HGA-induced apoptosis of hepatocytes in the Fah−/− Hpd−/− mice and in vivo protective effect of caspase inhibitors. The liver sections were obtained from variously treated mice and investigated as described in the text. The controls were untreated III (a), III treated with HGA (b), and untreated Fah−/− Hpd−/− (c). The positive signals of in situ detection of DNA fragmentation were seen in 30–80% of hepatocytes in the sections from Fah−/− Hpd−/− mice treated with HGA (800 mg/kg body weight) (d), 2–4% of YVAD-pretreated Fah−/− Hpd−/− treated with HGA (e), and below 1% in DEVD-pretreated Fah−/− Hpd−/− treated with HGA (f), compared with below 1% of the controls (a, III without HGA; b, III with HGA; c, Fah−/− Hpd−/− without HGA.). (Original magnification, ×400.)