APAP-induced liver injury in WT and PAR-4^−/− mice. PAR-4^−/− mice and matching WT mice were treated with 300 mg/kg APAP IP. (A) Quantification of CD41 signal in the liver at 2 hours. Signal intensity of CD41 was normalized to that of WT mice not treated with APAP. (B) TAT concentration in plasma at 2 hours after APAP injection. (C) ALT activity in plasma. (D) Area of necrosis and degeneration in the liver. (E) RBC to total liver tissue (%). (F) Nitrotyrosine label quantified in liver sections as described in “Materials and methods” at 6 hours after APAP injection. (G) Plasma hyaluronic acid was determined 24 hours after APAP administration (n = 6-7 mice per group). ^&Significantly different from all the other groups. *Significantly different from the WT group at same time. ^#Significantly different from APAP-treated WT mice. For WT mice, the number of mice per group was 4 (0 hour), 13 (2 hours), 10 (6 hours), and 13 (24 hours). For PAR-4^−/− mice, the number of mice per group was 3 (0 hour), 10 (2 hours), 9 (6 hours), and 14 (24 hours).