The antioxidative activity of the mucoregulatory agents: Ambroxol, bromhexine and N-acetyl-L-cysteine. A pulse radiolysis study

Felix, Klaus; Pairet, M.; Zimmermann, Rainer

doi:10.1016/0024-3205(96)00431-6

Cited by 46 publications

(25 citation statements)

References 14 publications

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“…Ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexane hydrochloride] (AMB) is a bromhexin metabolite. Although the functional mechanism of AMB is still unknown, AMB is reported to stimulate the synthesis and secretion of surfactant in type 2 alveolar epithelium [22]and to scavenge oxidants [23]. Both agents have been widely used as mucolytic drugs in the treatment of lung diseases, despite the differences between their chemical structures.…”

Section: Introductionmentioning

confidence: 99%

“…Both agents have been widely used as mucolytic drugs in the treatment of lung diseases, despite the differences between their chemical structures. Recent studies have identified an antioxidative role for NAC and AMB in the treatment of pulmonary disorders [23, 24], but there have been no reports about the effect of these drugs on cytokine secretion from monocytes/macrophages. Thus, we examined the effects of NAC and AMB on the lipopolysaccharide (LPS) induced secretions of IL-12 and IL-10 and the balance of IL-12 and IL-10 secretions from human A-MFs.…”

Section: Introductionmentioning

confidence: 99%

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Effects of N-Acetylcysteine and Ambroxol on the Production of IL-12 and IL-10 in Human Alveolar Macrophages

et al. 2000

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Background: N-acetylcysteine (NAC) and ambroxol (AMB) have recently been proposed as possible therapeutic agents in the treatment of pulmonary disorders. IL-12 plays an important role in host resistance to infection and the development of Th-1 cells. In contrast, IL-10 is involved in anti-inflammatory and immunoregulatory mechanisms. Objective: We investigated the effects of NAC and AMB on secretions of IL-12 and IL-10 from human alveolar macrophages. Methods: Alveolar macrophages were obtained from 7 healthy nonsmokers by bronchoalveolar lavage. The cells were first incubated with either NAC or AMB for 2 h and then cultured in lipopolysaccharide (LPS) solution for 24 h. IL-12 and IL-10 secretions were measured by ELISA. Result: Both NAC and AMB enhanced LPS-induced secretion of IL-12. NAC also enhanced LPS-induced IL-10 secretion, while AMB did not. The ratio IL-12/IL-10 secretion was increased by AMB, but NAC did not affect it. Conclusions: The results suggest that NAC enhances inflammatory and immune responses and prevents excessive responses reciprocally, through keeping local balance of IL-12 and IL-10 production in alveolar macrophages at inflammatory sites of bacterial pneumonia. AMB appears to strengthen inflammatory responses and cell-mediated immunity, facilitating the development of Th-1 cells, through shifting the local balance to IL-12 dominance.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of N-Acetylcysteine and Ambroxol on the Production of IL-12 and IL-10 in Human Alveolar Macrophages

et al. 2000

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“…through Na' channels and CI-IHC0 3 -exchangers in human epithelial cell lines (26)(27), alongside its known antioxidant and free radical scavenging properties (28)(29). However, there is at present no clear evidence to show that these properties account for the mode of action of ambroxol on basophils.…”

Section: Brmentioning

confidence: 99%

Differential Modulation of IgE-Dependent Activation of Human Basophils by Ambroxol and Related Secretolytic Analogues

Gibbs

2009

Int J Immunopathol Pharmacol

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Ambroxol is a widely used secretolytic agent originally developed from vasicine, a natural alkaloid found in Adhatoda vasica, extracts of which have been used to treat bronchitis, asthma, and rheumatism. We previously reported that ambroxol inhibits IgE-dependent mediator secretion from human mast cells and basophils, key effector cells of allergic inflammation. Here, the mechanisms involved in the inhibitory properties of ambroxol were assessed in comparison to other secretolytic analogues (e.g, vasicine, bromhexine, sputolysin). The results show that, in comparison to ambroxol, which reduced IgE-dependent histamine release from basophils at 10 /lM-1 mM, the release of the amine was only moderately reduced by sputolysin and vasicine at 1 mM. In contrast, above 10 /lM, bromhexine was found to be toxic to basophils in vitro as evidenced by induction of histamine release and reduced cell viability. In contrast, the inhibitory actions of ambroxol at concentrations below 1 mM were not toxic and entirely reversible. Ambroxol was also more potent than either sputolysin or vasicine in attenuating basophil IL-4 and IL-13 secretions, whereas bromhexine-induced suppression of de novo cytokine synthesis was due to toxic effects. Additionally, ambroxol reduced IgE-dependent p38 MAPK phosphorylation in basophils, unlike bromhexine, sputolysin and vasicine. These results clearly show that ambroxol is both more potent and effective at inhibiting IgE-dependent basophil mediator release and p38 MAPK activity than the other secretolytic analogues employed. The therapeutic potential of ambroxol as an anti-allergic agent is further underlined by these data.

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“…In addition to the function of augmented mucociliary transport on airways, it has been suggested that ambroxol exhibits an antioxidant activity in vitro [11][12][13][14] and in vivo [15][16][17]. However, effects of ambroxol on generation of ROS by lung lavage cells have not been extensively determined in patients with COPD.…”

Section: Introductionmentioning

confidence: 99%

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

Teramoto¹,

Suzuki²,

Ohga³

et al. 1999

Pharmacology

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We examined the effects of ambroxol on spontaneous or stimulated generation of reactive oxygen species (ROS) by bronchoalveolar lavage (BAL) cells prepared from 6 patients with chronic obstructive pulmonary disease (COPD) and age-matched control subjects without COPD. The ROS produced by BAL cells were measured by the lucigenin-dependent chemiluminescence method. The application of ambroxol into culture media containing BAL cells inhibited spontaneous and stimulated generation of ROS by BAL cells harvested from COPD patients and control subjects in an ambroxol concentration-dependent manner. These results indicate that ambroxol may be a candidate agent for reducing oxidant stresses of airways in COPD.

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The antioxidative activity of the mucoregulatory agents: Ambroxol, bromhexine and N-acetyl-L-cysteine. A pulse radiolysis study

Cited by 46 publications

References 14 publications

Effects of N-Acetylcysteine and Ambroxol on the Production of IL-12 and IL-10 in Human Alveolar Macrophages

Effects of N-Acetylcysteine and Ambroxol on the Production of IL-12 and IL-10 in Human Alveolar Macrophages

Differential Modulation of IgE-Dependent Activation of Human Basophils by Ambroxol and Related Secretolytic Analogues

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

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