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Antioxid Redox Signal. 2019 Mar 20;30(9):1147-1161. doi: 10.1089/ars.2017.7336. Epub 2018 May 9.

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

Author information

1
1 Laboratory of Advanced Pharmacology, Daiichi University of Pharmacy, Fukuoka, Japan.
2
2 Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
3
3 Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
4
4 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
5
5 School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

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 15N-labeled TEMPOL and 14N-labeled CAT-1, in addition to imaging with another membrane-permeable 15N-labeled probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL), and 14N-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.

KEYWORDS:

NSAIDs; gastric ulcer; reactive oxygen species; redox imaging; stomach

PMID:
29631421
DOI:
10.1089/ars.2017.7336

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