Ebselen suppresses late airway responses and airway inflammation in guinea pigs

Zhang, Minjie; Nomura, Akihiro; Uchida, Yoshiyuki; Iijima, Hiroaki; Sakamoto, Tohru; Iishii, Yukio; Morishima, Yuko; Mochizuki, M.; Masuyama, Kuniko; Hirano, Kohji; Sekizawa, Kiyohisa

doi:10.1016/s0891-5849(01)00825-5

Cited by 59 publications

(46 citation statements)

References 41 publications

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“…Level of ROS has been shown to be increased in the airways of OVA-challenged animals (Nishida et al, 2002;Zhang et al, 2002;Lee et al, 2004dLee et al, , 2005Lee et al, , 2006a. ROS released by inflammatory cells infiltrating the airways play an important role in the airway tissue injury observed in asthma (Dworski, 2000).…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…72 It is able to prevent both NFκB/AP-1 activation and proinflammatory gene expression in human leukocytes exposed to peroxynitrite. Other studies have shown that Ebselen is also active in vivo in ameliorating airway inflammation induced by LPS, 73,74 ozone, 75 sephadex, 76 and influenza A virus. 77 Gpx-1 protects against cigarette smoke-induced lung inflammation and damage…”

Section: Therapeutic Intervention With Antioxidantsmentioning

confidence: 96%

Glutathione peroxidase-1 as a novel therapeutic target for COPD

Vlahos

Bozinovski

2013

Redox Report

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Oxidative stress plays a role in a variety of diseases but it is even more pertinent in chronic obstructive pulmonary disease (COPD) given the increased oxidant burden in smokers. The increased oxidant burden results from the fact that cigarette smoke contains over 4700 different chemical compounds and more than 10 15 oxidants/free radicals per puff. Other factors, such as air pollutants, infections, and occupational dusts that may exacerbate COPD, also have the potential to produce oxidative stress. These oxidants give rise to Reactive Oxygen Species (ROS) that are generated enzymatically by inflammatory and epithelial cells within the lung as part of an inflammatory immune response towards a pathogen or irritant. Thus, while ROS are necessary for host defence against invading pathogens, increased levels of ROS have been implicated in initiating inflammatory responses in the lungs through the activation of transcriptional factors, signal transduction pathways, chromatin remodelling and gene expression of proinflammatory mediators. However, the normal lung has developed defences to ROS-mediated damage, which include antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. In this review we consider the therapeutic potential of the antioxidant enzyme glutathione peroxidase-1 for the treatment of cigarette smoke-induced lung inflammation and damage.

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“…Ebselen®, a five-member ring selenium-containing heterocyclic compound showing GPX-like activity (Engman, 1989), is a typical synthetic antioxidant for the scavenging of ROS (Zhang et al, 2002). The antioxidative effects are due to selective blockade of leukocyte infiltration and activation, which results in elimination of these ROS (Zhang et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…The antioxidative effects are due to selective blockade of leukocyte infiltration and activation, which results in elimination of these ROS (Zhang et al, 2002). Thus, ebselen is a multifunctional antioxidant having a potential chemopreventive effect on inflammation (Nakamura et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

A superoxide anion-scavenger, 1,3-selenazolidin-4-one suppresses serum deprivation-induced apoptosis in PC12 cells by activating MAP kinase

Nishina

Kimura

Kozawa

et al. 2011

Toxicology and Applied Pharmacology

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Synthetic organic selenium compounds, such as ebselen, may show glutathione peroxidaselike antioxidant activity and have a neurotrophic effect. We synthesized 1,3-selenazolidin-4-ones, new types of synthetic organic selenium compounds (five-member ring compounds), to study their possible applications as antioxidants or neurotrophic-like molecules. Their superoxide radical scavenging effects were assessed using the quantitative, highly sensitive method of real-time kinetic chemiluminescence. At 166 M, the O2− scavenging activity of 1,3-selenazolidin-4-ones ranged from 0 to 66.2%. 2-[3-(4-Methoxyphenyl)-4-oxo-1,3-selenazolidin-2-ylidene]malononitrile (compound b) showed the strongest superoxide anion-scavenging activity among the 6 kinds of 2-methylene-1,3-selenazolidin-4-ones examined. Compound b had a 50% inhibitory concentration (IC50) at 92.4 M and acted as an effective and potentially useful O2− scavenger in vitro. The effect of compound b on rat pheochromocytome cell line PC12 cells was compared with that of ebselen or nerve growth factor (NGF) by use of the MTT [3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. When ebselen was added at 100 M or more, toxicity toward PC12 cells was evident. On the contrary, compound b suppressed serum deprivation-induced apoptosis in PC12 cells more effectively at a concentration of 100 M. The activity of compound b to phosphorylate mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) 1/2 (MAP kinase) in PC12 cells was higher than that of ebselen, and the former at 100 M induced the phosphorylation of MAP kinase to a degree similar to that induced by NGF. From these results, we conclude that this superoxide anion-scavenger, compound b, suppressed serum deprivationinduced apoptosis by promoting the phosphorylation of MAP kinase. (MAP kinase) in PC12 cells was higher than that of ebselen, and the former at 100 μM induced the phosphorylation of MAP kinase to a degree similar to that induced by NGF.From these results, we conclude that this superoxide anion-scavenger, compound b, suppressed serum deprivation-induced apoptosis by promoting the phosphorylation of MAP kinase.

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Ebselen suppresses late airway responses and airway inflammation in guinea pigs

Cited by 59 publications

References 41 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

Glutathione peroxidase-1 as a novel therapeutic target for COPD

A superoxide anion-scavenger, 1,3-selenazolidin-4-one suppresses serum deprivation-induced apoptosis in PC12 cells by activating MAP kinase

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