Redox-Based Theranostics of Gastric Ulcers Using Nitroxyl Radicals.

Redox-based theranostics involves redox monitoring and therapeutics that normalize redox imbalance. It may be a promising approach to markedly improve a patient's quality of life through streamlined treatment. Nitroxyl radicals are useful for both redox monitoring and treating gastric ulcers in rodents.

[Free Radical Production and Production Mechanism in the Early and Advanced Stages of Gastrointestinal Lesions].

Disruption of redox balance due to the overproduction of free radicals and reactive oxygen species (ROS) could cause protein denaturation, lipid peroxidation, and DNA mutation. These lead to an induction of gastrointestinal diseases such as gastric ulcers induced by long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) and ulcerative colitis. Magnetic resonance technique, which is non-invasive and free of radiation exposure, is a promising tool for evaluating redox status in the living body.

Electricity use is associated with residents' vital data and lifestyles: observational study using an IT health support system in Japan.

Motivated by developments in information technology, recording personal parameters with health devices is effective in health promotion. Today's indoor individual lifestyles often involve using electrical appliances. We developed a health support system combined with wireless electricity monitoring and investigated whether electricity use is associated with residents' vital data and lifestyles.

Dynamic nuclear polarization magnetic resonance imaging and the oxygen-sensitive paramagnetic agent OX63 provide a noninvasive quantitative evaluation of kidney hypoxia in diabetic mice.

Renal hypoxia may play an important role in the progression of diabetic nephropathy. However, tools that noninvasively and quantitatively measure oxygen tension in the kidney are lacking. Here, we evaluated the feasibility of a noninvasive and quantitative imaging technique using dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) in combination with the oxygen-sensitive paramagnetic agent OX63 for measuring oxygen tension in the kidney.

In vivo redox imaging of dextran sodium sulfate-induced colitis in mice using Overhauser-enhanced magnetic resonance imaging.

In ulcerative colitis, an inflammatory bowel disease of unknown cause, diagnosis of the degree and location of colitis at an early stage is required to control the symptoms. Changes in redox status, including the production of reactive oxygen and nitrogen species (RONS), have been associated with ulcerative colitis in humans and dextran sodium sulfate (DSS)-induced colitis in rodents. In this study, the in vivo redox status of colons of DSS-induced colitis mice were monitored by Overhauser-enhanced magnetic resonance imaging (OMRI), and the relationship between redox status and colitis development was investigated.

Nitric Oxide Is Involved in Activation of Toll-Like Receptor 4 Signaling through Tyrosine Nitration of Src Homology Protein Tyrosine Phosphatase 2 in Murine Dextran Sulfate-Induced Colitis.

Ulcerative colitis is characterized by colonic mucosal bleeding and ulceration, often with repeated active and remission stages. One factor in ulcerative colitis development is increased susceptibility to commensal bacteria and lipopolysaccharide (LPS). LPS activates macrophages to release nitric oxide (NO) through Toll-like receptor 4 (TLR4) signaling.

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

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.

[Development of Redox Metabolic Imaging Using Endogenous Molecules].

Redox metabolism plays a central role in maintaining homeostasis in living organisms. The electron transfer system in mitochondria produces ATP via endogenous redox molecules such as flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and coenzyme Q10 (CoQ10), which have flavin or quinone moieties. One-electron transfer reactions convert FMN, FAD, and CoQ10 to the free radical intermediates FMNH and FADH, and CoQ10H, respectively.

Redox imaging of skeletal muscle using in vivo DNP-MRI and its application to an animal model of local inflammation.

Disorders of skeletal muscle are often associated with inflammation and alterations in redox status. A non-invasive technique that could localize and evaluate the severity of skeletal muscle inflammation based on its redox environment would be useful for disease identification and monitoring, and for the development of treatments; however, no such technique currently exists. We describe a method for redox imaging of skeletal muscle using dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), and apply this method to an animal model of local inflammation.

Simultaneous and spectroscopic redox molecular imaging of multiple free radical intermediates using dynamic nuclear polarization-magnetic resonance imaging.

Redox reactions that generate free radical intermediates are essential to metabolic processes. However, their intermediates can produce reactive oxygen species, which may promote diseases related to oxidative stress. We report here the use of dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) to conduct redox molecular imaging.

Involvement of nitric oxide with activation of Toll-like receptor 4 signaling in mice with dextran sodium sulfate-induced colitis.

Ulcerative colitis is an inflammatory bowel disease characterized by acute inflammation, ulceration, and bleeding of the colonic mucosa. Its cause remains unknown. Increases in adhesion molecules in vascular endothelium, and activated neutrophils releasing injurious molecules such as reactive oxygen species, are reportedly associated with the pathogenesis of dextran sodium sulfate (DSS)-induced colitis.

Benefit of azilsartan on blood pressure elevation around rest-to-active phase in spontaneously hypertensive rats.

Abnormal elevation of blood pressure in early morning (rest-to-active phase) is suggested to cause cardiovascular events. We investigated whether azilsartan (AZL), a novel potent angiotensin receptor blocker, suppresses blood pressure elevation from the light-rest to dark-active phase in spontaneously hypertensive rats (SHRs). AZL has a sustained depressor effect around the rest-to-active phase in SHRs to a greater extent than candesartan (CAN), despite their similar depressor effects for over 24 h.

