Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy

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 typ...

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Main Authors: Takeo Ishii, Tomohiro Kumagae, Hiromichi Wakui, Shingo Urate, Shohei Tanaka, Eriko Abe, Toru Suzuki, Takahiro Yamaji, Sho Kinguchi, Ryu Kobayashi, Kotaro Haruhara, Takashi Nakamura, Shuzo Kobayashi, Kouichi Tamura
Format: Article
Language:English
Published: Wiley 2021-02-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13083
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author Takeo Ishii
Tomohiro Kumagae
Hiromichi Wakui
Shingo Urate
Shohei Tanaka
Eriko Abe
Toru Suzuki
Takahiro Yamaji
Sho Kinguchi
Ryu Kobayashi
Kotaro Haruhara
Takashi Nakamura
Shuzo Kobayashi
Kouichi Tamura
author_facet Takeo Ishii
Tomohiro Kumagae
Hiromichi Wakui
Shingo Urate
Shohei Tanaka
Eriko Abe
Toru Suzuki
Takahiro Yamaji
Sho Kinguchi
Ryu Kobayashi
Kotaro Haruhara
Takashi Nakamura
Shuzo Kobayashi
Kouichi Tamura
author_sort Takeo Ishii
collection DOAJ
description 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.
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spelling doaj.art-1b23ed7e3f21462fbfde4df342814d612022-12-22T02:57:51ZengWileyFEBS Open Bio2211-54632021-02-0111250751810.1002/2211-5463.13083Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathyTakeo Ishii0Tomohiro Kumagae1Hiromichi Wakui2Shingo Urate3Shohei Tanaka4Eriko Abe5Toru Suzuki6Takahiro Yamaji7Sho Kinguchi8Ryu Kobayashi9Kotaro Haruhara10Takashi Nakamura11Shuzo Kobayashi12Kouichi Tamura13Department of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanMedical Affairs Department Sanwa Kagaku Kenkusho., Co., Ltd Aichi JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanDepartment of Medical Science and Cardiorenal Medicine Yokohama City University Graduate School of Medicine Kanagawa JapanXanthine 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.https://doi.org/10.1002/2211-5463.13083aristolochic acidmouse modelnephropathyxanthine oxidoreductase
spellingShingle Takeo Ishii
Tomohiro Kumagae
Hiromichi Wakui
Shingo Urate
Shohei Tanaka
Eriko Abe
Toru Suzuki
Takahiro Yamaji
Sho Kinguchi
Ryu Kobayashi
Kotaro Haruhara
Takashi Nakamura
Shuzo Kobayashi
Kouichi Tamura
Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy
FEBS Open Bio
aristolochic acid
mouse model
nephropathy
xanthine oxidoreductase
title Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy
title_full Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy
title_fullStr Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy
title_full_unstemmed Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy
title_short Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy
title_sort tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy
topic aristolochic acid
mouse model
nephropathy
xanthine oxidoreductase
url https://doi.org/10.1002/2211-5463.13083
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