Effects of Ambroxol on Spontaneous or Stimulated Generation of Reactive Oxygen Species by Bronchoalveolar Lavage Cells Harvested from Patients With or Without Chronic Obstructive Pulmonary Diseases

Teramoto, Shinji; Suzuki, Masashi; Ohga, Eijiro; Ishii, Takeo; Matsui, Hirotoshi; Matsuse, Takeshi; Ouchi, Yasuyoshi

doi:10.1159/000028313

Cited by 13 publications

(5 citation statements)

References 24 publications

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“…In the animal studies, treatment with anti-oxidant reagents or genetic manipulation, the over-expression of Cu/Zn superoxide dismutase or deficiency of nuclear erythroid 2 p45-related factor 2, a transcription factor regulating many antioxidant genes, were shown to be protective in the airways ( 37 38 39 ). Ambroxol has been shown to have anti-oxidant properties and reduce oxidant production from inflammatory cells In vitro , such as polymorphonuclear cells, alveolar macrophages, or human bronchial epithelial cells ( 16 40 41 42 ), and inhibited AHR induced by ozone in dogs ( 43 ). In the present study, we demonstrated that ambroxol treatment begun after OVA challenge of sensitized mice decreased the levels of protein carbonyls in BAL fluid, a biomarker of oxidative stress ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

et al. 2016

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Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

et al. 2016

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“…Both drugs are also approved for veterinary administration and commonly marketed as tablets, granules, syrups, capsules, drops and injections for use in the therapy of pulmonary diseases, chronic bronchitis or pneumonia. Other clinically significant properties of ambroxol are radical scavenger activity [1,2], in vivo inhibition of doxorubidn-induced lipid peroxidation [2] and blocking generation of reactive oxygen species in placenta [3] and bronchoalveolar cells [4]. It also prevents Helicobacter pylori associated gastric carcinogenesis [1] and has valuable antiinflammatory activity by inhibiting the release of inflammatory mediators from human lenkocytes and mast cells [5].…”

Section: Introductionmentioning

confidence: 99%

Macrocycleversus podant-type neutral ionophore in potentiometric detection of mucolytic agents following separation by various HPLC modes

2003

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SummaryPotentiometrTc detection of lipophTlic drugs such as clenbuterol, ambroxol and bromhexine in standard bore cyano and narrow bore hybrid, reversed phase HPLC systems was developed to enable specific determination of these mucolytic agents in some marketed oral formula tions. The macrocycle and podant type, neutral ionophores, respectively: hexaks(2,3,64ri O octyl) ~ cyclodextrin (CDX) and N,N,N',N'4etracyclohexyl oxybis(o phenyleneoxy)diaceta mide flOPA), were used to construct PVC based, liquid membrane electrodes. In addic aqu eous-acetonTtrile, mobTle phases both Tonophores Tmproved the sensitTvTty of these electrodes for mucolytic agents when compared to single-wavelength UV detedTon -as well as wTth the ionophore-free based electrode. In the case of bromhexTne, TndTcating highest ITpophilTdty (IogP6.40), detection limits of 2.6 x ]0 lo and 1.4 x ]0 l~ (injected concentration) were achieved with a signal-to-noTse (S/N) ratio of 3 wTth the TOPA-modified, liquid membrane electrode in the varTous RP-HPLC systems. The results of procedures validated for sTmultaneous potentiometrTc determination of clenbuterol and ambroxol Tn tablets marketed in di[ferent countries are also presented.

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“…Ambroxol and beclomethasone alone showed an inhibitory effect on LPS-induced IL-8 and MPO release and 3-NT formation in BEAS-2B cells cocultured with neutrophils, and the combination of the two drugs enhanced their effect on IL-8 and 3-NT. In other studies, ambroxol or beclomethasone were able to inhibit nitrosative stress [8,13,22], and ambroxol alone showed a great antioxidant activity, operating as scavenger of HClO and OH, and also revealed the capacity to decompose H 2 O 2 in an in vitro study [12], but the combination has not previously been investigated in this context.…”

Section: Discussionmentioning

confidence: 99%

“…Ambroxol has been shown to prevent generation of reactive oxygen species by broncho-alveolar lavage cells from COPD patients [13] suggesting that it may be useful in the management of COPD [14,15]. Moreover, ambroxol's antioxidant properties may be of clinical benefit in virus-induced infections.…”

Section: Introductionmentioning

confidence: 99%

Effect of Ambroxol and Beclomethasone on Lipopolysaccharide-Induced Nitrosative Stress in Bronchial Epithelial Cells

Ricciardolo¹,

Sorbello²,

Benedetto³

et al. 2015

Respiration

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Background: Nitrosative stress is involved in different airway diseases. Lipopolysaccharide (LPS) induces neutrophil-related cytokine release and nitrosative stress in human bronchial epithelial (BEAS-2B) cells alone or with human polymorphonuclear neutrophils (PMNs). Ambroxol protects against oxidative stress, and beclomethasone dipropionate is an anti-inflammatory drug. Objectives: We evaluated the ability of ambroxol and/or beclomethasone dipropionate to inhibit LPS-induced expression/release of RANTES, IL-8, inducible NO synthase (iNOS), myeloperoxidase (MPO) and 3-nitrotyrosine (3-NT: nitrosative stress biomarker) in BEAS-2B ± PMNs stimulated with LPS (1 μg/ml). Methods: The effect of ambroxol and/or beclomethasone dipropionate on IL-8, RANTES and iNOS levels was assessed by Western blot analysis; IL-8, MPO and 3-NT levels were measured by ELISA. Cell viability was assessed by the trypan blue exclusion test. Results: In BEAS-2B alone, LPS (at 12 h) increased RANTES/iNOS expression and IL-8 levels (p < 0.001). Ambroxol suppressed LPS-induced RANTES expression and IL-8 release (p < 0.001), whilst inhibiting iNOS expression (p < 0.05). Beclomethasone dipropionate had no effect on RANTES but halved iNOS expression and IL-8 release. Coculture of BEAS-2B with PMNs stimulated IL-8, MPO and 3-NT production (p < 0.001), potentiated by LPS (p < 0.001). Ambroxol and beclomethasone dipropionate inhibited LPS-stimulated IL-8, MPO and 3-NT release (p < 0.05). Ambroxol/beclomethasone dipropionate combination potentiated the inhibition of IL-8 and 3-NT production in BEAS-2B with PMNs (p < 0.05 and p < 0.01, respectively). Ambroxol and/or beclomethasone dipropionate inhibited nitrosative stress and the release of neutrophilic inflammatory products in vitro. Conclusion: The additive effect of ambroxol and beclomethasone dipropionate on IL-8 and 3-NT inhibition suggests new therapeutic options in the treatment of neutrophil-related respiratory diseases such as chronic obstructive pulmonary disease and respiratory infections.

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Effects of Ambroxol on Spontaneous or Stimulated Generation of Reactive Oxygen Species by Bronchoalveolar Lavage Cells Harvested from Patients With or Without Chronic Obstructive Pulmonary Diseases

Cited by 13 publications

References 24 publications

Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

Macrocycleversus podant-type neutral ionophore in potentiometric detection of mucolytic agents following separation by various HPLC modes

Effect of Ambroxol and Beclomethasone on Lipopolysaccharide-Induced Nitrosative Stress in Bronchial Epithelial Cells

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