Figure 7.
Panel (a) NCX-1000 but not UDCA inhibits cleavage of procaspase-3 and -9 and PARP in APAP-treated hepatocytes. Hepatocytes were treated with APAP (6.6 mM) with or without 50 μM NCX-1000 and UDCA for 6 h and subsequently lysed. Lane 1: control. Lane 2: APAP 6.6 μM alone. Lane 3, APAP plus 50 μM NCX-1000. Lane 4, APAP plus 40 μM UDCA. Each blot is representative of at least three others. Panel (b) NCX-1000 inhibits caspase-3 and -9 activity induced by APAP. Data are mean±s.e. of six experiments. *P<0.05 versus control; **P>0.05 versus APAP. Panel (c) Hb reverses the protective effects exerted by NCX-1000 on apoptosis and caspase-3 activation in hepatocytes challenged with 6.6 mM APAP. Cells were incubated for 6 h with APAP alone with 50 μM NCX-1000 alone or in combination with 10 mM Hb. At the end of incubation, hepatocytes were lysed and activity measured as described in Methods. Data are mean±s.e. of six experiments. *P<0.05 versus APAP plus NCX-1000.