Edaravone, a novel radical scavenger, inhibits oxidative modification of low-density lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the expression of endothelial nitric oxide synthase

Yoshida, Hiroshi; Sasaki, Kayoko; Namiki, Yoshihisa; Sato, Noriko; Tada, Norio

doi:10.1016/j.atherosclerosis.2004.10.037

Cited by 60 publications

(39 citation statements)

References 26 publications

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“…In this respect, our findings are consistent with the dual role hypothesized for oxidative stress and can be interpreted in two ways: i) the changes in NO metabolism and oxidative stress markers may simply reflect the different severity of ischemic damage in lacunar and non-lacunar stroke, or, more intriguingly, ii) they might also play an additive role in promoting and sustaining tissue damage. The latter hypothesis is supported by experimental work demonstrating that antioxidant therapy administered in the early phase of ischemic damage may be critical for improving outcome [11,25,27]. Our finding of a correlation between reduced plasma NO and unfavorable clinical evolution in non-lacunar stroke suggest at least a role for NO metabolism changes in the pathophysiology of ischemic injury evolution.…”

Section: Discussionsupporting

confidence: 60%

Plasma levels of nitric oxide and stroke outcome

et al. 2007

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Production of reactive oxygen species after cerebral blood flow disruption may enhance tissue damage through multiple molecular pathways. Changes in nitric oxide (NO) metabolism and oxidative stress status were investigated in 47 patients with ischemic stroke by measuring plasma nitric oxide (NO) and peroxynitrite (ONOO(-)) levels.A correlation was sought between these two parameters and i) baseline stroke severity based on the National Institute of Health stroke scale (NIHSS) and ii) neurological outcome in terms of NIHSS changes from entry (T(0)) to 30 days after symptom onset (T(1)). The control group consisted of 30 age- and sex-matched healthy subjects. Mean plasma levels of ONOO(-) (arbitrary fluorescence number +/- SD) were significantly higher in patients (7.70 +/- 1.71 vs 5.35 +/- 0.69, p < 0.001), whereas mean NO levels (nmol/mg protein) were significantly higher in controls (115.40 +/- 12.40 vs. 51.10 +/- 12.50, p < 0.001). Plasma ONOO(-) was significantly higher among patients with non-lacunar stroke (8.48 +/- 1.50 vs. 6.95 +/- 1.58 in those with lacunar stroke; p = 0.001), whereas NO levels were significantly higher among lacunar stroke patients (60.00 +/- 7.86, vs. 41.77 +/- 9.29 in patients with nonlacunar stroke; p < 0.001). Nitric oxide plasma levels were also associated with an unfavorable evolution in non-lacunar stroke, since a 10 unit increase in NO predicted a 1 point reduction in the NIHSS score at T1. Findings show that changes in NO metabolism may be considered as markers of brain injury in patients with ischemic stroke. Further work is needed to establish whether the amount of biochemical changes related to oxidative stress may influence outcome in these patients.

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Section: Discussionsupporting

confidence: 60%

Plasma levels of nitric oxide and stroke outcome

et al. 2007

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“…Previous studies from our institution have also demonstrated a decrease in eNOS protein expression in ischemic myocardium following I / R (7,8). An in vitro study in HUVEC has shown that edaravone may increase eNOS expression via the inhibition of LDL oxidation (25). Thus, the burst of ROS generation during I / R may cause cell injury that results in reduced eNOS production, and edaravone administration preserves the eNOS expression.…”

Section: Edaravone Preserves Nitric Oxide and Enosmentioning

confidence: 74%

Edaravone Preserves Coronary Microvascular Endothelial Function After Ischemia/Reperfusion on the Beating Canine Heart In Vivo

et al. 2007

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Abstract. We examined whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, exerts its protective effect on coronary microvessels after ischemia / reperfusion (I/ R) in vivo. Ninety-minute coronary occlusion followed by reperfusion was performed in 16 open-chest dogs with and without edaravone administration. Coronary small artery (≥100 µm in size) and arteriolar (<100 µm) vasodilation, in the presence of endothelium-dependent (acetylcholine) or -independent (papaverine) vasodilators, was directly observed using intravital microscopy before and after I / R. I / R impaired microvascular vasodilation in response to acetylcholine, whereas administration of edaravone preserved the response in microvessels of both sizes, but to a greater extent in the coronary small arteries. No significant changes were noted with papaverine administration. In the edaravone group, the fluorescent intensity from reactive oxygen species (ROS) was lower, whereas nitric oxide (NO) intensity was higher relative to controls in the microvessels of the ischemic area. In conclusion, edaravone preserves coronary microvascular endothelial function after I / R in vivo. These effects, which were NOmediated, were attributed to the ROS scavenging properties of edaravone.

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“…7 In addition, edaravone has been reported to increase endothelial nitric oxide synthase (eNOS) in rat vascular endothelial cells and to enhance NO production in a rat model of carotid endarterial injury. 8,9 In the light of these fi ndings, it is unlikely that edaravone causes renal disorders through a reduction in renal blood fl ow rate.…”

Section: Discussionmentioning

confidence: 99%