Figure 3.

PD146176, a specific 15-lipoxygenase (LO) inhibitor, effectively blunts 15-LO eicosanoid production and reverses renal fibrosis after unilateral ureteral obstruction (UUO). A: C57BL/6 wild-type (WT) vehicle (veh)-treated and PD146176-treated UUO-injured kidneys and controls (Ctrl) underwent histological staining for picrosirius red (PSR) and F4/80 immunohistochemistry (IHC). Representative ×20 images are shown. B: corresponding quantification of PSR-polarized images and F4/80 immunostained images. Also shown is the hydroxyproline assessment for fibrosis (normalized to mg total protein) and percent weight changes from baseline between the two groups. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 by one-way ANOVA. C: WT and PD146176-treated kidneys were analyzed by LC-MS/MS for 15-LO and 5-LO-derived oxylipins. Data were quantified as pg/mL of homogenized tissue. Plots are means ± SE. *P < 0.05 and **P < 0.01 by one-way ANOVA. HETE, hydroxyeicosatetraenoic acid; HODE, hydroxyeicosaoctadecaenoic acid; ns, not significant.