Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury.

Abstract

The aim of the present study was to reveal the effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.

• Authors: Atsuko Kamijo-Ikemori, Takeshi Sugaya, Chihiro Hibi, Takashi Nakamura, Takayo Murase, Tsuyoshi Oikawa, Seiko Hoshino, Mikako Hisamichi, Kazuaki Hirata, Kenjiro Kimura, Yugo Shibagaki
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 310 Issue 11 Pg. F1366-76 (06 01 2016) ISSN: 1522-1466 [Electronic] United States
• PMID: 27029427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• Biomarkers
• Fabp1 protein, mouse
• Fatty Acid-Binding Proteins
• Nitriles
• Pyridines
• FYX-051
• Febuxostat
• Xanthine Dehydrogenase
• Adenine

Topics

• Adenine
• Animals
• Biomarkers (metabolism)
• Fatty Acid-Binding Proteins (metabolism)
• Febuxostat (pharmacology, therapeutic use)
• Kidney (drug effects, metabolism, pathology)
• Kidney Diseases (chemically induced, drug therapy, pathology)
• Male
• Mice
• Mice, Transgenic
• Nitriles (pharmacology, therapeutic use)
• Pyridines (pharmacology, therapeutic use)
• Xanthine Dehydrogenase (antagonists & inhibitors)