FIG. 6.
Oxidative stress mediates NIK‐induced liver injury. (A‐D) HepNIK male mice were pretreated with NAC (300 mg/kg body weight) or empty vehicles (Con) and treated with APAP (200 mg/kg) for 24 hours. (A) Plasma ALT levels (n = 4 per group). (B) Liver ROS levels (normalized to liver weight, n = 4 per group). (C) Liver sections were stained with the indicated agents. Necrosis area, TUNEL+, MPO+, and nitrotyrosine cells were normalized to total area (n = 3‐4 mice per group). Scale bar, 200 μm. (D) Liver gene expression (normalized to 36B4 levels, n = 4 per group). (E) Mouse primary hepatocyte cultures were transduced with NIK or β‐gal adenoviral vectors, pretreated with 500 μM NAC, and followed by 2.5 mM APAP stimulation for 24 hours. Hepatocyte death was assessed by TUNEL assays (normalized to total cells, n = 3 per group). Data are presented as mean ± SEM. *P < 0.05; (B‐D) two‐tailed unpaired Student t test; (A,E) two‐way ANOVA/Bonferroni’s multiple comparisons test). Abbreviation: NitroTyr, nitrotyrosine.