Figure 3

Histological analysis of the hepatic stress response to acetaminophen in Nrf2-luc mice. Nrf2-luc mice were administered saline or 300 mg/kg APAP. At 24 h, in saline-treated mice 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 APAP-treated mice, there was extensive centrilobular coagulative necrosis with hydropic degeneration of surrounding hepatocytes (HE stain). Hmox1 was expressed by the necrotic centrilobular hepatocytes as well as individual intact hepatocytes adjacent to the affected area (arrow), whilst Kupffer cells close to affected areas also exhibited strong Hmox1 expression. Luciferase was expressed by the necrotic and degenerate centrilobular hepatocytes. CV: central vein; P: portal vein. Scale bars = 20 µm.