Fig. 5.

FXR activation mitigates cisplatin-induced renal injury and ferroptotic response in a mouse model of cisplatin-induced AKI.

WT mice were administered with GW4064 or vehicle (soybean oil) by oral gavage (single daily administration for 4 days) as shown in the experimental outline (A). The mice were injected with cisplatin (20 mg/kg) on the third day of GW4064 administration. After 48 h of cisplatin injection, the serum and the kidneys were collected. (B) BUN, sCr, and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured in the serum. MDA, iron levels, and GSH/GSSG ratio were measured in the kidney tissue (n = 6–7). (C) Protein levels of GPX4, HMOX1, ACSL4, and FTH1 were detected by immunoblotting. The relative protein levels are shown. The values for the control group were set to 1 (n = 4). (D) The mRNA levels of the indicated genes were measured by qRT-PCR. The values for control group are set to 1. (E) Representative images of H&E and PAS staining to examine histology. Paraffin-embedded kidney tissue sections were stained with antibodies against 3-NT and 4-HNE (scale bar 100 μm). Computer-based morphometric analysis is shown (right bar graph, n = 8 in each group). All values are presented as the mean ± SD. Statistical significance was measured using one-way ANOVA with Bonferroni post hoc-test. *P < 0.05, **P < 0.005.