Dose-dependency of multiple free radical-scavenging activity of edaravone

Tokumaru, Osamu; Shuto, Yachiko; Ogata, Kazuhiro; Kamibayashi, Masato; Bacal, Kira; Takei, Hiroyuki; Yokoi, Isao; Kitano, Takaaki

doi:10.1016/j.jss.2018.03.020

Cited by 24 publications

(16 citation statements)

References 38 publications

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“…Free radicals were measured using an electron spin resonance (ESR) spectrometer (JES-RE1X ESR, JEOL, Tokyo, Japan) with the spin trapping method. (16) The ultraviolet (UV) light source was a 200 W medium-pressure mercury/xenon arc (RUVF-203SR UV illuminator, Radical Research Inc., Tokyo, Japan) with a UV-transmitting/VIS-absorbing filter (230–430 nm). Free radicals were produced in disposable ESR flat cells (Flash Point Inc., Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Each free radical was generated and trapped as previously described. (16–19) Briefly, superoxide anion was produced by the mixture of 0.08 mM hypoxanthine dissolved with phosphate buffer (pH 7.4), 0.04 mM xanthine oxidase, and 2.5 mM CYPMPO as a spin-trap agent. (17) Hydroxyl radical was produced by in situ UV irradiation for 4 s to dilute aqueous solution of hydrogen peroxide (0.3%) in a disposable ESR flat cell and trapped by CYPMPO (2.5 mM).…”

Section: Methodsmentioning

confidence: 99%

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Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

Umeda

Takanari

Ogata

et al. 2019

J. Clin. Biochem. Nutr.

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stricted use, distribution, and reproduction in any medium, provided the original work is properly cited.3 Hydroxy 3 methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (k fv for fluvastatin, and k pv for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with k fv and k pv of 4.82 M −1 s −1 and 49.0 M −1 s −1 , respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both k fv and k pv were >10 9 M −1 s −1 . Fluvastatin also eliminated tert butyl peroxyl radical with relative k fv of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with k fv and k pv of 68.6 M −1 s −1 and 701 M −1 s −1 , respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tert butyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

Umeda

Takanari

Ogata

et al. 2019

J. Clin. Biochem. Nutr.

Self Cite

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“…Edaravone (ED) is a free radical scavenger that protects the cerebral functions, and is a first-line drug in clinical treatment of cerebral infarction (Parikh et al, 2017; Tokumaru et al, 2018). ED scavenges free radicals, inhibits lipid peroxidation and alleviates ischemia-reperfusion injury (Fujisawa & Yamamoto, 2016; Uchiyama et al, 2015) , moreover, as it has antioxidant properties, ED is the first free radical scavenger clinically proved to be a neuroprotective agent in Japan since 2001 (Minnelli et al, 2019) , and it plays an important role in alleviating oxidative stress in some diseases (Kikuchi et al, 2012) .…”

Section: Introductionmentioning

confidence: 99%

Edaravone reduces oxidative stress and intestinal cell apoptosis after burn through up-regulating miR-320 expression

Bian

Liu

et al. 2019

Mol Med

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BackgroundIntestinal mucosa barrier dysfunction after burn injury is an important factor for causing mortality of burn patients. The current study established a burn model in rats and used a free radical scavenger edaravone (ED) to treat the rats, so as to investigate the effect of edaravone on intestinal mucosa barrier after burn injury.MethodsAnesthetized rats were subjected to 40% total body surface area water burn immediately, followed by treatment with ED, scrambled antagomir, or antagomiR-320. Intestinal mucosa damage was observed by hematoxylin-eosin staining and graded by colon mucosal damage index (CMDI) score. The contents of total sulfhydryl (TSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were determined by spectrophotometry. Cell apoptosis, protein relative expression,and the in situ expressions of p-Akt and p-Bad were detected by flow cytometry, Western blotting and immunohistochemistry, respectively. The miR-320 expression was determined by quantitative real-time polymerase chain reaction.ResultsED alleviated intestinal mucosal damage caused by burn injury, down-regulated the levels of MDA, cytochrome C, cleaved caspase-9 and cleaved caspase-3, but up-regulated the levels of TSH, SOD, CAT and Bcl-2. We also found that ED could reduce oxidative stress, inhibit cell apoptosis, increase the expressions of p-Akt, p-Bad and miR-320, and decrease PTEN expression. PTEN was predicted to be the target gene for miR-320, and cell apoptosis could be promoted by inhibiting miR-320 expression.ConclusionED regulates Akt/Bad/Caspase signaling cascade to reduce apoptosis and oxidative stress through up-regulating miR-320 expression and down-regulating PTEN expression, thus protecting the intestinal mucosal barrier of rats from burn injury.

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“…Compounds 3 , 5d–j and 5l (IC 50 : 9.5–19 µM) exhibited similar or greater antioxidant activity when compared to the control, Trolox (IC 50 = 13.1 µM). In addition, these compounds retained the antioxidant activity of edaravone (IC 50 = 4.7 µM) 65 . Compound 5j had the best IC 50 of 9.5 µM.…”

Section: Resultsmentioning

confidence: 94%

“… c IC 50 values of donepezil reported by reference [ 64 ]. d IC 50 values of edaravone reported by reference [ 65 ]. n.d.: not determined.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluation of edaravone derivatives bearing the N-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents

Zondagh

Malan

Joubert

2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of multi-target directed edaravone derivatives bearing N-benzyl pyridinium moieties were designed and synthesised. Edaravone is a potent antioxidant with significant neuroprotective effects and N-benzyl pyridinium has previously exhibited positive results as part of a dual-site binding, peripheral anionic site (PAS) and catalytic anionic site (CAS), acetylcholinesterase (AChE) inhibitor. The designed edaravone-N-benzyl pyridinium hybrid compounds were docked within the AChE active site. The results indicated interactions with conserved amino acids (Trp279 in PAS and Trp84 in CAS), suggesting good dualsite inhibitory activity. Significant in vitro AChE inhibitory activities were observed for selected compounds (IC 50 : 1.2-4.6 mM) with limited butyrylcholinesterase inhibitory activity (IC 50 's >160 mM), indicating excellent selectivity towards AChE (SI: 46->278). The compounds also showed considerable antioxidant ability, similar to edaravone. In silico studies indicated that these compounds should cross the blood-brain barrier, making them promising lead molecules in the development of anti-Alzheimer's agents.

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Dose-dependency of multiple free radical-scavenging activity of edaravone

Cited by 24 publications

References 38 publications

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

Edaravone reduces oxidative stress and intestinal cell apoptosis after burn through up-regulating miR-320 expression

Design, synthesis and biological evaluation of edaravone derivatives bearing the N-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents

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