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...
Main Authors: | , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Wiley
2021-02-01
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Series: | FEBS Open Bio |
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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. |
first_indexed | 2024-04-13T06:37:08Z |
format | Article |
id | doaj.art-1b23ed7e3f21462fbfde4df342814d61 |
institution | Directory Open Access Journal |
issn | 2211-5463 |
language | English |
last_indexed | 2024-04-13T06:37:08Z |
publishDate | 2021-02-01 |
publisher | Wiley |
record_format | Article |
series | FEBS Open Bio |
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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