Figure 6

Histological determination of the effect of fasting and Z-VAD.fmk and anti-HMGB1 coapplication on APAP-induced hepatic changes in mice, 24 h after treatment. (A) In fed mice, there is no evidence of hepatocyte necrosis and the liver looks unaltered apart from an increased number of mitotic hepatocytes (arrow). There is no evidence of inflammatory cell recruitment into the liver. (B,C) Mice fasted for 24 h before treatment (B) and mice treated with APAP + Z-VAD.fmk show evidence of marked hepatocyte loss (score 3) and exhibit neutrophils in the lumen and rolling along endothelial cells (arrows) of central and portal veins, indicating leukocyte recruitment into the liver. (D) Mouse fasted for 24 h before APAP treatment. Closer view of a central vein with numerous neutrophils rolling along endothelial cells (arrows). (E). Treatment of fasted mice with APAP and anti-HMGB1 is associated with evidence of marked hepatocyte loss (score 3), but not of inflammatory cell recruitment into the liver. (F) After treatment of fasted mice with APAP and IgY; however, evidence of marked hepatocyte loss (score 3) and evidence of leukocyte recruitment, represented by neutrophils rolling along endothelial cells (arrows) of central and portal veins, is seen. Hematoxylin and eosin stain. Bars = 20 µm. PA, portal area; CV, central vein. Figures are representative of six animals per group carried out in three independent investigations.