The effect of DEM predepletion (dotted line) of hepatic GSH on APAP-induced (530 mg/kg; 0–5 h) apoptotic and necrotic cell death compared with saline treatment (solid line) in fed male CD-1 mice. Representative (A) Western analysis of hepatic processing of procaspase-3 (p32) to the active form (p17) and (B) agarose gel analysis of hepatic DNA laddering. The effect of GSH predepletion on APAP-induced (C) hepatic GSH depletion, (D) hepatic ATP depletion and serum levels of (E) caspase-cleaved K18 fragments (pmol/mL) and (F) serum HMGB1 content (ng/mL) was determined simultaneously 0–5 h after APAP treatment. Data are given as mean ± SD of six mice per group carried out in three independent investigations. Statistical significance was assigned relative to vehicle treated controls (*P < 0.05, **P< 0.01 and ***P< 0.005) or between DEM and saline pretreated mice (†P < 0.05) at that time point.