Administration of l-2-oxothiazolidine-4-carboxylate increases glutathione levels in rat brain

Mesina, J.E.; Page, R. H.; Hetzel, Fred W.; Chopp, Michael

doi:10.1016/0006-8993(89)91494-7

Cited by 44 publications

(22 citation statements)

References 14 publications

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“…Previous studies have demonstrated that OTC is more effective than N-acetylcysteine in replenishing intracellular GSH stores (Williamson and Meister, 1981;Mesina et al, 1989) and blocks airway hyperresponsiveness and inflammation in an asthmatic animal model (Lee et al, 2004c). Consistent with previous observations, administration of OTC decreases airway inflammation.…”

Section: Discussionsupporting

confidence: 87%

An antioxidant modulates expression of receptor activator of NF-κB in asthma

Lee

Park²,

Park³

et al. 2006

Exp Mol Med

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Oxidative stress plays critical roles in airway inflammation that is usually accompanied by increased vascular permeability and plasma exudation. VEGF increases vascular permeability and leads to airway inflammation. In addition, VEGF has been shown to enhance receptor activator of NF-κB (RANK) expression in endothelial cells. An aim of the study was to determine the potential role of antioxidant in the regulation of RANK expression in murine model of asthma. We have used a C57BL/6 mouse model of allergic asthma to evaluate the effect of L-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine, which acts as an antioxidant, and VEGF receptor inhibitor on RANK mRNA expression. The mice develop the following pathophysiological features of asthma in the lungs: increased expression of RANK mRNA, increased number of inflammatory cells of the airways, increased vascular permeability, and increased levels of VEGF. Administration of OTC and VEGF receptor inhibitor markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. We also showed that the increased RANK mRNA expression at 72 h after ovalbumin inhalation were reduced by the administration of OTC or VEGF receptor inhibitor. The results indicate that OTC and VEGF receptor inhibitor which inhibit up-regulation of VEGF expression modulate RANK expression that may be in association with the regulation of vascular permeability, and suggest that VEGF may regulate the RANK expression. These findings provide a crucial molecular mechanism for the potential use of antioxidants to prevent and/or treat asthma and other airway inflammatory disorders.

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Section: Discussionsupporting

confidence: 87%

An antioxidant modulates expression of receptor activator of NF-κB in asthma

Lee

Park²,

Park³

et al. 2006

Exp Mol Med

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“…Several studies have demonstrated that OTC is more effective than N-acetylcysteine in replenishing intracellular glutathione stores (Williamson and Meister, 1981;Mesina et al, 1989) and blocks airway hyper-responsiveness and inflammation in an asthmatic animal model (Lee et al, 2004b). OTC, a thiazolidine derivative, is a prodrug of cysteine that raises the plasma concentrations of cysteine and glutathione (Porta et al, 1991;Vita et al, 1998;Oiry et al, 1999).…”

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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“…Several studies have also demonstrated that OTC repletes cellular GSH stores when GSH is acutely depleted (Hazelton et al, 1986;Moslen et al, 1989) and is more effective than N-acetylcysteine in repleting intracellular GSH stores (Williamson et al, 1982;Mesina et al, 1989). In addition, ␣-lipoic acid is reduced intracellularly to dihydrolipoic acid by lipoamide dehydrogenase.…”

Section: Antioxidant and Il-18 In Asthma 1191mentioning

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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Administration of l-2-oxothiazolidine-4-carboxylate increases glutathione levels in rat brain

Cited by 44 publications

References 14 publications

An antioxidant modulates expression of receptor activator of NF-κB in asthma

An antioxidant modulates expression of receptor activator of NF-κB in asthma

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

Antioxidant Down-Regulates Interleukin-18 Expression in Asthma

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