MCI-186 (edaravone), a novel free radical scavenger, protects against acute autoimmune myocarditis in rats

2005 ◽  
Vol 289 (6) ◽  
pp. H2514-H2518 ◽  
Author(s):  
Masaomi Nimata ◽  
Taka-aki Okabe ◽  
Miki Hattori ◽  
Zuyi Yuan ◽  
Keisuke Shioji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Hydroxyl Radicals ◽  
Radical Scavenging ◽  
Weight Ratio ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Cytotoxic Activities ◽  
Thiobarbituric Acid Reactive Substance ◽  
Autoimmune Myocarditis

In this study, we tested the hypothesis that MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one; edaravone), a novel free radical scavenger, protects against acute experimental autoimmune myocarditis (EAM) in rats by the radical scavenging action associated with the suppression of cytotoxic myocardial injury. Recent evidence suggests that oxidative stress may play a role in myocarditis. We administered MCI-186 intraperitoneally at 1, 3, and 10 mg·kg−1·day−1 to rats with EAM for 3 wk. The results were compared with untreated rats with EAM. MCI-186 treatment did not affect hemodynamics. MCI-186 treatment (3 and 10 mg·kg−1·day−1) reduced the severity of myocarditis as assessed by comparing the heart-to-body weight ratio and pathological scores. Myocardial interleukin-1β (IL-1β)-positive cells and myocardial oxidative stress overload with DNA damage in rats with EAM given MCI-186 treatment were significantly less compared with those of the untreated rats with EAM. In addition, MCI-186 treatment decreased not only the myocardial protein carbonyl contents but also the myocardial thiobarbituric acid reactive substance products in rats with EAM. The formation of hydroxyl radicals in MCI-186-treated heart homogenates was decreased compared with untreated heart homogenates. Furthermore, cytotoxic activities of lymphocytes of rats with EAM treated with MCI-186 were significantly lower compared with those of the untreated rats with EAM. Hydroxyl radicals may be involved in the development of myocarditis. MCI-186 protects against acute EAM in rats associated with scavenging hydroxyl free radicals, resulting in the suppression of autoimmune-mediated myocardial damage associated with reduced oxidative stress state.

CHARACTERISTICS AND THERAPEUTIC EFFECTS OF THE NOVEL FREE RADICAL SCAVENGER – EDARAVONE

2020 ◽  
Vol 04 (05) ◽  
pp. 17-20
Author(s):  
Mirza Mikayil Aliyev ◽  
◽  
Ulduz Yunis Safarova ◽  
Shafiqa Jahangir Jafarova ◽  
◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Arachidonic Acid ◽  
Free Radical ◽  
Hydroxyl Radicals ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Therapeutic Effects ◽  
The Novel ◽  
Prostacyclin Production

Edaravone is the first free radical scavenger which approved clinically and has an ability to decrease the level of free radicals in cells. Edaravone is a strong antioxidant, which can protect different cells (e.g. endothelial cells) against damage by ROS by inhibiting the lipoxygenase metabolism of arachidonic acid, by trapping hydroxyl radicals, by increasing prostacyclin production, by inhibiting alloxan-induced lipid peroxidation, etc. Because of that, Edaravone is used in treatment of diseases which are associated with oxidative stress. Key words: edaravone, free radical, antioxidant, neuroprotective agent, oxidative stress

scholarly journals Resveratrol Prevents Cataract Formation by Inhibiting Pro-inflammatory Mediator-induced Dysregulation of Lens Calcium

2020 ◽  
Vol 2 (3) ◽  
pp. 14-35
Author(s):  
R. Manikandan
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Free Radical ◽  
Radical Scavenging ◽  
Free Radical Scavenger ◽  
Eye Lens ◽  
Radical Scavenger ◽  
Cataract Formation ◽  
Rat Pups ◽  
Radical Generation

The effect of resveratrol, a free radical scavenger, during cataract development was evaluated in the Wistar rat pup model. This study investigated the possible free radical scavenging potential of resveratrol at 40 mg/ kg body wt dose in selenite-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 µm mol/ kg body wt) in 8 to 10 day old rat pups lead to severe oxidative stress in the tissues evidenced by decreased antioxidants and increased lipid peroxidase, nitric oxide, superoxide anion, hydroxyl radical generation, inducible nitric oxide synthase (iNOS) as well as nuclear factor kappa B (NF-kB) expression levels that probably led to cataract formation. Selenite exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca2+ ATPase but not Na+/ K+ ATPase or Mg2+ ATPase. However, both pre- and co-treatments with resveratrol, but not post-treatment, led to an increase in antioxidant levels with a concomitant reduction in oxidative stress and also rescued the selenite-mediated increase in lens Ca2+ and inhibition of Ca2+ ATPase activity in the eye lens. The results of this study demonstrate antioxidants decrease and increase in free radical generation triggered by selenite causes the inactivation of lens Ca2+ ATPase leading to a rise in intracellular Ca2+ level. Resveratol treatment was able to prevent selenite-induced oxidative stress and in turn the inhibition of lens opacification. Thus, resveratrol has the potential to function as an anti-cataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca2+ in the eye lens.

