Carbocisteine can scavenge reactive oxygen species <i>in vitro</i>

Nogawa, Hisashi; Ishibashi, Yuji; Ogawa, Akitsu; Masuda, Kayoko; Tsubuki, Takeshi; Kameda, Tomoko; Matsuzawa, Shigeki

doi:10.1111/j.1440-1843.2008.01424.x

Cited by 29 publications

(29 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, CARB, at the selected concentration (10 −4 M), resulted less potent in controlling ROS formation in a nasal epithelial cell line and in another airway epithelial cell line (Nogawa et al 2009). Furthermore, in bronchial epithelial cells, carbocysteine, but not FP, was able to counteract the oxidant activities of CSE, also increasing GSH, HO-1 and Nrf2.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Pace

Ferraro

Vincenzo

et al. 2013

Cell Stress and Chaperones

View full text Add to dashboard Cite

Cigarette smoke extracts (CSE) induce oxidative stress, an important feature in chronic obstructive pulmonary disease (COPD), and oxidative stress contributes to the poor clinical efficacy of corticosteroids in COPD patients. Carbocysteine, an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on CSE-induced oxidative stress in bronchial epithelial cells as well as the comparison of these antioxidant effects of carbocysteine with those of fluticasone propionate are unknown. The present study was aimed to assess the effects of carbocysteine (10 −4 M) in cell survival and intracellular reactive oxygen species (ROS) production (by flow cytometry) as well as total glutathione (GSH), heme oxygenase-1 (HO-1), nuclearrelated factor 2 (Nrf2) expression and histone deacetylase 2 (HDAC-2) expression/activation in CSE-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate (10 −8 M). CSE, carbocysteine or fluticasone propionate did not induce cell necrosis (propidium positive cells) or cell apoptosis (annexin Vpositive/propidium-negative cells) in 16-HBE. CSE increased ROS production, nuclear Nrf2 and HO-1 in 16-HBE. Fluticasone propionate did not modify intracellular ROS production, GSH and HDCA-2 but reduced Nrf2 and HO-1 in CSE-stimulated 16-HBE. Carbocysteine reduced ROS production and increased GSH, HO-1, Nrf2 and HDAC-2 nuclear expression/activity in CSE-stimulated cells and was more effective than fluticasone propionate in modulating the CSEmediated effects. In conclusion, the present study provides compelling evidences that the use of carbocysteine may be considered a promising strategy in diseases associated with corticosteroid resistance.

show abstract

Section: Discussionmentioning

confidence: 96%

“…16-HBE, an immortalised normal bronchial epithelial cell line (Cozens et al 1992), RPMI 2650a, a nasal epithelial cell line (Pace et al 2012a), and a mucin-producing human NCI-H292 airway epithelial cell line (Nogawa et al 2009) were used in this study.…”

Section: Stimulation Of Epithelial Cell Linesmentioning

confidence: 99%

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Pace

Ferraro

Vincenzo

et al. 2013

Cell Stress and Chaperones

View full text Add to dashboard Cite

show abstract

“…Consistent with literature reports [1,2] , we found that carbocisteine was effective in reducing the rate of acute exacerbations and improving quality of life in patients with chronic obstructive pulmonary disease (COPD) in a large-scale multi-center clinical trial [3] . Despite the lack of a free thiol group, carbocisteine harbors a thioether group that can be oxidized by reactive oxygen species (ROS) [4] . Carbocisteine reportedly scavenged H 2 O 2 , HOCl, OH* and ONOO -in cell-free medium, inhibited ROS production in rat neutrophils [4] , promoted GSH and HO-1 expression in cigarette smoke-exposed bronchial epithelial cells [5] , and ameliorated oxidant-induced 16HBE cell apoptosis [6] .…”

Section: Introductionmentioning

confidence: 99%

Carbocisteine attenuates TNF-α-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-κB and ERK1/2 MAPK signaling pathways

