The Free Radical Scavenger, α-Lipoic Acid, Protects Against Cerebral Ischemia-Reperfusion Injury in Gerbils

Cao, Xianghui; Phillis, John W.

doi:10.3109/10715769509065257

Cited by 92 publications

(36 citation statements)

References 24 publications

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“…Although OTC or ␣-lipoic acid has been studied clinically for the treatment of oxidant-induced diseases, such as ischemia-reperfusion injury (Cao and Phillis, 1995), diabetic neuropathy (van Dam, 2002), and coronary artery disease (Vita et al, 1998), there are no clinical studies using OTC or ␣-lipoic acid for airway diseases. The calculated human equivalent dose of the murine oral dosage of ␣-lipoic acid in this study is within the reported range of the therapeutic dose of ␣-lipoic acid in human diseases.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Down-Regulates Interleukin-18 Expression in Asthma

et al. 2006

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An alteration in the balance between a T-helper type 2 cell (Th2) response and a Th1 response may predispose to the development of bronchial asthma. Interleukin-18 (IL-18) has an ability to promote both Th1 and Th2 responses, depending on the surrounding cytokine environment. Reactive oxygen species (ROS) play a crucial role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of asthma. In this study, we used a C57BL/6 mouse model of allergic asthma to examine the effects of antioxidants on the regulation of IL-18 expression. Our present study with ovalbumin-induced murine model of asthma revealed that ROS production in cells from bronchoalveolar lavage fluids was increased and that administration of L-2-oxothiazolidine-4-carboxylic acid or ␣-lipoic acid reduced the increased levels of ROS, the increased expression of IL-18 protein and mRNA, airway inflammation, and bronchial hyperresponsiveness. Our results also showed that antioxidants down-regulated a transcription factor, nuclear factor-B (NF-B), activity. These results indicate that antioxidants may reduce IL-18 expression in asthma by inhibiting the activity of NF-B and suggest that ROS regulate the IL-18 expression.

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Section: Discussionmentioning

confidence: 99%

Antioxidant Down-Regulates Interleukin-18 Expression in Asthma

et al. 2006

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“…Previous studies have demonstrated α-lipoic acid cytoprotective action against reperfusion injury in animal models of global 23,24 and focal 25 cerebral ischemia. C -II C-II C-II C -II C -II C -II C -II C -II C -II C -II C -II Groups C -III C -III I-II C -III C -III I -II I -II I -II I -II I -II I -II I -II C -I III -II III -II III -II I - Our demonstrations that 3.03 mM α-lipoic acid infusion promotes initial reduction and final partial EEG spectra mean absolute amplitude recuperation, allowed us to speculate that, in this condition, this substance has an initial pro-oxidant and a late antioxidant action.…”

Section: Discussionmentioning

confidence: 99%

A dual action of alpha-lipoic acid in the brain: an electrophysiological evaluation

Vale

Fonteles²,

Cabral³

et al. 2003

Arq. Neuro-Psiquiatr.

