Figure 5. Effects of the cPLA₂ inhibitor on Fas-induced hepatocyte apoptosis and liver injury in wild type mice.

The animals were injected intraperitoneally with the cPLA₂α inhibitor pyrrolidine (3 mg/kg body weight) 30 minutes before intraperitoneal administration of Jo2 (0.5 mg/kg body weight). The animals were sacrificed 4 hours after Jo2 injection and the liver tissues were harvested. (A) Representative H&E and TUNEL stains (200×) of the liver tissues from mice pretreated with or without inhibitors (all the mice received Jo2 injection). (B) Quantitation of TUNEL-positive hepatocytes in mice pretreated with or without inhibitors (*p < 0.01 compared to the corresponding wild type mice without inhibitor pretreatment, n = 6 for each group). (C) Serum transaminases. Blood samples were collected at the time of sacrifice and sera were separated for transaminase analysis. Pretreatment of wild type mice with cPLA₂ inhibitor induced significantly higher serum ALT and AST levels when compared to pretreatment with vehicle control. The data are expressed as mean ±SD from 6 mice (*p<0.01 vs. corresponding mice pretreated with vehicle, Student’s t test). (D) Caspase activities. The harvested liver tissues were homogenized for subsequent caspase activity assay. Caspase-3, 9, and 8 activities were measured by fluorometric assay with Ac-DEVD-AFC, Ac-LEHD-AFC, and Ac-IETD-AFC as substrate, respectively. Pretreatment with cPLA₂ inhibitor induced significantly higher caspase activities than the vehicle control. The results are expressed as mean ±SD of fold changes over wild type livers (*p<0.01 compared to the corresponding mice pretreated with vehicle, n = 6 for each group).