Stable nitroxide Tempol ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischemia

Kato, Noriyuki; Yanaka, Kiyoyuki; Hyodo, Koji; Homma, Kazuhiro; Nagase, Sohji; Nose, Tadao

doi:10.1016/s0006-8993(03)02918-4

Cited by 61 publications

(46 citation statements)

References 25 publications

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“…Lipid peroxidation and protein tyrosine nitrosylation are two markers for oxidative and nitrosative tissue damage in the brain [28,29]. In this study, CI/Rinduced cerebral lipid peroxidation, as assayed by MDA formation, occurred in a time-dependent manner that peaked at 24 h as in our previous report [27].…”

Section: Protective Effects Of Taxifolin Against Ci/r-induced Oxidatisupporting

confidence: 70%

Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation

Wang¹,

et al. 2005

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SummaryInfarction in adult rat brain was induced by middle cerebral arterial occlusion (MCAO) followed by reperfusion to examine whether taxifolin could reduce cerebral ischemic reperfusion (CI/R) injury. Taxifolin administration (0.1 and 1.0 lg/kg, i.v.) 60 min after MCAO ameliorated infarction (by 42%±7% and 62%±6%, respectively), which was accompanied by a dramatic reduction in malondialdehyde and nitrotyrosine adduct formation, two markers for oxidative tissue damage. Overproduction of reactive oxygen species (ROS) and nitric oxide (NO) via oxidative enzymes (e.g., COX-2 and iNOS) was responsible for this oxidative damage. Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration. ROS, generated by leukocytes and microglial cells, activated nuclear factor-kappa B (NF-jB) that in turn signaled up-regulation of inflammatory proteins. NF-jB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin. Production of both ROS and NO by leukocytes and microglial cells was significantly antagonized by taxifolin. These data suggest that amelioration of CI/R injury by taxifolin may be attributed to its antioxidative effect, which in turn modulates NF-jB activation that mediates CI/R injury.

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Section: Protective Effects Of Taxifolin Against Ci/r-induced Oxidatisupporting

confidence: 70%

Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation

Wang¹,

et al. 2005

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“…[2][3][4] We have also demonstrated the accumulation of lipid peroxidation products and the decrease in antioxidative enzymes in the ischemic hemispheres in our model at 2 days after MCAO and reperfusion. Previous studies have already reported the direct neuroprotective effects of CCBs during the early phase of ischemia reperfusion.…”

Section: Discussionsupporting

confidence: 57%

“…The ischemic lesions in T2-weighted imaging were defined as hyperintense areas on the image. To measure the ischemic lesion volume, the outline of the hyperintensive area was traced on the MRI, and then the sum of the areas gave the volume of the ischemic lesion volume in mm 3 .…”

Section: Estimation Of Ischemic Lesion Volume By Mrimentioning

confidence: 99%

“…1 Oxidative stress has an important role in the pathogenesis of ischemic brain damage. [2][3][4] During ischemia, a robust influx of calcium (Ca 2+ ) activates glutamate receptors that induce the generation of reactive oxygen species from mitochondria 5 and reactive nitrogen species, 6 leading to lipid peroxidation. 7 L-type Ca 2+ channels and N-methyl-D-aspartate receptors have a crucial role in the entry of Ca 2+ into neurons.…”

Section: Introductionmentioning

confidence: 99%

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Nifedipine treatment reduces brain damage after transient focal ischemia, possibly through its antioxidative effects

et al. 2011

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Stroke is a major cause of mortality and morbidity in hypertensive patients. This study investigated the effects of nifedipine, an L-type voltage-gated Ca 2+ channel blocker, on ischemic lesion volume after focal cerebral ischemia and reperfusion in rats. Rats were subjected to 1 h of transient middle cerebral artery occlusion (MCAO). At 2 days after MCAO, the rats were randomized into two groups that were fed either a normal control diet (n¼10) or a nifedipine (0.001%) containing diet (n¼11) for 2 weeks. Nifedipine treatment significantly reduced ischemic lesion volume (116.5 ± 10.8 vs. 80.0 ± 8.2 mm 3 , Po0.05) without affecting body weight or blood pressure. It also decreased thiobarbituric-reactive substances, an index of lipid peroxide, (2.6 ± 0.4 vs. 1.7 ± 0.1 lmol g À1 tissue, Po0.05) and increased glutathione peroxidase (54.9 ± 4.7 vs. 70.9 ± 6.4 U g À1 protein, Po0.05) and glutathione reductase activities (32.4 ± 1.4 vs. 39.9 ± 2.7 U g À1 protein, Po0.05) in the mitochondria from the ischemic hemispheres. These results suggest that nifedipine treatment can reduce ischemic lesion volume after focal cerebral ischemia, possibly because of the decrease in oxidative stress with an increase in antioxidant activities within the ischemic area.

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“…Tempol treatment resulted in a significant, dose-dependent decrease in infarct size as measured by digital imaging of brain slices which were collected and fixed after four hours of reperfusion ( Figure 11). Post-ischemic ROS formation and lipid peroxidation was also prevented using Tempol in a study of transient cerebral ischemia in rats as measured by assessing 2,3-dihydroxybenzoic acid levels and thiobarbituric acid reactive substances [71]. Acute subdural hematoma can also result in local cerebral ischemia and O 2 • − mediated damage.…”

Section: Ischemia-reperfusion Injury and Inflammationmentioning

confidence: 99%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

453

387

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Cyclic nitroxides are a diverse range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described including their ability to degrade superoxide and peroxide, inhibit Fenton reactions and undergo radical-radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. While much remains to be done, many applications have been well studied and some are presently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials.

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Stable nitroxide Tempol ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischemia

Cited by 61 publications

References 25 publications

Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation

Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation

Nifedipine treatment reduces brain damage after transient focal ischemia, possibly through its antioxidative effects

The chemistry and biology of nitroxide compounds

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