Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction

Líu, Hao; Uno, Masaaki; Kitazato, Keiko T.; Suzue, Atsuhiko; Manabe, Shiji; Yamasaki, Hiroyuki; Shono, Masayuki; Saijo, Nagahiro

doi:10.1016/j.brainres.2004.07.071

Cited by 61 publications

(47 citation statements)

References 30 publications

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“…We performed 3-hour middle cerebral artery occlusion (MCAO) by inserting an intraluminal filament as described previously. 13 Briefly, male Wistar rats weighing 250 to 280 g were anesthetized and the right occipital artery and the external carotid artery (ECA) were ligated and isolated. To block major collateral flow the pterygopalatine artery was ligated at its origin.…”

Section: Transient Cerebral Ischemia Modelmentioning

confidence: 99%

“…9 Edaravone may prevent such cell injuries and suppress neuronal death and brain edema by scavenging free radicals such as a peroxy-and hydroxyl radicals and by inhibiting lipid peroxidation. 10 -12 We previously demonstrated oxidant damage in ischemic rat brain lesions 13 ; in patients with acute cerebral infarction, oxidative brain damage was inhibited by edaravone. 14 In a rat model, edaravone inhibited rtPA-induced intracerebral hemorrhage.…”

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confidence: 97%

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Edaravone, a Free Radical Scavenger, Inhibits MMP-9–Related Brain Hemorrhage in Rats Treated With Tissue Plasminogen Activator

Yagi

Kitazato

Uno

et al. 2009

Stroke

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139

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Background and Purpose-Intracerebral hemorrhage, induced by recombinant tissue plasminogen activator (rtPA) in ischemic stroke, is attributable to the increased activity of matrix metalloproteinase-9 (MMP-9). Patients with acute infarct benefit from the neuroprotective drug edaravone, a free radical scavenger. We examined the mechanisms by which edaravone may help to suppress rtPA-induced brain hemorrhage. Methods-Male Wistar rats weighing 250 to 280 g were subjected to 3-hour transient middle cerebral artery occlusion (MCAO) and divided randomly into 3 groups. Immediately after reperfusion, 1 group was intravenously injected with 10 mg/kg rtPA, another with rtPA plus 3 mg/kg edaravone, and the 3rd group received no treatment. We assessed the hemorrhage volume and the activity of MMP-9 in the brain 24 hours postischemia. We also studied the activity of MMP-9, its mRNA expression, and nuclear factor-kappa B (NF-B) activity in rtPA-stimulated human microvascular endothelial cells (HBECs). Results-The degree of hemorrhage and the level of endothelial cell-derived MMP-9 were elevated in rats treated with rtPA alone and attenuated in rats treated with rtPA plus edaravone. In rtPA-stimulated HBECs, edaravone suppressed the activity and mRNA expression of MMP-9 in a dose-dependent manner. Edaravone also inhibited NF-B activation. Conclusions-We demonstrate that edaravone inhibits rtPA-induced cerebral hemorrhage in the ischemic brain of rats via the inhibition of MMP-9 expression in vivo, which is substantiated by inhibition of MMP-9 expression and NF-B activation in HBECs. Edaravone may render thrombolytic therapy safer for the administration of rtPA in patients with ischemic stroke.

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Section: Transient Cerebral Ischemia Modelmentioning

confidence: 99%

mentioning

confidence: 97%

Edaravone, a Free Radical Scavenger, Inhibits MMP-9–Related Brain Hemorrhage in Rats Treated With Tissue Plasminogen Activator

Yagi

Kitazato

Uno

et al. 2009

Stroke

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139

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“…8-hydroxydeoxyguanosine (8-OHdG) is an oxidized nucleoside that is excreted in the bodily fluids with DNA repair. Several studies have demonstrated that 8-OHdG in bodily fluids can act as a biomarker of oxidative stress (Chiou et al 2003;Liu et al 2004;Wu et al 2004) and 8-OHdG is commonly used as a marker to evaluate oxidative DNA damage in disorders including chronic inflammatory diseases (Chapple and Matthews 2007).…”

Section: Introductionmentioning

confidence: 99%

Increased salivary level of 8-hydroxydeoxyguanosine is a marker of premature oxidative mitochondrial DNA damage in gingival tissue of patients with periodontitis

Çanakçı

Tatar

et al. 2009

Arch. Immunol. Ther. Exp.

