUR data are reproduced from panel c. f, g Serum ALT activity (f), hepatic MDA content (f), hepatic Ptgs2 mRNA (f), and hepatic Txnrd activity (g) were measured in male Hfe^−/− mice (n = 5 mice per group) following daily intraperitoneal injections of saline (control), or AUR (25 mg/kg body weight) with or without Fer-1 (1 mg/kg body weight) for 6 weeks. The mRNA levels were normalized to β-actin and are expressed relative to the mean control value. Error bars indicate the SEM. The data in a and b were analyzed using the Student’s t-test and no significant difference was detected (N.S.). The cell line based experiments were repeated three independent times. The data in c and e were analyzed calculated using the log-rank (Mantel–Cox) test (**p < 0.01). All other summary data were analyzed using a one-way ANOVA with Tukey’s post hoc test; groups labeled without a common letter were significantly different (p < 0.05)