title: 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.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan; a2kamijo@marianna-u.ac.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kamijo-Ikemori
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; CMIC Holdings Company, Limited, Tokyo, Japan; and.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.affiliation: Biopharmaceutical Study Group, Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Company, Limited, Mie, Japan;
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hibi
authors.affiliation: Biopharmaceutical Study Group, Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Company, Limited, Mie, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Radioisotope and Chemical Analysis Center, Laboratory Management Department, Sanwa Kagaku Kenkyusho Company, Limited, Mie, Japan;
authors.forename: Takayo
authors.initials: T
authors.lastname: Murase
authors.affiliation: CMIC Holdings Company, Limited, Tokyo, Japan; and.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oikawa
authors.affiliation: Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan;
authors.forename: Seiko
authors.initials: S
authors.lastname: Hoshino
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan;
authors.forename: Mikako
authors.identifier: 0000-0002-4504-9639
authors.initials: M
authors.lastname: Hisamichi
authors.affiliation: Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan;
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Hirata
authors.affiliation: JCHO Tokyo Takanawa Hospital, Tokyo, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan;
authors.forename: Yugo
authors.initials: Y
authors.lastname: Shibagaki
mesh_terms: D000225:Adenine; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D000069465:Febuxostat / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors*
chemical_list: D015415:Biomarkers; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009570:Nitriles; D011725:Pyridines; C504882:FYX-051; D000069465:Febuxostat; D014968:Xanthine Dehydrogenase; D000225:Adenine
keywords: adenine; liver-type fatty acid-binding protein; topiroxostat; tubulointerstitial damage; xanthine oxidoreductase; xanthine oxidoreductase inhibitor