キムラ ケンジロウ   KIMURA KENJIRO
  木村健二郎
   所属   医学部医学科 腎臓・高血圧内科
   職種   客員教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury.
掲載誌名 正式名:American journal of physiology. Renal physiology
略  称:Am J Physiol Renal Physiol
ISSNコード:03636127/15221466
巻・号・頁 310(11),F1366-1376頁
著者・共著者 Kamijo-Ikemori Atsuko, Sugaya Takeshi, Hibi Chihiro, Nakamura Takashi, Murase Takayo, Oikawa Tsuyoshi, Hoshino Seiko, Hisamichi Mikako, Hirata Kazuaki, Kimura Kenjiro, Shibagaki Yugo.
発行年月 2016/06
概要 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.

Copyright © 2016 the American Physiological Society.