Quercetin attenuates airway inflammation and mucus production induced by cigarette smoke in rats

Yang, Ting; Luo, Feng; Shen, Yongchun; An, Jing; Li, Xiaoou; Liu, Xinyu; Ying, Binwu; Liao, Zenglin; Dong, Jiajia; Guo, Lingli; Wang, Tao; Xu, Dan; Chen, Lei; Wen, Fuqiang

doi:10.1016/j.intimp.2012.03.006

Cited by 49 publications

(32 citation statements)

References 28 publications

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“…This substantially negative finding is not surprising. In fact, the cigarette smoke-activated EGFR was not inhibited by the tyrosine kinase inhibitors AG1478, erlotinib, and gefitinib in lung epithelial cells (7), in spite of the fact that EGFR and its downstream signaling are increased in the bronchial epithelium of smokers (40,41) as well as in the lungs of smoke-exposed rats (42). In addition, lapatinib did not induce a significant number of tumor regressions in NSLC in a phase II trial (9).…”

Section: Discussionmentioning

confidence: 97%

Assay of lapatinib in murine models of cigarette smoke carcinogenesis

et al. 2014

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Lapatinib, a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), is prescribed for the treatment of patients with metastatic breast cancer overexpressing HER-2. Involvement of this drug in pulmonary carcinogenesis has been poorly investigated. We used murine models suitable to evaluate cigarette smoke-related molecular and histopathological alterations. A total of 481 Swiss H mice were used. The mice were exposed to mainstream cigarette smoke (MCS) during the first four months of life. After 10 weeks, MCS caused an elevation of bulky DNA adducts, oxidative DNA damage and an extensive downregulation of microRNAs in lung. After four months, an increase in micronucleus frequency was observed in peripheral blood erythrocytes. After 7.5 months, histopathological alterations were detected in the lung, also including benign tumors and malignant tumors, and in the urinary tract. A subchronic toxicity study assessed the non-toxic doses of lapatinib, administered daily with the diet after weaning. After 10 weeks, lapatinib significantly attenuated the MCS-related nucleotide changes and upregulated several low-intensity microRNAs in lung. The drug poorly affected the MCS systemic genotoxicity and had modest protective effects on MCS-induced preneoplastic lesions in lung and kidney, when administered under conditions that temporarily mimicked interventions either in current smokers or exsmokers. On the other hand, it caused some toxicity to the liver. Thus, on the whole, lapatinib appears to have a low impact in the smoke-related lung carcinogenesis models used, especially in terms of tumorigenic response.

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Section: Discussionmentioning

confidence: 97%

Assay of lapatinib in murine models of cigarette smoke carcinogenesis

et al. 2014

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“…These oxidants and a network of inflammatory cytokines participate in the recruitment of neutrophils and other inflammatory cells into lungs [17], resulting in airway narrowing and alveolar wall damage [3]. Our research group previously described a rat model system in which chronic exposure to CS recapitulates the morphological and functional changes of human chronic airway diseases, including oxidative stress, evidenced by decreased T-AOC and total GSH levels; increased levels of (CINC)-1, TNF-α, and cell counts in BALF; thickening of the airway epithelium; peribronchial inflammatory cell infiltration and goblet cell hyperplasia [5]. The present study extends the earlier work by showing that the morphological and inflammatory changes induced by chronic CS exposure are accompanied by higher lung MPO activity and increases in pro-inflammatory cytokines (TNF-α, IL-1β, and IL-8) in BALF.…”

Section: Discussionmentioning

confidence: 99%

“…We have studied the possible activities of quercetin, a plant flavonoid, on airway inflammation induced by CS in rats [5]. As a result of our investigations, we have found that quercetin blocked oxidative stress and the airway inflammatory response in the rat model.…”

