Fenofibrate induces apoptotic injury in cultured human hepatocytes by inhibiting phosphorylation of Akt.

摘要: Fibric acid derivatives have a potent and effective lipid-lowering action, however, the use of these compounds is sometimes limited due to occurrence hepatic injury. In present study, we characterized cell injury induced by fenofibrate in cultured human hepatocytes. Fenofibrate caused loss viability nuclear damage as assessed terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling or DNA electrophoresis, which caspase activation involved. The was accompanied shrinkage translocation phosphatidyl serine from inner membrane outer determined annexin V stain. mRNA expression for bcl-2 reduced fenofibrate. An immunofluorescent stain with antiserum raised against phosphorylated Akt revealed that inhibited insulin-stimulated phosphorylation Akt. Like fenofibrate, several inhibit Akt, including wortmannin, SH-6 high concentration (100 microM) SB203580, Both were reversed insulin concentration-dependent manner. contrast, bezafibrate 8(S)-hydroxyeicosatetraenoic had no hepatotoxic action. These findings suggest causes caspase-dependent apoptosis hepatocytes inhibiting PPARalpha not