Disruption of xanthine oxidoreductase gene attenuates renal ischemia reperfusion injury in mice

Yoshie Haga, Toshio Ohtsubo, Noboru Murakami, Hideko Noguchi, Yasuo Kansui, Kenichi Goto, Kiyoshi Matsumura, Takanari Kitazono

Research output: Contribution to journalArticle

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Abstract

Aims We examined the roles of xanthine oxidoreductase (XOR) in renal ischemia reperfusion (IR) injury. Main methods XOR +/+ and XOR +/− mice were subjected to 24-h reperfusion after a 45-min bilateral renal artery occlusion or sham operation. We evaluated the renal damage based on the concentrations of blood urea nitrogen (BUN) and serum creatinine (Cr), and histological changes were detected by PAS staining. Xanthine dehydrogenase, oxidase (XO) and XOR activities, amounts of blood and urine 8-OHdG, and expressions of TNF-α and MCP-1 mRNA were examined. F4/80 and nitrotyrosine-positive cells were assessed by immunohistochemical staining. Key findings The BUN and Cr concentrations in the XOR +/+IR mice were increased significantly compared to those in XOR +/−IR and allopurinol-treated XOR +/+IR mice. XO and XOR activity, which were increased in IR mice, were reduced in the allopurinol-treated XOR +/+IR and XOR +/−IR mice compared to the XOR +/+IR mice. The concentrations of blood and urine 8-OHdG, and the expressions of MCP-1 and TNF-α mRNA were increased significantly in the XOR +/+IR mice compared to those in the XOR +/−IR mice. The histological analysis revealed that the XOR +/−IR and allopurinol-treated XOR +/+IR mice showed less tubular injury than the XOR +/+IR mice in the cortex regions, with the reduction of inflammation and oxidative stress assessed by the immunohistological staining for F4/80 and nitrotyrosine. Significance Both the disruption of XOR gene in XOR +/− mice and the reduction of XOR activity in allopurinol-treated XOR +/+IR mice attenuated renal tissue injury in this IR model. Reduced XOR activity during renal IR could be a beneficial treatment target.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalLife Sciences
Volume182
DOIs
Publication statusPublished - Aug 1 2017

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Xanthine Dehydrogenase
Reperfusion Injury
Genes
Kidney
Reperfusion
Ischemia
Allopurinol
Blood
Xanthine Oxidase
Blood Urea Nitrogen
Staining and Labeling
Urea
Creatinine

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Disruption of xanthine oxidoreductase gene attenuates renal ischemia reperfusion injury in mice. / Haga, Yoshie; Ohtsubo, Toshio; Murakami, Noboru; Noguchi, Hideko; Kansui, Yasuo; Goto, Kenichi; Matsumura, Kiyoshi; Kitazono, Takanari.

In: Life Sciences, Vol. 182, 01.08.2017, p. 73-79.

Research output: Contribution to journalArticle

Haga, Yoshie ; Ohtsubo, Toshio ; Murakami, Noboru ; Noguchi, Hideko ; Kansui, Yasuo ; Goto, Kenichi ; Matsumura, Kiyoshi ; Kitazono, Takanari. / Disruption of xanthine oxidoreductase gene attenuates renal ischemia reperfusion injury in mice. In: Life Sciences. 2017 ; Vol. 182. pp. 73-79.
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abstract = "Aims We examined the roles of xanthine oxidoreductase (XOR) in renal ischemia reperfusion (IR) injury. Main methods XOR +/+ and XOR +/− mice were subjected to 24-h reperfusion after a 45-min bilateral renal artery occlusion or sham operation. We evaluated the renal damage based on the concentrations of blood urea nitrogen (BUN) and serum creatinine (Cr), and histological changes were detected by PAS staining. Xanthine dehydrogenase, oxidase (XO) and XOR activities, amounts of blood and urine 8-OHdG, and expressions of TNF-α and MCP-1 mRNA were examined. F4/80 and nitrotyrosine-positive cells were assessed by immunohistochemical staining. Key findings The BUN and Cr concentrations in the XOR +/+IR mice were increased significantly compared to those in XOR +/−IR and allopurinol-treated XOR +/+IR mice. XO and XOR activity, which were increased in IR mice, were reduced in the allopurinol-treated XOR +/+IR and XOR +/−IR mice compared to the XOR +/+IR mice. The concentrations of blood and urine 8-OHdG, and the expressions of MCP-1 and TNF-α mRNA were increased significantly in the XOR +/+IR mice compared to those in the XOR +/−IR mice. The histological analysis revealed that the XOR +/−IR and allopurinol-treated XOR +/+IR mice showed less tubular injury than the XOR +/+IR mice in the cortex regions, with the reduction of inflammation and oxidative stress assessed by the immunohistological staining for F4/80 and nitrotyrosine. Significance Both the disruption of XOR gene in XOR +/− mice and the reduction of XOR activity in allopurinol-treated XOR +/+IR mice attenuated renal tissue injury in this IR model. Reduced XOR activity during renal IR could be a beneficial treatment target.",
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AU - Haga, Yoshie

AU - Ohtsubo, Toshio

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AU - Noguchi, Hideko

AU - Kansui, Yasuo

AU - Goto, Kenichi

AU - Matsumura, Kiyoshi

AU - Kitazono, Takanari

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AB - Aims We examined the roles of xanthine oxidoreductase (XOR) in renal ischemia reperfusion (IR) injury. Main methods XOR +/+ and XOR +/− mice were subjected to 24-h reperfusion after a 45-min bilateral renal artery occlusion or sham operation. We evaluated the renal damage based on the concentrations of blood urea nitrogen (BUN) and serum creatinine (Cr), and histological changes were detected by PAS staining. Xanthine dehydrogenase, oxidase (XO) and XOR activities, amounts of blood and urine 8-OHdG, and expressions of TNF-α and MCP-1 mRNA were examined. F4/80 and nitrotyrosine-positive cells were assessed by immunohistochemical staining. Key findings The BUN and Cr concentrations in the XOR +/+IR mice were increased significantly compared to those in XOR +/−IR and allopurinol-treated XOR +/+IR mice. XO and XOR activity, which were increased in IR mice, were reduced in the allopurinol-treated XOR +/+IR and XOR +/−IR mice compared to the XOR +/+IR mice. The concentrations of blood and urine 8-OHdG, and the expressions of MCP-1 and TNF-α mRNA were increased significantly in the XOR +/+IR mice compared to those in the XOR +/−IR mice. The histological analysis revealed that the XOR +/−IR and allopurinol-treated XOR +/+IR mice showed less tubular injury than the XOR +/+IR mice in the cortex regions, with the reduction of inflammation and oxidative stress assessed by the immunohistological staining for F4/80 and nitrotyrosine. Significance Both the disruption of XOR gene in XOR +/− mice and the reduction of XOR activity in allopurinol-treated XOR +/+IR mice attenuated renal tissue injury in this IR model. Reduced XOR activity during renal IR could be a beneficial treatment target.

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