Section: Introductionmentioning

confidence: 91%

Silymarin Attenuates Airway Inflammation Induced by Cigarette Smoke in Mice

Wang

et al. 2014

Inflammation

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Cigarette smoke (CS), which increases inflammation and oxidative stress, is a major risk factor for the development of COPD. In this study, we investigated the effects of silymarin, a polyphenolic flavonoid isolated from the seeds and fruits of milk thistle, on CS-induced airway inflammation and oxidative stress in mice and the possible mechanisms. BALB/c mice were exposed to CS for 2 h twice daily, 6 days per week for 4 weeks. Silymarin (25, 50 mg/kg·day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and the detection of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination, myeloperoxidase (MPO) activity assay, superoxide dismutase (SOD) activities, and malondialdehyde (MDA) levels. The phosphorylation of ERK and p38 was evaluated by Western blotting. Pretreatment with silymarin significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction. The numbers of total cells, macrophages, and neutrophils, along with the MPO activity (a marker of neutrophil accumulation) in BALF, were remarkably decreased by silymarin in CS-exposed mice (all p<0.05). In addition, silymarin pretreatment dampened the secretion of TNF-α, IL-1β, and IL-8 in BALF. High-dose silymarin (50 mg/kg·day) administration also prevented CS-induced elevation in MDA levels and decrease in SOD activities (p<0.05). Furthermore, the CS-induced phosphorylation of ERK and p38 was also attenuated by silymarin (p<0.05). These results suggest that silymarin attenuated inflammation and oxidative stress induced by cigarette smoke. The anti-inflammatory effect might partly act through the mitogen-activated protein kinases (MAPK) pathway.

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“…Human mucoepidermoid pulmonary carcinoma cell line NCI-H292 (H292) has been used in a number of studies of pulmonary inflammation and/or eicosanoid production (88)(89)(90)(91)(92), as well as in studies of pulmonary infection by bacteria (93)(94)(95). These cells were cultured in RPMI 1640 medium (American Type Culture Collection, Manassas, VA) supplemented with 10% fetal bovine serum, 2 mM L-glutamine, and penicillin-streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Cytosolic Phospholipase A₂α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae Infection

et al. 2017

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Pulmonary infection by Streptococcus pneumoniae is characterized by a robust alveolar infiltration of neutrophils (polymorphonuclear cells [PMNs]) that can promote systemic spread of the infection if not resolved. We previously showed that 12-lipoxygenase (12-LOX), which is required to generate the PMN chemoattractant hepoxilin A 3 (HXA 3 ) from arachidonic acid (AA), promotes acute pulmonary inflammation and systemic infection after lung challenge with S. pneumoniae. As phospholipase A 2 (PLA 2 ) promotes the release of AA, we investigated the role of PLA 2 in local and systemic disease during S. pneumoniae infection. The group IVA cytosolic isoform of PLA 2 (cPLA 2 ␣) was activated upon S. pneumoniae infection of cultured lung epithelial cells and was critical for AA release from membrane phospholipids. Pharmacological inhibition of this enzyme blocked S. pneumoniae-induced PMN transepithelial migration in vitro. Genetic ablation of the cPLA 2 isoform cPLA 2 ␣ dramatically reduced lung inflammation in mice upon high-dose pulmonary challenge with S. pneumoniae. The cPLA 2 ␣-deficient mice also suffered no bacteremia and survived a pulmonary challenge that was lethal to wild-type mice. Our data suggest that cPLA 2 ␣ plays a crucial role in eliciting pulmonary inflammation during pneumococcal infection and is required for lethal systemic infection following S. pneumoniae lung challenge.

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Quercetin attenuates airway inflammation and mucus production induced by cigarette smoke in rats

Cited by 49 publications

References 28 publications

Assay of lapatinib in murine models of cigarette smoke carcinogenesis

Assay of lapatinib in murine models of cigarette smoke carcinogenesis

Silymarin Attenuates Airway Inflammation Induced by Cigarette Smoke in Mice

Cytosolic Phospholipase A₂α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae Infection

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Quercetin attenuates airway inflammation and mucus production induced by cigarette smoke in rats

Cited by 49 publications

References 28 publications

Assay of lapatinib in murine models of cigarette smoke carcinogenesis

Assay of lapatinib in murine models of cigarette smoke carcinogenesis

Silymarin Attenuates Airway Inflammation Induced by Cigarette Smoke in Mice

Cytosolic Phospholipase A2α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae Infection

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Cytosolic Phospholipase A₂α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae Infection