Figure 4.

Inhibition of cathepsin is protective in in vivo models known to be driven via the HMGB1-TLR4 axis (A,B) Survival curves of male BALB/c mice that underwent cecal ligation and puncture (CLP). SQV or 334 was administered at 0.5 mg (SQV) or 5 mg (334) per mouse (IP in 200 μL PBS-DMSO) per day for 3 d starting at 24 h after CLP surgery. Control mice in received vehicle (PBS-DMSO) only. Animal survival was monitored for up to 2 wks. N = 20 mice per group. *P < 0.05 versus control group. (C-D) C57BL6/J mice underwent 70% warm liver ischemia for 1 h followed by reperfusion for 6 h. Mice were treated with SQV or vehicle 1 h prior to ischemia and again at the time of reperfusion. SQV attenuated liver I/R injury as measured by (C) plasma ALT levels and (D) histological examination of H&E-stained liver sections with indicated percent necrosis quantitated in each image.