Figure 8.

Epoxyeicosatrienoic acid (EET) administration or pharmacological or genetic inhibition of soluble epoxide hydrolase (sEH) mitigates unilateral ureteral obstruction (UUO)-induced oxidative stress. 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 (E; 15 µg/kg/day, using an osmotic pump) for 7 days. Kidneys were harvested at 7 days after the operation. A–C: for the pharmacological inhibition of soluble epoxide hydrolase, t-TUCB (T; 0.4 mg/mouse/day) or vehicle (V) was administered by oral gavage beginning 24 h before UUO. A and B: the 4-hydroxynonenal (4-HNE) level was evaluated by Western blot analysis using anti-4-HNE antibody. GAPDH was used as a loading control. Band density was measured using ImageJ software. C: lipid peroxidation as indicated by the lipid hydroperoxide level in kidneys using a lipid hydroperoxide assay kit. 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. D and E: the 4-HNE level was evaluated by Western blot analysis using anti-4-HNE antibody. F: lipid peroxidation as indicated by the lipid hydroperoxide level in kidneys. Data are presented as means ± SD; n = 4–6. *P < 0.05; **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. TUCB, 4-[[trans-4-[[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]amino]cyclohexyl]oxy]benzoic acid.