Effect of platelet depletion on APAP-induced hepatotoxicity. Mice were treated with 300 mg/kg APAP or vehicle IP at time 0 hour. Anti-CD41 antibody or isotype control antibody (2 mg/kg) was given IP 12 and 2 hours before administration of APAP. (A) Blood platelet concentration. (B) Quantification of CD41 signal in the liver at 3 hours after APAP injection. Signal intensity of CD41 from different groups was normalized to saline-pretreated group at time 0 hour. (C) Concentration of TAT complexes in plasma over time. (D) ALT activity in plasma. (E) Area of liver necrosis and degeneration. (F) RBC to total liver tissue (%). (G) Nitrotyrosine label at 6 hours at after APAP injection quantified as described in “Materials and methods.” (H) Representative liver sections from each group at 6 and 24 hours after APAP injection (×20 objective). *Significantly different from control IgG group at the same time. For mice given control IgG, the number of mice per group was 5 (0 hour), 3 (2 hours), 7 (3 hours), 13 (6 hours), and 13 (24 hours). For mice given anti-CD41 IgG, the number of mice per group was 5 (0 hour), 4 (2 hours), 7 (3 hours), 15 (6 hours), and 15 (24 hours).