scholarly journals Free Radical–Mediated Cell Damage After Experimental Status Epilepticus in Hippocampal Slice Cultures

2002 ◽  
Vol 88 (6) ◽  
pp. 2909-2918 ◽  
Author(s):  
Richard Kovács ◽  
Sebastian Schuchmann ◽  
Siegrun Gabriel ◽  
Oliver Kann ◽  
Julianna Kardos ◽  
...  
Keyword(s):  
Free Radicals ◽  
Status Epilepticus ◽  
Free Radical ◽  
Hippocampal Slice ◽  
Cell Damage ◽  
Radical Scavenging ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Mitochondrial Depolarization ◽  
Hippocampal Slice Cultures

Generation of free radicals may have a key role in the nerve cell damage induced by prolonged or frequently recurring convulsions (status epilepticus). Mitochondrial function may also be altered due to production of free radicals during seizures. We therefore studied changes in field potentials (fp) together with measurements of extracellular, intracellular, and intramitochondrial calcium concentration ([Ca2+]e, [Ca2+]i, and [Ca2+]m, respectively), mitochondrial membrane potential (ΔΨ), NAD(P)H auto-fluorescence, and dihydroethidium (HEt) fluorescence in hippocampal slice cultures by means of simultaneous electrophysiological and microfluorimetric measurements. As reported previously, each seizure-like event (SLE) resulted in mitochondrial depolarization associated with a delayed rise in oxidation of HEt to ethidum, presumably indicating ROS production. We show here that repeated SLEs led to a decline in intracellular and intramitochondrial Ca2+ signals despite unaltered Ca2+ influx. Also, mitochondrial depolarization and the NAD(P)H signal became smaller during recurring SLEs. By contrast, the ethidium fluorescence rises remained constant or even increased from SLE to SLE. After about 15 SLEs, activity changed to continuous afterdischarges with steady depolarization of mitochondrial membranes. Staining with a cell death marker, propidium iodide, indicated widespread cell damage after 2 h of recurring SLEs. The free radical scavenger, α-tocopherol, protected the slice cultures against this damage and also reduced the ongoing impairment of NAD(P)H production. These findings suggest involvement of reactive oxygen species (ROS) of mitochondrial origin in the epileptic cell damage and that free radical scavenging may prevent status epilepticus–induced cell loss.

scholarly journals Hydroxyl radical induced structural changes of collagen

2007 ◽  
Vol 21 (2) ◽  
pp. 91-103 ◽  
Author(s):  
Helan Xiao ◽  
Guoping Cai ◽  
Mingyao Liu
Keyword(s):  
Free Radical ◽  
Hydroxyl Radicals ◽  
Structural Changes ◽  
Type I Collagen ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Type I ◽  
Dependent Manner ◽  
First Time

Extracellular matrix (ECM) plays an important role in cell differentiation, growth, migration and apoptosis. Collagen is the most abundant protein familyin vivo, but its function has still not been clearly defined yet. Reactive oxygen species (ROS) have a central role in oxidative cell stress. Electron spin resonance (ESR) spectroscopy indicates that type I collagen could uniquely scavenge hydroxyl radicals in dose- and time-dependent manner; whereas BSA and gelatin (a denatured collagen) have no such an effect. However, the mechanism by which type I collagen scavenges hydroxyl radicals is different from that of GSH, a well-known free radical scavenger. Using a new method, two-dimensional FTIR correlation analysis, for the first time, we show that the order of functional group changes of type I collagen in this process is amide I earlier than amide II than amide III than –CH– thanν(C=O). The results indicates that the structure of the main chain of collagen changed first, followed by more residue groupν(C=O) exposed to hydroxyl radicals. The reaction with the carbonyl group in collagen causes the hydroxyl free radicals to be scavenged. Therefore, ECM can effectively scavenge ROS under normal physiological conditions. When the proteins of ECM were denatured in the same way as gelatin, they lost their function as a free radical scavenger. All of these results provide new insight into therapy or prevention of oxidative stress, apoptosis and ageing.

scholarly journals Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone)

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tomomi Masuda ◽  
Masamitsu Shimazawa ◽  
Hideaki Hara
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Apoptotic Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Free Radical Scavenger ◽  
Age Related Macular Degeneration ◽  
Radical Scavenger ◽  
Retinal Diseases ◽  
Age Related

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress.

