Fig. 6.

FXR deficiency exacerbates cisplatin-induced renal injury and ferroptotic response in a mouse model of the AKI.

The WT and FXR knockout mice were intraperitoneally injected with cisplatin (20 mg/kg) or vehicle control (saline). After 48 h of cisplatin injection, the serum and the kidneys were collected. (A) BUN, sCr, and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured in the serum. MDA and iron levels and GSH/GSSG ratio were measured in the kidney tissue (n = 6–7). (B) Protein levels of GPX4, HMOX1, ACSL4, and FTH1 were detected by immunoblotting. The relative protein levels are shown. The values for the WT control group were set to 1 (n = 4). (C) The mRNA levels of the indicated genes were measured by qRT-PCR. The values for the control group are set to 1. (D) 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 = 7–8 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.