Fig. 5.

PD-81723 reduces kidney necrosis (A and B), apoptosis (C), neutrophil infiltration (D), and proinflammatory gene expression (E) in A₁WT mice after renal I/R. A, C, and D: representative photomicrographs for hematoxylin and eosin (H&E) staining (A; magnification: ×200), TUNEL staining (representing apoptotic nuclei; C; magnification: ×200), and immunohistochemistry for neutrophil infiltration (D; magnification: ×400) of kidney sections of mice. Mice were pretreated with vehicle (1% DMSO) or with 3 mg/kg PD-81723 and subjected to 30 min of renal ischemia and 24 h of reperfusion. Photographs are representative of 4–5 independent experiments. B: summary of Jablonski scale renal injury scores (graded from H&E staining, scale: 0–4) for mice subjected to renal I/R. Vehicle-treated mice showed severe renal tubular necrosis, apoptosis, and neutrophil infiltration after I/R. Preischemic PD-81723 treatment significantly attenuated renal I/R injury in A₁WT mice but did not protect A₁KO mice. Values are means ± SE. #P < 0.05 vs. vehicle-treated A₁WT mice subjected to renal I/R. E: representative gel images (top) of RT-PCR and densitometric quantification of relative band intensities normalized to GAPDH (bottom) of proinflammatory markers [ICAM-1, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-2, and TNF-α] from renal cortices of A₁WT mouse kidneys (n = 4–5 mice/group). Mice were treated with vehicle or with PD-81723 (3 mg/kg) and subjected to sham operation or to renal I/R (6 h of reperfusion). PD-81723 selectively reduced expression of TNF-α and MCP-1 without affecting MIP-2 or ICAM-1 expression. Values are means ± SE. *P < 0.05 vs. the vehicle-treated sham-operated group; #P < 0.05 vs. the vehicle-treat I/R group. Data were analyzed with one-way ANOVA plus a Tukey post hoc multiple-comparison test.