Figure 2

Atorvastatin does not induce hepatocyte caspases. Panel A, untreated liver specimens from TO mice. Panel B, atorvastatin-treated liver specimens from TO mice. Panel C, untreated liver specimens from C57Bl/6 mice. Panel D, atorvastatin-treated liver specimens from C57Bl/6 mice. Representative experiments of liver specimens incubated in vitro at 37°C with (B and D) and without (A and C) 1.0 μM atorvastatin for 6 hr are shown. At the end of incubation period, the samples (24.7 to 35.1 mg) were rinsed and incubated at 37°C in 1.0 mL oxygenated KH buffer with and without 32 μ M zVAD-fmk for 10 min. Ac-DEVD-AMC (37 μ M) was then added and the incubation continued for 20 min. The tissues were vigorously disrupted and the supernatants were separated on HPLC and analyzed for the AMC (R _t , ~5.0 min) and Ac-DEVD-AMC peaks (R _t , ~2.5 min). Eleven independent experiments were done with the TO mice and 4 independent experiments were done with the C57Bl/6 mice.