Figure 7

Histological analysis of the effect of aminobenzotriazole on the hepatic stress response to acetaminophen in Nrf2-luc mice. Nrf2-luc mice were administered saline or 100 mg/kg ABT, then 1 h later administered saline or 300 mg/kg APAP. At 24 h, in mice treated with saline + saline, there were no histological changes (HE stain), Hmox1 expression was restricted to Kupffer cells and erythrocytes within sinuses, and staining for luciferase yielded only a non-specific serum reaction. In mice treated with saline + APAP, there was extensive centrilobular coagulative necrosis with glycogen loss (confirmed by PAS reaction, data not shown) of surrounding hepatocytes (HE stain). Hmox1 was expressed by the necrotic centrilobular hepatocytes as well as proximate Kupffer cells. Luciferase was expressed by the necrotic and degenerate centrilobular hepatocytes. The livers of mice treated with ABT + saline showed features identical to those observed in mice treated with saline + saline (see above). In mice treated with ABT + APAP, histological changes (HE stain) were restricted to a slight condensation of centrilobular hepatocytes (equivalent of reduced glycogen content; PAS reaction not shown). Hmox1 expression was seen in random individual and occasional smaller aggregates of morphologically unaltered hepatocytes (arrows). Kupffer cells close to positive hepatocytes also showed enhanced expression of Hmox1 (small arrows). Luciferase expression was detected in random individual and occasional smaller aggregates of morphologically unaltered hepatocytes (arrows). CV: central vein; P: portal vein. Scale bars = 20 µm.