Open AccessTissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy
Author(s) -
Ishii Takeo,
Kumagae Tomohiro,
Wakui Hiromichi,
Urate Shingo,
Tanaka Shohei,
Abe Eriko,
Suzuki Toru,
Yamaji Takahiro,
Kinguchi Sho,
Kobayashi Ryu,
Haruhara Kotaro,
Nakamura Takashi,
Kobayashi Shuzo,
Tamura Kouichi
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13083
Subject(s) - aristolochic acid , uric acid , nephropathy , purine , kidney , nephrotoxicity , xanthine dehydrogenase , fibrosis , medicine , kidney disease , endocrinology , renal function , purine metabolism , pharmacology , chemistry , enzyme , biochemistry , xanthine oxidase , biology , genetics , diabetes mellitus
Xanthine oxidoreductase (XOR) is a critical enzyme in purine metabolism and uric acid production, and its levels are reported to increase during stress, thereby promoting organ damage. Herein, we investigated the activity of XOR in a mouse model of aristolochic acid I (AA)‐induced nephropathy, a type of nephrotoxic chronic kidney disease (CKD). A persistent decrease in renal function was observed in mice up to 4 weeks after 4 weeks of AA (2.5 mg kg −1 ) administration. Renal histology revealed an increase in tubular interstitial fibrosis over time. Although AA administration did not change XOR activity in the plasma, heart, liver, or muscle, XOR activity was persistently increased in renal tissue. Our results suggest that the renal tissue‐specific increase in XOR activity is involved in the progression of tubulo‐interstitial disorders, specifically fibrosis.