Effectiveness of carbocysteine lysine salt monohydrate on models of airway inflammation and hyperresponsiveness

Asti, Cinzia; Melillo, G.; Caselli, Gianfranco; Daffonchio, L.; Hernández, Alicia; Clavenna, G.; Omini, C.

doi:10.1016/1043-6618(95)80094-8

Cited by 30 publications

(31 citation statements)

References 12 publications

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“…Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflamma-tory lung diseases such as asthma. Antioxidants which increase cellular cysteine levels, such as N-acetylcysteine (NAC), carbocysteine, and L-2-oxothiazolidine-4-carboxylic acid have been shown to exhibit anti-inflammatory effect and anti-hyperreactivity in animal models of asthma (Asti et al, 1995;Dworski, 2000;Blesa et al, 2002;Lee et al, 2004d). Recently, a novel, low-molecular weight thiol antioxidant, N-acetylcysteine amide (AD4), has been developed (Offen et al, 2004;Grinberg et al, 2005;Penugonda et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

Lee

Kim²,

Park³

et al. 2007

Exp Mol Med

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Reactive oxygen species (ROS) play an important 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 allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-κB and hypoxia-inducible factor-1α (HIF-1α ) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-κB and HIF-1α as well as reducing ROS generation in allergic airway disease.

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Section: Introductionmentioning

confidence: 99%

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

Lee

Kim²,

Park³

et al. 2007

Exp Mol Med

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“…Cysteine derivatives, N-acetylcysteine and carbocysteine, have been used to block inflammation and hyperreactivity in animal models of asthma (Asti et al, 1995;Blesa et al, 2002). 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).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence for increase oxidative stress in asthma is further provided by the finding of defective endogenous antioxidant capacity in asthmatic patients (Dworski, 2000). L-2-Oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine, works as an antioxidant by increasing intracellular glutathione level (Asti et al, 1995;Blesa et al, 2002). OTC raises the plasma concentrations of cysteine, which is the rate-limiting amino acid for intracellular GSH synthesis (Porta et al, 1991;Vita et al, 1998;Oiry et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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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“…In addition to the mucoregulatory action exerted by carbocysteine, the mechanism of action by which it provides anti-inflammatory effects has also been investigated. In pre-clinical and clinical studies, carbocysteine has been shown to reduce neutrophil infiltration into the airway lumen [27], decrease levels of interleukin (IL)-8, IL-6 cytokine levels and 8-isoprostane exhaled in chronic obstructive pulmonary disease [28]. Since the chemotactic recruitment of peripheral blood mononuclear cells into the lung by IL-8 plays a crucial role in the development and maintenance of several inflammatory diseases, the inhibition of IL-8 production may contribute towards the therapeutic effect of SCMC-Lys.…”

Section: Mucoregulatorsmentioning

confidence: 99%

Mucoactive drugs

Balsamo¹,

Lanata²,

Egan³

2010

Eur Respir Rev

125

102

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Mucus hypersecretion is a clinical feature of severe respiratory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Airway mucosal infection and/ or inflammation associated with these diseases often gives rise to inflammatory products, including neutrophil-derived DNA and filamentous actin, in addition to bacteria, apoptotic cells and cellular debris, that may collectively increase mucus production and viscosity. Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus hypersecretion is a clinical complication. The main purpose of mucoactive drugs is to increase the ability to expectorate sputum and/or decrease mucus hypersecretion. Many mucoactive drugs are currently available and can be classified according to their putative mechanism of action. Mucoactive medications include expectorants, mucoregulators, mucolytics and mucokinetics. By developing our understanding of the specific effects of mucoactive agents, we may result in improved therapeutic use of these drugs. The present review provides a summary of the most clinically relevant mucoactive drugs in addition to their potential mechanism of action.

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Effectiveness of carbocysteine lysine salt monohydrate on models of airway inflammation and hyperresponsiveness

Cited by 30 publications

References 12 publications

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

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

Mucoactive drugs

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