In vivo imaging of tumor physiological, metabolic, and redox changes in response to the anti-angiogenic agent sunitinib: longitudinal assessment to identify transient vascular renormalization.

Aims: The tumor microenvironment is characterized by a highly reducing redox status, a low pH, and hypoxia. Anti-angiogenic therapies for solid tumors frequently function in two steps: the transient normalization of structurally and functionally aberrant tumor blood vessels with increased blood perfusion, followed by the pruning of tumor blood vessels and the resultant cessation of nutrients and oxygen delivery required for tumor growth. Conventional anatomic or vascular imaging is impractical or insufficient to distinguish between the two steps of tumor response to anti-angiogenic therapies.

Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

Objectives: Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved.

The detrimental effect of nitric oxide on tissue is associated with inflammatory events in the vascular endothelium and neutrophils in mice with dextran sodium sulfate-induced colitis.

Nitric oxide (NO) is thought to be a key molecule in the progression of ulcerative colitis and experimental colitis induced by dextran sodium sulfate (DSS). However, the detrimental effect of DSS-induced NO production on the colonic mucosa is incompletely understood. Increases in the expression of adhesion molecules in the vascular endothelium and activated neutrophils (thereby releasing injurious molecules such as reactive oxygen species) are reportedly associated with the pathogenesis of DSS-induced colitis.

Whole-body kinetic image of a redox probe in mice using Overhauser-enhanced MRI.

Overhauser-enhanced MRI (OMRI) enables visualization of free radicals in animals based on dynamic nuclear polarization. Real-time data of tissue redox status gathered from kinetic images of redox-sensitive nitroxyl radical probes using OMRI provided both anatomic and physiological information. Phantom experiments demonstrated the linear correlation between the enhancement factor and the concentration of a membrane-impermeable probe, carboxy-PROXYL (3-carboxy-2,2,5,5-tetramethyl- pyrrolidine-1-oxyl).

Combination therapy of olmesartan and azelnidipine inhibits sympathetic activity associated with reducing oxidative stress in the brain of hypertensive rats.

It has been demonstrated that the antihypertensive drugs with the antioxidant action on the brainstem inhibit the sympathetic activity and consequently decrease blood pressure and heart rate (HR) in hypertensive rats. Combination drugs of the angiotensin receptor blocker and calcium channel blocker, such as olmesartan (OLM)/azelnidipine (AZ) and candesartan (CAN)/amlodipine (AM), are widely used for treating hypertension in Japan. In this study, it was investigated whether there are differences in the antioxidant effect in the brain and the sympathoinhibitory effect between OLM/AZ and CAN/AM combination therapies in stroke-prone spontaneously hypertensive rats (SHRSP).

Imaging in vivo redox status in high spatial resolution with OMRI.

Redox-reactions are playing a significant role in regulation of homeostasis of organism. Disorder of the redox-status is related with the onset and/or propagation of oxidative diseases such as lifestyle-related diseases, including cancers and cardiac diseases, etc. In vivo imaging of redox-status is thereby important in the analysis of mechanisms of oxidative diseases and developments of new medicines for the diseases.

Nitroxides prevent exacerbation of indomethacin-induced gastric damage in adjuvant arthritis rats.

Nonsteroidal anti-inflammatory drugs are the drugs of choice in the treatment of rheumatoid arthritis (RA) because of their rapid analgesic effect. However, they induce severe gastric damage in RA patients and animals by a process mediated by reactive oxygen species (ROS). Nitroxides (nitroxyl radicals) are widely used as imaging agents and antioxidants to explore the role of ROS generation in the pathogenesis of disease.

Aripiprazole inhibits superoxide generation from phorbol-myristate-acetate (PMA)-stimulated microglia in vitro: implication for antioxidative psychotropic actions via microglia.

Altered antioxidant status has been implicated in schizophrenia. Microglia, major sources of free radicals such as superoxide (•O(2)(-)), play crucial roles in various brain pathologies. Recent postmortem and imaging studies have indicated microglial activation in the brain of schizophrenic patients.

Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method.

We previously showed that oxidative stress in the brain is involved in the neural mechanisms of hypertension. Therefore, olmesartan, an angiotensin type 1 receptor blocker, might affect oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). Here, we evaluated the effects of olmesartan treatment using an in vivo electron spin resonance (ESR)/spin probe technique.

Non-invasive monitoring of redox status in mice with dextran sodium sulphate-induced colitis.

Change of redox status is associated with colitis induced by dextran sodium sulphate (DSS). This study monitored redox status in DSS-induced colitis in mice using in vivo electron spin resonance (ESR) spectroscopy with nitroxyl probes. Colitis was induced in male ICR mice by supplementing their drinking water with 3% DSS for 3, 5 or 7 days.

[Analysis of in vivo redox status with magnetic resonance technique].

In vivo redox reaction is involved in processes of oxidative diseases. The redox imaging technique is important to diagnose redox-induced diseases and to assess cure effects of pharmaceutical drugs. A group of nitroxyl radicals is sensitive to redox reactions and we have investigated mechanisms of oxidative diseases, including diabetes, ischemia reperfusion injuries and gastric ulcer.