Figure 7.

Epoxyeicosatrienoic acid (EET) administration or pharmacological or genetic inhibition of soluble epoxide hydrolase suppresses tubular cell damages and cell death during unilateral ureteral obstruction (UUO). Male C57BL/6 mice were subjected to either UUO or sham operation and then administered with the combination of 11,12-EET + 14,15-EET (15 µg/kg/day, using an osmotic pump) for 7 days. The kidneys were harvested at 7 days after the operation. A and B: for the pharmacological inhibition of soluble epoxide hydrolase, t-TUCB (0.4 mg/mouse/day) or vehicle (Veh) was administered by oral gavage beginning 24 h before UUO. A: kidney damage was evaluated by periodic acid-Schiff (PAS) staining and damage scoring. B: kidney sections were stained using a TUNEL assay kit and aquaporin-1 (AQP1) antibody (red). TUNEL-positive cells (green) were counted by microscopy. C and D: Ephx2^+/+ and Ephx2^–/– mice were subjected to either UUO or sham operation and then administered with the combination of 11,12-EET + 14,15-EET. C: kidney damage was evaluated by PAS staining and damage scoring. D: kidney sections were stained using a TUNEL assay kit and AQP1 antibody (red). Hematoxylin and DAPI stain (both blue) were used for counterstaining. Pictures of the cortex were taken. Scale bars = 50 μm. Data are presented as means ± SD; n = 6. **P < 0.01; ***P < 0.001; ****P < 0.0001. One-way or two-way ANOVA followed by a Tukey’s post hoc multiple comparison test was used to determine significance. t-TUCB, 4-[[trans-4-[[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]amino]cyclohexyl]oxy]benzoic acid.