Figure 4. Broad-spectrum PKC inhibitor protects against APAP-induced liver injury in vivo through a JNK-independent pathway.
A) Effect of broad-spectrum PKC inhibitor or JNK inhibitor on serum ALT levels following APAP treatment. Mice were pre-treated with Ro-31-8452 (10 mg/kg in DMSO (8.3%) and PBS; black bars), JNK inhibitor (SP600125; 10 mg/kg in DMSO (8.3%); gray bars) or PBS with equivalent amounts of DMSO for control, 1 h prior to APAP treatment (open bars). B) H&E histology of mice treated with APAP 500 mg/kg with or without Ro-31-8425. C) Effect of Ro-31-8425 treatment on GSH levels in liver homogenate and isolated mitochondria following APAP treatment (2 h). GSH was measured using HPLC with electrochemical detection. D) Effect of Ro-31-8425 treatment on JNK activation and translocation to mitochondria following APAP treatment in vivo. PHB1 = Prohibitin1, a mitochondrial loading control. * p value ≤ 0.05 versus APAP treatment at equivalent time points or dose. N = 4–10 mice per group.