FIGURE 7.

Inhibition of Erk1/2 signaling diminished CNI-mediated nephrotoxicity in mice. (A) Therapeutic administration of Erk1/2 inhibitor (PD 2.5 mg/kg; i.p.) in mice subjected to CsA (60 mg/kg; i.p.) or TAC (1 mg/kg; i.p.), each day for 2 weeks. (B) Kidney PAS staining showing a reduced kidney injury in mice treated with Erk1/2 inhibitor combined with CsA or TAC. Vacuolized tubules [v], tubular atrophy areas [a], and tubular dilatation [h] are indicated. (C) Tubular injury score (%) and serum creatinine in indicated groups of mice. Box and whiskers plot (min/max), n = 5 mice/group for morphometric analysis using 5 images/mouse, or n = 5 mice/group for serum creatinine, *p < .05 (ANOVA). (D) HMGB1 and nuclei fluorescence patterns in kidney sections from indicated groups of mice. Dashed boxes indicate regions that are magnified and displayed in lower panels. Arrows depict HMGB1 nucleus-to-cytosol translocation in kidney epithelial cells. (E, F) HMGB1 levels in urine from control (vehicle) mice or subjected to CsA, TAC, and PD alone, as well as CsA or TAC combined treatment with PD. Western blots and optical densitometry are shown. Data presented as box and whiskers plot (min/max), n = 5, *p < .05 (ANOVA)