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-Oxidative stress causes metabolic and structural abnormalities during reperfusion. In an animal model of electrophysiological evaluation of cerebral ischemia-reperfusion, α-lipoic acid effect on the oxidative stress was studied by mean absolute amplitude of EEG spectra evaluation. The left carotideal infusion of 3.03 mM α-lipoic acid in Wistar rats after cerebral ischemia and reperfusion caused initial reduction and partial final recuperation of the various EEG spectral frequency mean absolute amplitudes (p<0.05). The left intracarotideal infusion of 6.06 mM α-lipoic acid significantly reverted the induced depression of mean absolute amplitude of theta and delta spectra. Nevertheless there was an increasing pattern of ischemia demonstrated by mean absolute amplitude depression of almost all EEG spectra with 60.6 mM α-lipoic acid infusion. These observations suggest that, depending on the administered concentration, α-lipoic acid may act in a dual way, protecting from ischemia at lower concentrations and worsening this process at higher doses.KEY WORDS: α-lipoic acid, anti-oxidant, pro-oxidant, cerebral ischemia, electroencephalogram (EEG), spectral mean absolute amplitude.Dupla ação do ácido Dupla ação do ácido Dupla ação do ácido Dupla ação do ácido Dupla ação do ácido α α α α α-lipoico no encéfalo: uma avaliação eletrofisiológica -lipoico no encéfalo: uma avaliação eletrofisiológica -lipoico no encéfalo: uma avaliação eletrofisiológica -lipoico no encéfalo: uma avaliação eletrofisiológica -lipoico no encéfalo: uma avaliação eletrofisiológica RESUMO -Estresse oxidativo causa anormalidades metabólicas e estruturais durante reperfusão após isquemia. Em um modelo animal de avaliação eletrofisiológica de isquemia-reperfusão, o efeito da infusão do ácido α-lipóico sobre o estresse oxidativo foi estudado por meio da avaliação da média das amplitudes absolutas dos espectros eletrencefalográficos. A infusão intracarotídea esquerda de ácido α-lipoic 3,03 mM em ratos Wistar após isquemia-reperfusão cerebral causou significante redução inicial e recuperação parcial final da média das amplitudes absolutas dos vários espectros eletro -encefalográficos (p<0,05). A infusão intracarotídea esquerda de ácido α-lipoic 6,06 mM significantemente reverteu a depressão induzida da média das amplitudes absolutas médias dos espectros teta e delta. Houve, contudo, maior depressão da média das amplitudes absolutas de quase todos os espctros com infusão de ácido α-lipóico 60,6 mM. Estas observações sugerem que, dependendo da concentração administrada, o ácido α-lipoic tem duplo efeito, protegendo da isquemia em baixas concentrações e piorando este processo em doses altas. We have previously studied the electroencephalographic effects on mean absolute amplitudes of electroencephalogram (EEG) waves in Wistar rats submitted to global cerebral ischemia due to common carotid arteries ligation, arterial hypotension and reperfusion 1 . There are only few experimental reports in the literature concerning the value of the EEG as a marker ...

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“…The cysteine derivatives N-acetylcysteine and carbocysteine have been used to block inflammation and hyper-reactivity in animal models of asthma (Asti et al, 1995;Blesa et al, 2002). ␣-Lipoic acid, which is a naturally occurring antioxidant, has recently been used clinically for the treatment of oxidant-induced diseases (Cao and Phillis, 1995;Ametov et al, 2003). Cho et al (2004) have shown that ␣-lipoic acid reduces airway inflammation Fig.…”

Section: Discussionmentioning

confidence: 99%

A Prodrug of Cysteine, l-2-Oxothiazolidine-4-carboxylic Acid, Regulates Vascular Permeability by Reducing Vascular Endothelial Growth Factor Expression in Asthma

Lee¹,

Park²,

Park³

et al. 2005

Mol Pharmacol

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Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Oxidative stress plays critical roles in airway inflammation. Although reactive oxygen species (ROS) are shown to cause vascular leakage, the mechanisms by which ROS induce increased vascular permeability are not clearly understood. We have used a murine model of asthma to evaluate the effect of L-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine that acts as an antioxidant, more specifically in the increase of vascular permeability. These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, increased vascular permeability, and increased levels of vascular endothelial growth factor (VEGF). Administration of OTC markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. We also showed that at 72 h after ovalbumin inhalation, increased levels of hypoxia-inducible factor-1␣ (a transcriptional activator of VEGF) in nuclear protein extracts of lung tissues were decreased by the administration of OTC. These results indicate that OTC modulates vascular permeability by lowering VEGF expression.

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The Free Radical Scavenger, α-Lipoic Acid, Protects Against Cerebral Ischemia-Reperfusion Injury in Gerbils

Cited by 92 publications

References 24 publications

Antioxidant Down-Regulates Interleukin-18 Expression in Asthma

Antioxidant Down-Regulates Interleukin-18 Expression in Asthma

A dual action of alpha-lipoic acid in the brain: an electrophysiological evaluation

A Prodrug of Cysteine, l-2-Oxothiazolidine-4-carboxylic Acid, Regulates Vascular Permeability by Reducing Vascular Endothelial Growth Factor Expression in Asthma

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