In Vivo Imaging of the Intra-and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging

Keiji Yasukawa, Ryota Shigemi, Tomomi Kanbe, Yusaku Mutsumoto, Fumiko Oda, Kazuhiro Ichikawa, Ken-Ichi Yamada, Xin Tun, Hideo Utsumi

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Aims: Repeated use of nonsteroidal anti-inflammatory drugs can induce changes in the redox status, including production of reactive oxygen species (ROS), but the specific details of these changes remain unknown. Overhauser-enhanced magnetic resonance imaging (OMRI) has been used in vivo to monitor the redox status in several diseases and map tissue oxygen concentrations. We monitored the intra-and extracellular redox status in the stomach of rats with indomethacin-induced gastric ulcers using OMRI and investigated the relationship with gastric mucosal damage. Results: One hour after oral administration of indomethacin (30 mg/kg), OMRI measurements in the stomach were made following nitroxyl probe administration. OMRI with the membrane-permeable nitroxyl probe, 4-hydroxy-2,2,6,6-Tetramethyl-piperidine-1-oxyl (TEMPOL), demonstrated a redox change toward oxidation, which was reversed by a membrane-permeable antioxidant. Conversely, imaging with the impermeable probe, 4-Trimethylammonium-2,2,6,6-Tetramethyl-piperidine-1-oxyl (CAT-1), demonstrated little redox change. Redox imbalance imaging of a live rat stomach with indomethacin-induced gastric ulcers was produced by dual imaging of 15 N-labeled TEMPOL and 14 N-labeled CAT-1, in addition to imaging with another membrane-permeable 15 N-labeled probe, 3-methoxycarbonyl-2,2,5,5-Tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL), and 14 N-labeled CAT-1. Pretreatment with MC-PROXYL suppressed gastric mucosal damage, whereas pretreatment with CAT-1 did not suppress ulcer formation. Innovation: OMRI combined with a dual probe is a less invasive imaging technique for evaluation of intracellular ROS production contributing to the formation of gastric ulcers in the stomach of indomethacin-Treated rats, which cannot be done with other methods. Conclusion: This method may be a very powerful tool for characterizing the pathogenesis of various diseases and may have medical applications.

元の言語英語
ページ(範囲)1147-1161
ページ数15
ジャーナルAntioxidants and Redox Signaling
30
発行部数9
DOI
出版物ステータス出版済み - 1 1 2019

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Stomach Ulcer
Indomethacin
Oxidation-Reduction
Rats
Stomach
Magnetic Resonance Imaging
Imaging techniques
Magnetic resonance
Membranes
Reactive Oxygen Species
Ulcer
Oral Administration
Anti-Inflammatory Agents
Antioxidants
Oxygen
Medical applications
Pharmaceutical Preparations
Innovation
2,2,6,6-tetramethyl-1-piperidine
Tissue

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

これを引用

In Vivo Imaging of the Intra-and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging. / Yasukawa, Keiji; Shigemi, Ryota; Kanbe, Tomomi; Mutsumoto, Yusaku; Oda, Fumiko; Ichikawa, Kazuhiro; Yamada, Ken-Ichi; Tun, Xin; Utsumi, Hideo.

:: Antioxidants and Redox Signaling, 巻 30, 番号 9, 01.01.2019, p. 1147-1161.

