Figure 6.

Blockade of RIP1 or RIP3 protects against APAP injury. (a) WT and RIP3^−/− mice were treated with APAP (500 μg/g). Hematoxylin–eosin (H&E)-stained sections of the liver harvested 12 h after injury are shown, and the fraction of non-viable liver was quantified (n=10/group) (scale bar=500 μm). (b) WT and RIP3^−/− mice were also administered a potentially lethal dose of APAP (700 μg/g) and observed in a survival experiment (n=6–10/group; P=0.0001). (c–e) WT mice were treated with APAP (500 μg/g) or APAP+Nec-1 (c) H&E-stained sections of the liver harvested 12 h after injury are shown, and the fraction of non-viable liver area was quantified (n=10/group) (scale bar=500 μm). (d) Serum levels of ALT and (e) aspartate aminotransferase (AST) were determined at serial time points after injury. (f) Similarly, WT mice were administered a potentially lethal dose of APAP (700 μg/g) or APAP+Nec-1 and observed in a survival experiment (n=10/group; P<0.0001). (g) TUNEL (terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling) staining was quantified in the APAP (500 μg/g) and APAP+Nec-1 liver at various time points after injury (*P<0.05, **P<0.01, ***P<0.001). (h) Western blotting was performed for the indicated proteins using the livers of mice treated with PBS, Nec-1, APAP (500 μg/g), or APAP +Nec-1