Figure 6

The Nrf2 stress response to acetaminophen requires reactive metabolite formation. Nrf2-luc mice (n = 3 per group) were administered saline or 100 mg/kg ABT, then 1 h later administered saline or 300 mg/kg APAP. (A) Overview of study design, with times of drug administration, imaging and serum ALT measurements indicated. (B) Serum ALT levels in mice treated as indicated, 24 h post-APAP administration. (C) In vivo and (D) ex vivo bioluminescence imaging of the same representative mice, 24 h post-APAP administration. See Fig. S8 for imaging data for all mice. (E) Luminescence signals from in vivo and ex vivo imaging of all mice. (F) qPCR analysis of Nrf2 target genes in the livers of mice treated as indicated, 24 h post-APAP administration. (G) Immunoblot analysis of Hmox1 protein levels in livers of mice at 24 h. (H) Densitometric analysis of Hmox1 proteins levels in G. Data represent mean + S.D. Statistical analysis was performed with (B,H) one-way ANOVA (Tukey’s multiple comparison) or (E,F) a Kruskal-Wallis (Conover-Inman pairwise comparison) test; *P ≤ 0.05, **P ≤ 0.001, ***P ≤ 0.001 versus saline + saline or as indicated; NS, non-significant.