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Introduction: Oxidative stress may contribute to the pathogenesis of periodontitis. However, the detailed molecular mechanism remains unclear. Both 8-hydroxydeoxyguanosine (8-OHdG) and mitochondrial DNA (mtDNA) deletion have been reported as early oxidative DNA damage markers. In this study, 8-OHdG levels in saliva and mtDNA deletions in gingival tissue of patients with chronic periodontitis (CP) were evaluated. Materials and Methods: Gingival tissue and whole saliva samples were collected from 32 patients with CP and 32 healthy control subjects. To determine the clinical condition of each subject, the plaque index, gingival index, clinical attachment level (CAL), and probing depth (PD) were measured. Using the ELISA and polymerase chain reaction methods, the salivary 8-OHdG levels and the 7.4-kbp and 5-kbp mtDNA deletions were examined. Results: The 5-kbp mtDNA deletion was detected in 20 of the 32 periodontitis patients (62.5%), but was not detected in the healthy controls. The mean value of 8-OHdG in the saliva of the periodontitis patients with deleted mtDNA was significantly higher than in the patients with non-deleted mtDNA (p<0.01). Also, significant correlation was found between the occurrence of the 5-kbp mtDNA deletion and salivary 8-OHdG levels (p<0.01). Similar correlations were detected between salivary 8-OHdG levels and age, PD, and CAL (p<0.01, p<0.05). Conclusion: Increased oxidative stress may lead to premature oxidative DNA damage in the gingival tissue of periodontitis patients and the salivary 8-OHdG level may signify premature oxidative mtDNA damage in diseased gingival tissue.

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“…There is evidence that oxidative DNA damage is an early and potentially reversible event in ischaemic brain injury. In contrast, DNA degradation occurs at a relatively later stage of neuronal apoptotic and necrotic cell death (Chen et al 1997;Liu et al 2004). In our experimental model, we have observed that the lymphocyte levels of 8-oxoG from animals with I/R of brain was significantly increased at the end of ischaemia and remained elevated at the first measurement after starting reperfusion (3 h).…”

Section: Discussionmentioning

confidence: 71%

Time Course of Peripheral Oxidative Stress as Consequence of Global Ischaemic Brain Injury in Rats

et al. 2007

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Free radicals play an important role in the pathogenesis of brain injury. This study evaluates the potential relationship between ischaemia/reperfusion (I/R)-induced brain injury, peripheral oxidative stress (lymphocyte DNA damage), plasma antioxidant potential and uric acid levels. We observed that 15 min of ischaemia were sufficient to significantly increase lymphocyte DNA damage that remained elevated at the end of early (3 h) reperfusion and at later (72 h) reperfusion time; this parameter was not significantly increased, when compared to preoperated levels. In parallel, antioxidant potential was elevated after 15 min of ischaemia, remained high at early (3 h) reperfusion and decreased again with longer (72 h) reperfusion. A close association between the plasma antioxidant status and the uric acid content has been confirmed by findings that changes in TRAP values positively correlate with uric acid concentration in rat plasma after ischaemic injury. Moreover, results of in vitro experiments with extra uric acid addition to control plasma have shown that uric acid contributes to a greater part of TRAP values. These results indicate a similar time course of brain I/R-associated oxidative stress and peripheral antioxidant defence status and/or oxidative stress in animal experiments.

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Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction

Cited by 61 publications

References 30 publications

Edaravone, a Free Radical Scavenger, Inhibits MMP-9–Related Brain Hemorrhage in Rats Treated With Tissue Plasminogen Activator

Edaravone, a Free Radical Scavenger, Inhibits MMP-9–Related Brain Hemorrhage in Rats Treated With Tissue Plasminogen Activator

Increased salivary level of 8-hydroxydeoxyguanosine is a marker of premature oxidative mitochondrial DNA damage in gingival tissue of patients with periodontitis

Time Course of Peripheral Oxidative Stress as Consequence of Global Ischaemic Brain Injury in Rats

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