et al. 2016

View full text Add to dashboard Cite

Aim: We previously proven that carbocisteine, a conventional mucolytic drug, remarkably reduced the rate of acute exacerbations and improved the quality of life in the patients with chronic obstructive pulmonary disease. In this study we investigated the mechanisms underlying the anti-inflammatory effects of carbocisteine in human alveolar epithelial cells in vitro. Methods: Human lung adenocarcinoma cell line A549 was treated with TNF-α (10 ng/mL). Carbocisteine was administered either 24 h prior to or after TNF-α exposure. The cytokine release and expression were measured using ELISA and qRT-PCR. Activation of NF-κB was analyzed with Western blotting, immunofluorescence assay and luciferase reporter gene assay. The expression of ERK1/2 MAPK signaling proteins was assessed with Western blotting. Results: Carbocisteine (10, 100, 1000 µmol/L), administered either before or after TNF-α exposure, dose-dependently suppressed TNF-α-induced inflammation in A549 cells, as evidenced by diminished release of IL-6 and IL-8, and diminished mRNA expression of IL-6, IL-8, TNF-α, MCP-1 and MIP-1β. Furthermore, pretreatment with carbocisteine significantly decreased TNF-α-induced phosphorylation of NF-κB p65 and ERK1/2 MAPK, and inhibited the nuclear translocation of p65 subunit in A549 cells. In an NF-κB luciferase reporter system, pretreatment with carbocisteine dose-dependently inhibited TNF-α-induced transcriptional activity of NF-κB. Conclusion: Carbocisteine effectively suppresses TNF-α-induced inflammation in A549 cells via suppressing NF-κB and ERK1/2 MAPK signaling pathways.

show abstract

“…L-Carbocisteine inhibits inflammation associated with influenza virus infection and chronic obstructive pulmonary disease (Yasuda et al, 2006;Zheng et al, 2008;Yamaya et al, 2010;Asada et al, 2012), suppresses oxaliplatininduced hepatocyte toxicity by inhibiting oxaliplatin-induced decreases in the Bcl2/Bim ratio, and inhibits oxaliplatininduced apoptosis in vitro . Moreover, L-carbocisteine possesses free radical-scavenging and antiinflammatory properties in vitro (Zheng et al, 2008;Nogawa et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, novel biologic activities of L-carbocisteine have been reported in the context of inhibition of inflammation associated with influenza virus infection and chronic obstructive pulmonary disease (Yasuda et al, 2006;Zheng at al., 2008;Yamaya et al, 2010;Asada et al, 2012). Another report showed that L-carbocisteine possessed free radical-scavenging properties in vitro (Nogawa et al, 2009). Various inflammatory cells, including neutrophils, mast cells, natural killer cells, macrophages, and dendritic cells, are involved in the induction and promotion of angiogenesis (Noonan et al, 2008;Kim et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Orally Administered Mucolytic Drug l-Carbocisteine Inhibits Angiogenesis and Tumor Growth in Mice

Shinya

Yokota

Nakayama

et al. 2015

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Angiogenesis, the formation of new blood vessels from preexisting vessels, is essential for the growth and metastasis of tumors. In this study, we found that L-carbocisteine, a widely used expectorant, potently inhibits angiogenesis in vitro and in vivo. An in vivo Matrigel plug assay revealed that L-carbocisteine (2.5 mg/kg i.p. twice daily) significantly inhibited vascular endothelial growth factor (VEGF)-induced angiogenesis. L-Carbocisteine also suppressed VEGF-stimulated proliferation, migration, and formation of capillary-like structures of human umbilical vein endothelial cells (HUVECs). We examined the signaling pathways affected in VEGF-stimulated HUVECs, and found that L-carbocisteine significantly inhibited VEGF-induced phosphorylation of phospholipase C (PLC) g, protein kinase C (PKC) m, and extracellular signal-related kinases (ERK) 1/2, which have been shown to be essential for angiogenesis. However, these inhibitory effects of L-carbocisteine were not observed in the HeLa human cervical cancer cell line. An in vivo study of Colon-26 tumor-bearing mice found that tumor volumes were significantly smaller in mice treated with L-carbocisteine (150 mg/kg administered orally twice daily) in comparison with vehicle-treated mice. However, L-carbocisteine had no direct effect on Colon-26 cell proliferation or ERK activation. Collectively, our results suggest that L-carbocisteine inhibits tumor angiogenesis by suppressing PLCg/PKC/ERK signaling.

show abstract

Carbocisteine can scavenge reactive oxygen species in vitro

Abstract: These results suggest that carbocisteine could exert anti-inflammatory and anti-oxidant effects through directly scavenging ROS in addition to its previously known mucoregulatory effect.

Cited by 29 publications

References 21 publications

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Carbocisteine attenuates TNF-α-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-κB and ERK1/2 MAPK signaling pathways

Orally Administered Mucolytic Drug l-Carbocisteine Inhibits Angiogenesis and Tumor Growth in Mice

Contact Info

Product

Resources

About