The aim of this study is to reveal the effect of a xanthine oxidoreductase inhibitor, Topiroxostat (Top), compared to another inhibitor, Febuxostat (Feb), in an adenine-induced renal injury model. We used Human L-FABP chromosomal transgenic (Tg) mice and urinary liver type fatty acid binding protein (L-FABP), a biomarker of tubulointerstitial damage, were used to evaluate tubulointerstitial damage. Male Tg mice (n=24) were fed a 0.2% w/w adenine-containing diet. Two weeks after starting this diet, renal dysfunction was confirmed and the mice were divided into four groups: the adenine group was given only the diet containing adenine. The Febuxostat (Feb) group and Topiroxostat-high (Top-H) or low (Top-L) groups were given diets containing Feb (3mg/kg), Top-H (3mg/kg), and Top-L (1mg/kg) in addition to adenine for another 2 weeks. After withdrawing the adenine diet, each medication was continued for 2 weeks. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels and renal xanthine oxidoreductase (XOR) activity were significantly attenuated in the kidneys of the Feb, Top-L and Top-H groups compared to the adenine group. The serum creatinine levels in the Top-L and Top-H groups, and the renal xanthine oxidoreductase activity (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, Topiroxostat attenuated the renal damage in an adenine-induced renal injury model.
- Xanthine oxidoreductase
- Xanthine oxidoreductase inhibitor
- Copyright © 2015, American Journal of Physiology - Renal Physiology