Research Article
Inhibition of Xanthine Oxidase Protects against Sepsis-Induced Acute Kidney Injury by Ameliorating Renal Hypoxia
Figure 2
Febuxostat relieves serum and renal tissue XO activity, and XO knockdown attenuates kidney injury in SI-AKI mice. (a, b) The XO activity in serum and renal tissue homogenates was measured 24 h after LPS injection. XO could oxidize xanthine and produce O2●¯, which could react with WST-8, and the color of the reaction products could be detected with a micro reader at 450 nm. (c, d) Changes in XO expression in the kidneys of SI-AKI mice were detected by immunofluorescence assay (400x magnification). (e) Timeline of AAV injection displayed. (f–i) Knockdown of XO expression was confirmed using western blot and immunofluorescence assays. (j, k) Serum and renal XO activity were evaluated. (l, m) BUN and Scr were analyzed after downregulation of XO and challenge with LPS (10 mg/kg). (n, o) Representative images of kidney tissue are presented, and the injury score was graded in a double-blinded manner. , , and vs. Ctrl; #, ##, and ### vs. LPS+Veh or LPS+Ctrl-shR (). Ctrl: control; Veh: vehicle; LPS: lipopolysaccharide; Feb: febuxostat; XO: xanthine oxidase; BUN: blood urea nitrogen; Scr: serum creatinine.
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