Arjunic Acid, a Strong Free Radical Scavenger from Terminalia arjuna

2008 ◽  
Vol 36 (01) ◽  
pp. 197-207 ◽  
Author(s):  
Fang-Yun Sun ◽  
Xiu-Ping Chen ◽  
Jin-Hua Wang ◽  
Hai-Lin Qin ◽  
Su-Rong Yang ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Free Radical ◽  
Radical Scavenging ◽  
Free Radical Scavenging ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Dpph Method ◽  
Significant Difference

This study was designed to investigate the antioxidant and free radical scavenging capacities of arjunic acid, an aglycone obtained from the fruit of medicine Terminalia Fruit. Liver microsomes, mitochondria, and red blood cells (RBCs) were prepared from Wistar rats. The antioxidant capacity was determined by the inhibitory effect on lipid peroxidation, hydrogen peroxide induced RBCs hemolysis, and RBCs autoxidative hemolysis. The free radical scavenging activity was tested by DPPH method and 2′,7′-dichlorodihydrofluoresc in diacetate (DCFH2-DA) assay. Ascorbic acid was chosen as the positive controls. Results showed that arjunic acid was a strong antioxidant and a free radical scavenger, more potent than ascorbic acid, in microsomes lipid peroxidation, DPPH, hydrogen peroxide induced RBCs hemolysis, and (DCFH2-DA) assay (p < 0.05). However, no significant difference was observed in the RBCs autoxidative hemolysis assay (p > 0.05).

DPPH Free Radical Scavenger Components from the Fruits of Alpinia rafflesiana Wall. ex. Bak. (Zingiberaceae)

2004 ◽  
Vol 59 (11-12) ◽  
pp. 811-815 ◽  
Author(s):  
Habsah Mohamad ◽  
Faridah Abas ◽  
Dharma Permana ◽  
Nordin H. Lajis ◽  
Abdul Manaf Ali ◽  
...  
Keyword(s):  
Free Radical ◽  
Methanol Extract ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Free Radical Scavenging ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Scavenging Activity ◽  
Colorimetric Analysis ◽  
Natural Sources

The methanol extract of the dried ripe fruits of Alpinia rafflesiana was investigated for its DPPH free radical scavenger constituents. 2′,3′,4′,6′-Tetrahydroxychalcone (7), which has never been isolated from natural sources was found to be most active as a DPPH free radical scavenger with the IC50 value of 55 μᴍ. Other known compounds isolated from this species include 5,6-dehydrokawain (1), flavokawin B (2), 1,7-diphenyl-5-hydroxy-6-hepten-3-one (3), (-)-pinocembrin (4), cardamonin (5) and (-)-pinostrobin (6). The DPPH free radical scavenger compounds were detected using TLC autographic analysis. The percentage inhibition of DPPH free radical scavenging activity was measured on isolates (5-7) using colorimetric analysis.

scholarly journals Hot Topics and Challenges of Regenerative Nanoceria in Application of Antioxidant Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Changyan Li ◽  
Xiangcheng Shi ◽  
Qiudi Shen ◽  
Chen Guo ◽  
Zepeng Hou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Delivery ◽  
Tissue Engineering ◽  
Free Radical ◽  
Radiation Protection ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Redox Cycle ◽  
Related Disease ◽  
Resistance To Oxidation

As a new antioxidant, nanoceria is of significant importance in applications of medical and biological fields. In comparison with conventional organic antioxidants, nanoceria has multienzyme mimetic activity by Ce4+/Ce3+ redox cycle. This unique regenerative/autocatalytic property has been widely used in the aspects of free-radical scavenger, radiation protection, oxidative-stress-related disease, drug delivery, biosensor, tissue engineering, cancer biomarker, and anti-inflammatory. This paper reviews the latest breakthrough of nanoceria as an antioxidant in applications of medical and biological fields on the base of the authors’ research works on resistance to oxidation and cytotoxicity. The challenges of nanoceria encountered in applications in medical and biological fields are commented as well.

scholarly journals Celastrol and Melatonin Modify SIRT1, SIRT6 and SIRT7 Gene Expression and Improve the Response of Human Granulosa-Lutein Cells to Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1871
Author(s):  
Rita Martín-Ramírez ◽  
Rebeca González-Fernández ◽  
Jairo Hernández ◽  
Pablo Martín-Vasallo ◽  
Angela Palumbo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Free Radical ◽  
Cell Survival ◽  
Direct Effect ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Protective Agent ◽  
Physiological Processes

An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins’ gene expression.

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