A multiple free-radical scavenging (MULTIS) study on the antioxidant capacity of a neuroprotective drug, edaravone as compared with uric acid, glutathione, and trolox. Kamogawa Erisa,Sueishi Yoshimi Bioorganic & medicinal chemistry letters Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) is a neuroprotective drug that has been used for brain ischemia injury treatment. Because its activity is speculated to be due to free radical scavenging activity, we carried out a quantitative determination of edaravone's free radical scavenging activity against multiple free radical species. Electron spin resonance (ESR) spin trapping-based multiple free-radical scavenging (MULTIS) method was employed, where target free radicals were hydroxyl radical, superoxide anion, alkoxyl radical, alkylperoxyl radical, methyl radical, and singlet oxygen. Edaravone showed relatively high scavenging abilities against hydroxyl radical (scavenging rate constant k=2.98×10(11) M(-1) s(-1)), singlet oxygen (k=2.75×10(7) M(-1) s(-1)), and methyl radical (k=3.00×10(7) M(-1) s(-1)). Overall, edaravone's scavenging activity against multiple free radical species is as robust as other known potent antioxidant such as uric acid, glutathione, and trolox. A radar chart illustration of the MULTIS activity relative to uric acid, glutathione, and trolox indicates that edaravone has a high and balanced antioxidant activity with low specificity. 10.1016/j.bmcl.2014.01.045

Associations between Uric Acid Level and 3-Month Functional Outcome in Acute Ischemic Stroke Patients Treated with/without Edaravone. Naganuma Masaki,Inatomi Yuichiro,Nakajima Makoto,Yonehara Toshiro,Ando Yukio Cerebrovascular diseases (Basel, Switzerland) BACKGROUND:Uric acid (UA), an antioxidant with neuroprotective effects, favorably affects stroke outcome. However, the effect has not been examined in patients treated with edaravone, a frequently used free radical scavenger. We investigated whether the use of edaravone affected the relationship between UA levels and outcome in acute ischemic stroke. METHODS:We retrospectively evaluated 1,114 consecutive ischemic stroke patients with premorbid modified Rankin Scale (mRS) scores <2 admitted within 24 h of onset (mean, 74 years; median UA levels, 333 μmol/L). We divided the patients into 2 groups using the median UA value as a cutoff, a low UA group (≤333 μmol/L; n = 566) and a high UA group (>333 μmol/L; n = 548), and compared their clinical characteristics and favorable outcomes (mRS <2) at 90 days. We investigated the associations between UA levels and 90-day stroke outcome in patients with and without edaravone treatment. RESULTS:The high UA group had a higher proportion of men, hypertension, atrial fibrillation, and cardioembolic stroke than the low UA group. The high UA group also had a higher proportion of patients with mRS <2 at 90 days (61.5 vs. 54.1%, p = 0.013), but the significance was diminished in multivariate analysis (OR 1.30, 95% CI 0.94-1.71). In subgroup analysis, the high UA group without edaravone exhibited a higher proportion of patients with mRS <2 at 90 days than the low UA group (OR 2.87, 95% CI 1.20-7.16). The high UA group with edaravone did not exhibit this difference. CONCLUSIONS:In acute ischemic stroke, the favorable association between high UA levels and outcome at 90 days was not evident in patients treated with edaravone. 10.1159/000488038

Plasma marker of tissue oxidative damage and edaravone as a scavenger drug against peroxyl radicals and peroxynitrite. Yamamoto Yorihiro Journal of clinical biochemistry and nutrition The percentage of the plasma oxidized form of coenzyme Q10 in the total amount of coenzyme Q10 (%CoQ) is a useful marker of oxidative stress in the circulation. Plasma free fatty acids and their composition can be used as markers of tissue oxidative damage, as demonstrated in patients suffering from a wide variety of diseases and in humans and rats under oxidative stress. Edaravone was approved for the treatment of stroke in Japan in 2001 and its mechanism of action is based on scavenging lipid peroxyl radicals. In 2015, edaravone was also approved for the treatment of ALS patients. Edaravone functions therapeutically as a scavenger of peroxynitrite, as demonstrated by the finding that its administration raises plasma uric acid levels and decreases 3-nitrotyrosine in cerebrospinal fluid. 10.3164/jcbn.16-63

Edaravone, a potent free radical scavenger, reacts with peroxynitrite to produce predominantly 4-NO-edaravone. Fujisawa Akio,Yamamoto Yorihiro Redox report : communications in free radical research OBJECTIVES:3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is used in clinical treatment of acute brain infarction to rescue the penumbra, based on its ability to prevent lipid peroxidation by scavenging lipid peroxyl radicals. Here, we show that edaravone also reacts with peroxynitrite to yield 4-NO-edaravone as the major product and 4-NO2-edaravone as a minor product. RESULTS:We observed little formation of 3-methyl-1-phenyl-2-pyrazolin-4,5-dione (4-oxoedaravone) and its hydrate, 2-oxo-3-(phenylhydrazono)butanoic acid, which are the major free radical-induced oxidation products of edaravone, suggesting that free radicals are not involved in the reaction with peroxynitrite. The reaction of peroxynitrite with edaravone is approximately 30-fold greater than with uric acid, a physiological peroxynitrite scavenger (reaction rate k = 1.5 × 10 (4)  M(-1) s(-1) vs. 480 M(-1) s(-1)). DISCUSSION:These results suggest that edaravone functions therapeutically as a scavenger of peroxynitrite as well as lipid peroxyl radicals, which is consistent with a report that edaravone treatment reduced levels of 3-nitrotyrosine in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis. 10.1179/1351000215Y.0000000025