<i>In Vivo</i> 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

doi:10.1089/ars.2017.7336

Cited by 12 publications

(6 citation statements)

References 51 publications

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“…Overhauser-enhanced MRI (OMRI) or proton electron double resonance imaging (PEDRI) is another magnetic resonance technique for imaging nitroxyl radicals in vivo (123,166). These techniques can produce and observe dynamic nuclear polarization (DNP) effect in vivo by injecting a nitroxyl radical compound into experimental animals (24,41,186). Nitroxyl compounds are not suitable for producing better DNP effects due to the relatively broad EPR line width, that is, fast relaxation time, even using a 15 N-labeled nitroxyl radical compound.…”

Section: Introductionmentioning

confidence: 99%

Nitroxyl Radical as a Theranostic Contrast Agent in Magnetic Resonance Redox Imaging

Matsumoto

Nakanishi

Zhelev

et al. 2022

Antioxidants & Redox Signaling

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Significance: In vivo assessment of paramagnetic and diamagnetic conversions of nitroxyl radicals based on cyclic redox mechanism can be an index of tissue redox status. The redox mechanism of nitroxyl radicals, which enables their use as a normal tissue-selective radioprotector, is seen as being attractive on planning radiation therapy. Recent Advances: In vivo redox imaging using nitroxyl radicals as redox-sensitive contrast agents has been developed to assess tissue redox status. Chemical and biological behaviors depending on chemical structures of nitroxyl radical compounds have been understood in detail. Polymer types of nitroxyl radical contrast agents and/or nitroxyl radical-labeled drugs were designed for approaching theranostics. Critical Issues: Nitroxyl radicals as magnetic resonance imaging (MRI) contrast agents have several advantages compared with those used in electron paramagnetic resonance (EPR) imaging, while support by EPR spectroscopy is important to understand information from MRI. Redox-sensitive paramagnetic contrast agents having a medicinal benefit, that is, nitroxyl-labeled drug, have been developed and proposed. Future Directions: A development of suitable nitroxyl contrast agent for translational theranostic applications with high reaction specificity and low normal tissue toxicity is under progress. Nitroxyl radicals as redoxsensitive magnetic resonance contrast agents can be a useful tool to detect an abnormal tissue redox status such as disordered oxidative stress. Antioxid. Redox Signal. 00, 000-000.

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Section: Introductionmentioning

confidence: 99%

Nitroxyl Radical as a Theranostic Contrast Agent in Magnetic Resonance Redox Imaging

Matsumoto

Nakanishi

Zhelev

et al. 2022

Antioxidants & Redox Signaling

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“…The drugs used as standards (codeine and indomethacin) were used at doses based on tests that demonstrated both efficacy for the model and safety for animals (13)(14)(15)(16)(17)(18). The doses of PA-In5 were determined according to the protocols of the Organization for Economic Co-operation and Development (protocol nos.…”

Section: Methodsmentioning

confidence: 99%

PA‑Int5: An isatin‑thiosemicarbazone derivative that exhibits anti‑nociceptive and anti‑inflammatory effects in Swiss mice

