Ambroxol anti-inflammatory properties Commentary
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Published:
Sep 30, 2019
Keywords:
ambroxol, mucolytic agent, airway infections, inflammation
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Abstract
Ambroxol is a classic mucolytic agent with secretagogue effects utilized in lower airway infection (LRTI) treatment in children and adults. Research data suggests that in fact it is a multi-faced molecule with scavenger, anti-inflammatory, anti-adhesion and airway biofilm modifying properties. Moreover, it inhibits viral proliferation in infected airway epithelial cells. Ambroxol has well documented efficacy and an excellent safety profile proved in many clinical research trials and long years in LRTI treatment.
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How to Cite
Pawliczak , R. (2019). Ambroxol anti-inflammatory properties. Medycyna Faktow (J EBM), 12(3(44), 276-280. https://doi.org/10.24292/01.MF.0319.16
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References
1. Beeh K.M., Beier J., Esperester A., Paul L.D.: Antiinflammatory properties of ambroxol. Eur. J. Med. Res. 2008; 13(12): 557-562.
2. Lampinen M., Rak S., Venge P.: The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung. Clin. Exp. Allergy 1999; 29(3): 314-322.
3. Su X., Wang L., Song Y., Bai C.: Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide. Intensive Care Med. 2004; 30(1): 133-140.
4. Lee C.S., Jang Y.Y., Han E.S.: Depressant effects of ambroxol on lipopolysaccharide- or fMLP-stimulated free radical production and granule enzyme release by alveolar macrophages. Pulm. Pharmacol. Ther. 1999; 12(5): 275-284.
5. Lee C.S., Jang Y.Y., Song J.S. et al.: Ambroxol inhibits peroxynitrite-induced damage of alpha1-antiproteinase and free radical production in activated phagocytic cells. Pharmacol. Toxicol. 2002; 91(3): 140-149.
6. Seifart C., Clostermann U., Seifart U. et al.: Cell-specific modulation of surfactant proteins by ambroxol treatment. Toxicol. Appl. Pharmacol. 2005; 203(1): 27-35.
7. Yang B., Yao D.F., Ohuchi M. et al.: Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels. Eur. Respir. J. 2002; 19(5): 952-958.
8. Poole P.J., Black P.N.: Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. BMJ 2001; 322(7297): 1271-1274.
9. Schutz A., Gund H.J., Pschorn U. et al.: Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore throat. Clinical proof of concept. Arzneimittelforschung 2002; 52(3): 194-199.
10. Fischer J., Pschorn U., Vix J.M. et al.: Efficacy and tolerability of ambroxol hydrochloride lozenges in sore throat. Randomised, double-blind, placebo- controlled trials regarding the local anaesthetic properties. Arzneimittelforschung 2002; 52(4): 256-263.
11. Paleari D., Rossi G.A., Nicolini G., Olivieri D.: Ambroxol: a multifaceted molecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin. Drug Discov. 2011; 6(11): 1203-1214.
12. Disse B.G., Ziegler H.W.: Pharmacodynamic mechanism and therapeutic activity of ambroxol in animal experiments. Respiration 1987; 51(supl. 1): 15-22.
13. Hull J.D., Lyon R.A.: In vitro pharmacology of ambroxol: Potential serotonergic sites of action. Life Sci. 2018; 197: 67-72.
14. de Mey C., Koelsch S., Richter E. et al.: Efficacy and Safety of Ambroxol Lozenges in the Treatment of Acute Uncomplicated Sore Throat – a Pooled Analysis. Drug Res. (Stuttg) 2016; 66(7): 384-392.
15. de Mey C., Patel J., Lakha D.R. et al.: Efficacy and Safety of an Oral Ambroxol Spray in the Treatment of Acute Uncomplicated Sore Throat. Drug Res. (Stuttg) 2015; 65(12): 658-667.
16. Malerba M., Ragnoli B.: Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin. Drug Metab. Toxicol. 2008; 4(8): 1119-1129.
17. Ge L.T., Liu Y.N., Lin X.X. et al.: Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway. Int. Immunopharmacol. 2016; 33: 90-98.
18. Gillissen A., Bartling A., Schoen S., Schultze-Werninghaus G.: Antioxidant function of ambroxol in mononuclear and polymorphonuclear cells in vitro. Lung 1997; 175(4): 235-242.
19. Gillissen A., Schärling B., Jaworska M. et al.: Oxidant scavenger function of ambroxol in vitro: a comparison with N-acetylcysteine. Res. Exp. Med. (Berl.) 1997; 196(6): 389-398.
20. Gupta P.R.: Ambroxol – Resurgence of an old molecule as an anti-inflammatory agent in chronic obstructive airway diseases. Lung India 2010; 27(2): 46-48.
21. Lapenna D., de Gioia S., Ciofani G., Cuccurullo F.: Ambroxol is a scavenger of hypochlorous acid and monochloramine. Pharmacology 1994; 49(2): 132-135.
22. Nowak D., Antczak A., Król M. et al.: Antioxidant properties of Ambroxol. Free Radic. Biol. Med. 1994; 16(4): 517-522.
23. Stockley R.A., Shaw J., Burnett D.: Effect of ambroxol of neutrophil chemotaxis in vitro. Agents Actions 1988; 24(3-4): 292-296.
24. Bianchi M., Mantovani A., Erroi A. et al.: Ambroxol inhibits interleukin 1 and tumor necrosis factor production in human mononuclear cells. Agents Actions 1990; 31(3-4): 275-279.
