The JNK inhibitor, SP600125, blocks down‐regulation of ARE‐driven genes induced by APAP in mouse liver. SP600125 (10 mg/kg IP) was given to WT and Nrf2−/− mice 1 hour before injection of APAP (300 mg/kg IP). Livers were harvested 6 and 24 hours after administration of APAP. (A) Serum ALT levels at 6 hours (n = 3‐6). (B) Hematoxylin and eosin staining of liver sections at 6 hours (original magnification, ×200; scale bars, 50 μm; P, portal venules; C, central venules). g, the percentage of necrotic area by semiquantification (mean ± SD; n = 3‐5). (C) SP600125 blocked the decrease of Nqo1, AKR1C, Gstα3, Gstm1, and Gstm5 expression in APAP‐treated liver. Protein extracts were prepared from livers of WT mice harvested at 6 and 24 hours after administration of APAP. Western immunoblottings were probed with the indicated antibodies. Each lane contains a sample from a single mouse. Lower panel, semiquantitative results of blottings. The value from the WT group treated with vehicle was set at 1. Values are mean ± SD (n = 3). *P < 0.05; **P < 0.01 versus WT vehicle. ##
P < 0.01 versus WT treated with SP600125 and APAP at 24 hours.