研究成果: ジャーナルへの寄稿記事

Yasukawa, Keiji ; Shigemi, Ryota ; Kanbe, Tomomi ; Mutsumoto, Yusaku ; Oda, Fumiko ; Ichikawa, Kazuhiro ; Yamada, Ken-Ichi ; Tun, Xin ; Utsumi, Hideo. / In Vivo Imaging of the Intra-and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging. :: Antioxidants and Redox Signaling. 2019 ; 巻 30, 番号 9. pp. 1147-1161.
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abstract = "Aims: Repeated use of nonsteroidal anti-inflammatory drugs can induce changes in the redox status, including production of reactive oxygen species (ROS), but the specific details of these changes remain unknown. Overhauser-enhanced magnetic resonance imaging (OMRI) has been used in vivo to monitor the redox status in several diseases and map tissue oxygen concentrations. We monitored the intra-and extracellular redox status in the stomach of rats with indomethacin-induced gastric ulcers using OMRI and investigated the relationship with gastric mucosal damage. Results: One hour after oral administration of indomethacin (30 mg/kg), OMRI measurements in the stomach were made following nitroxyl probe administration. OMRI with the membrane-permeable nitroxyl probe, 4-hydroxy-2,2,6,6-Tetramethyl-piperidine-1-oxyl (TEMPOL), demonstrated a redox change toward oxidation, which was reversed by a membrane-permeable antioxidant. Conversely, imaging with the impermeable probe, 4-Trimethylammonium-2,2,6,6-Tetramethyl-piperidine-1-oxyl (CAT-1), demonstrated little redox change. Redox imbalance imaging of a live rat stomach with indomethacin-induced gastric ulcers was produced by dual imaging of 15 N-labeled TEMPOL and 14 N-labeled CAT-1, in addition to imaging with another membrane-permeable 15 N-labeled probe, 3-methoxycarbonyl-2,2,5,5-Tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL), and 14 N-labeled CAT-1. Pretreatment with MC-PROXYL suppressed gastric mucosal damage, whereas pretreatment with CAT-1 did not suppress ulcer formation. Innovation: OMRI combined with a dual probe is a less invasive imaging technique for evaluation of intracellular ROS production contributing to the formation of gastric ulcers in the stomach of indomethacin-Treated rats, which cannot be done with other methods. Conclusion: This method may be a very powerful tool for characterizing the pathogenesis of various diseases and may have medical applications.",
author = "Keiji Yasukawa and Ryota Shigemi and Tomomi Kanbe and Yusaku Mutsumoto and Fumiko Oda and Kazuhiro Ichikawa and Ken-Ichi Yamada and Xin Tun and Hideo Utsumi",
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T1 - In Vivo Imaging of the Intra-and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging

AU - Yasukawa, Keiji

AU - Shigemi, Ryota

AU - Kanbe, Tomomi

AU - Mutsumoto, Yusaku

AU - Oda, Fumiko

AU - Ichikawa, Kazuhiro

AU - Yamada, Ken-Ichi

AU - Tun, Xin

AU - Utsumi, Hideo

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Aims: Repeated use of nonsteroidal anti-inflammatory drugs can induce changes in the redox status, including production of reactive oxygen species (ROS), but the specific details of these changes remain unknown. Overhauser-enhanced magnetic resonance imaging (OMRI) has been used in vivo to monitor the redox status in several diseases and map tissue oxygen concentrations. We monitored the intra-and extracellular redox status in the stomach of rats with indomethacin-induced gastric ulcers using OMRI and investigated the relationship with gastric mucosal damage. Results: One hour after oral administration of indomethacin (30 mg/kg), OMRI measurements in the stomach were made following nitroxyl probe administration. OMRI with the membrane-permeable nitroxyl probe, 4-hydroxy-2,2,6,6-Tetramethyl-piperidine-1-oxyl (TEMPOL), demonstrated a redox change toward oxidation, which was reversed by a membrane-permeable antioxidant. Conversely, imaging with the impermeable probe, 4-Trimethylammonium-2,2,6,6-Tetramethyl-piperidine-1-oxyl (CAT-1), demonstrated little redox change. Redox imbalance imaging of a live rat stomach with indomethacin-induced gastric ulcers was produced by dual imaging of 15 N-labeled TEMPOL and 14 N-labeled CAT-1, in addition to imaging with another membrane-permeable 15 N-labeled probe, 3-methoxycarbonyl-2,2,5,5-Tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL), and 14 N-labeled CAT-1. Pretreatment with MC-PROXYL suppressed gastric mucosal damage, whereas pretreatment with CAT-1 did not suppress ulcer formation. Innovation: OMRI combined with a dual probe is a less invasive imaging technique for evaluation of intracellular ROS production contributing to the formation of gastric ulcers in the stomach of indomethacin-Treated rats, which cannot be done with other methods. Conclusion: This method may be a very powerful tool for characterizing the pathogenesis of various diseases and may have medical applications.

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