et al. 2021

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Pain and inflammation are symptoms of various diseases, and they can be modulated by different pathways, thus highlighting the importance of investigating the therapeutic effects of novel compounds. Previous studies have shown that isatin-thiosemicarbazone exhibits antitumor, antifungal antibacterial and other biological properties. Based on the wide range of biological effects of these compounds, the aim of the present study was to investigate the central nervous system (CNS) performance, and the anti-nociceptive and anti-inflammatory activity of (Z)-2-(5-nitro-2-oxoindolin-3-ilidene)-N-hydroazinecarbothioamide (PA-Int5) in treated mice. Three doses of PA-Int5 were tested orally (1.0, 2.5 and 5.0 mg/kg) in the nociceptive and inflammatory animal models. Additionally, the potential sedative effects of PA-Int5 (5 mg/kg, oral gavage) were investigated using an open ﬁeld and rotarod tests, to exclude any possible unspecific effects of the nociceptive assays. Anti-nociceptive activity was assessed using the acetic acid-induced abdominal contortion and formalin tests, whereas anti-inflammatory activity was assessed using a carrageenan-induced paw edema and zymosan-induced air-pouch models. PA-Int5 (5 mg/kg) induced anti-nociceptive activity in the abdominal contortion model. In the formalin test, PA-Int5 (at 2.5 and 5 mg/kg) reduced nociception in the second phase. At the higher dose tested, PA-Int5 did not affect spontaneous locomotion or motor coordination. The data revealed that at all doses tested, the compound significantly reduced paw edema following carrageenan administration. In the zymosan-induced air-pouch model, PA-Int5 potently inhibited leukocyte migration and protein levels at the site of inflammation. When combined, the results revealed, for the first time, that PA-Int5 exhibited anti-nociceptive and anti-inflammatory activities, and highlights its potential, as well that of other derivatives, as novel candidates for pain relief.

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“…( 14 ) For example, nitroxide compounds act as antioxidants and have different mechanisms to inhibit gastric ulcers depending on their properties. ( 14 , 15 ) Two spin probes, which were either membrane-permeable or membrane-impermeable probes were also detected simultaneously in the intra- and extracellular compartments of the stomach of rats with indomethacin-induced gastric ulcers and the difference in the suppression of gastric mucosal damage was investigated using a live rat stomach with indomethacin-induced gastric ulcers. ( 15 ) As reported in those papers, observing nitroxides with different tissue permeability is important to know point of action of each nitroxide in gastric mucosa and also useful to understand the detail mechanism of ulcer formation.…”

Section: Introductionmentioning

confidence: 99%

“…There are some reports describing methods for assessing two nitroxides simultaneously with EPR (16) or OMRI. (17,18) These studies utilized two nitroxides either with 14 N or 15 N nitrogen, which gives a different paramagnetic spectrum, enabling simultaneous measurement by OMRI or EPR. However, isotopic labeling method is limited to the number of stable isotopes of each nuclide to detect multiple agents.…”

mentioning

confidence: 99%

Imaging analysis for multiple paramagnetic agents using OMRI and electrophoresis

Enomoto

Kakizawa

Shirouzu

et al. 2022

J. Clin. Biochem. Nutr.

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Nitroxides have been widely used as a molecular probe for analysis of various diseases models. This article describes an analytical method for separation and semi-quantification of multiple paramagnetic contrast agents with simple procedure combining electrophoresis and Overhauser enhancement magnetic resonance imaging (OMRI) imaging. We used three nitroxides, 3-Carbamoyl PROXYL, 3-Carboxy PROXYL, and CAT-1, which have different ionic charges in the molecule. In addition, we showed that this method could apply for in vitro measurement using biological sample. The results showed the nitroxides were successfully separated with electrophoresis depending on their charge, and their separation was visualized with OMRI after electrophoresis. Vehicle media such as whole blood did not affect the electrophoresis results and OMRI enhancement factor. Thus, the method can be used to analyze the redox status of biological samples without preprocessing. This analytical method enables in vitro measurement of biological samples to determine the redox status of specific tissue layers using paramagnetic agents, which is helpful for detailed analysis of redox-related diseases.

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

Abstract: This method may be a very powerful tool for characterizing the pathogenesis of various diseases and may have medical applications. Antioxid. Redox Signal. 00, 000-000.

Cited by 12 publications

References 51 publications

Nitroxyl Radical as a Theranostic Contrast Agent in Magnetic Resonance Redox Imaging

Nitroxyl Radical as a Theranostic Contrast Agent in Magnetic Resonance Redox Imaging

PA‑Int5: An isatin‑thiosemicarbazone derivative that exhibits anti‑nociceptive and anti‑inflammatory effects in Swiss mice

Imaging analysis for multiple paramagnetic agents using OMRI and electrophoresis

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