FIGURE 2.

Time course of GSH depletion, JNK activation, and liver injury following APAP treatment in vivo. A, total liver homogenate GSH; B, mitochondrial GSH; C, JNK activation; D, JNK inhibitor prevents JNK activation (4 h following APAP treatment); E, early time course of serum ALT reflecting liver injury. C57BL/6 mice were treated with APAP (600 mg/kg) dissolved in warm PBS and pretreated with either JNK inhibitor (10 mg/kg in DMSO (8.3%) and PBS) or equivalent amounts of DMSO in PBS 1 h prior APAP treatment. At indicated times liver were taken, ALT measurements made in serum, GSH measured using HPLC with electrochemical detection, and Western blot analysis was performed using antisera against phospho-JNK, JNK, and actin as loading control. ♦, control; ▴, APAP; ▪, APAP plus JNK inhibitor. Results are mean ± S.D. *, p < 0.05 versus APAP treatment alone. n = 3–5 mice.