25. Gibbs B.F.: Differential modulation of IgE-dependent activation of human basophils by ambroxol and related secretolytic analogues. Int. J. Immunopathol. Pharmacol. 2009; 22(4): 919-927.
26. Gao X., Huang Y., Han Y. et al.: The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats. Arch. Med. Sci. 2011; 7(3): 405-413.
27. Lu Q., Yu J., Yang X. et al.: Ambroxol interferes with Pseudomonas aeruginosa quorum sensing. Int. J. Antimicrob. Agents 2010; 36(3): 211-215.
28. Stetinova V., Smetanová L., Kholová D. et al.: Transepithelial transport of ambroxol hydrochloride across human intestinal Caco-2 cell monolayers. Gen. Physiol. Biophys. 2009; 28(3): 309-315.
29. Zhang Y., Fu Y., Yu J. et al.: Synergy of ambroxol with vancomycin in elimination of catheter-related Staphylococcus epidermidis biofilm in vitro and in vivo. J. Infect. Chemother. 2015; 21(11): 808-815.
30. Nobata K., Fujimura M., Ishiura Y. et al.: Ambroxol for the prevention of acute upper respiratory disease. Clin. Exp. Med. 2006; 6(2): 79-83.
31. Cataldi M., Sblendorio V., Leo A., Piazza O.: Biofilm-dependent airway infections: a role for ambroxol? Pulm. Pharmacol. Ther. 2014; 28(2): 98-108.
32. Cazan D., Klimek L., Sperl A. et al.: Safety of ambroxol in the treatment of airway diseases in adult patients. Expert. Opin. Drug Saf. 2018; 17(12): 1211-1224.
33. Kong Q., Du X., Huang S. et al.: In vitro effects of ambroxol on Cryptococcus adherence, planktonic cells, and biofilms. APMIS 2017; 125(7): 634-640.
34. Li F., Wang W., Hu L. et al.: Effect of ambroxol on pneumonia caused by Pseudomonas aeruginosa with biofilm formation in an endotracheal intubation rat model. Chemotherapy 2011; 57(2): 173-180.
35. Wang W., Yu J., He Y. et al.: Ambroxol inhibits mucoid conversion of Pseudomonas aeruginosa and contributes to the bactericidal activity of ciprofloxacin against mucoid P. aeruginosa biofilms. APMIS 2016; 124(7): 611-618.
36. Olivieri D., Zavattini G., Tomasini G. et al.: Ambroxol for the prevention of chronic bronchitis exacerbations: long-term multicenter trial. Protective effect of ambroxol against winter semester exacerbations: a double-blind study versus placebo. Respiration 1987; 51(supl. 1): 42-51.
37. Leffler A., Reckzeh J., Nau C.: Block of sensory neuronal Na+ channels by the secreolytic ambroxol is associated with an interaction with local anesthetic binding sites. Eur. J. Pharmacol. 2010; 630(1-3): 19-28.
38. Deretic V., Timmins G.S.: Enhancement of lung levels of antibiotics by ambroxol and bromhexine. Expert. Opin. Drug Metab. Toxicol. 2019; 15(3): 213-218.
39. Gene R., Poderoso J.J., Corazza C. et al.: Influence of ambroxol on amoxicillin levels in bronchoalveolar lavage fluid. Arzneimittelforschung 1987; 37(8): 967-968.
40. Peralta J., Poderoso J.J., Corazza C. et al.: Ambroxol plus amoxicillin in the treatment of exacerbations of chronic bronchitis. Arzneimittelforschung 1987; 37(8): 969-971.
41. Spatola J., Poderoso J.J., Wiemeyer J.C. et al.: Influence of ambroxol on lung tissue penetration of amoxicillin. Arzneimittelforschung 1987; 37(8): 965-966.
42. Villacampa J., Alcántar F., Rodríguez J.M. et al.: Pharmacokinetic properties of single-dose loratadine and ambroxol alone and combined in tablet formulations in healthy men. Clin. Ther. 2003; 25(8): 2225-2232.
43. Charakterystyka leku Mucosolvan Syrop; 05.2017.
2. Lampinen M., Rak S., Venge P.: The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung. Clin. Exp. Allergy 1999; 29(3): 314-322.
3. Su X., Wang L., Song Y., Bai C.: Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide. Intensive Care Med. 2004; 30(1): 133-140.
4. Lee C.S., Jang Y.Y., Han E.S.: Depressant effects of ambroxol on lipopolysaccharide- or fMLP-stimulated free radical production and granule enzyme release by alveolar macrophages. Pulm. Pharmacol. Ther. 1999; 12(5): 275-284.
5. Lee C.S., Jang Y.Y., Song J.S. et al.: Ambroxol inhibits peroxynitrite-induced damage of alpha1-antiproteinase and free radical production in activated phagocytic cells. Pharmacol. Toxicol. 2002; 91(3): 140-149.
6. Seifart C., Clostermann U., Seifart U. et al.: Cell-specific modulation of surfactant proteins by ambroxol treatment. Toxicol. Appl. Pharmacol. 2005; 203(1): 27-35.
7. Yang B., Yao D.F., Ohuchi M. et al.: Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels. Eur. Respir. J. 2002; 19(5): 952-958.
8. Poole P.J., Black P.N.: Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. BMJ 2001; 322(7297): 1271-1274.
9. Schutz A., Gund H.J., Pschorn U. et al.: Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore throat. Clinical proof of concept. Arzneimittelforschung 2002; 52(3): 194-199.
10. Fischer J., Pschorn U., Vix J.M. et al.: Efficacy and tolerability of ambroxol hydrochloride lozenges in sore throat. Randomised, double-blind, placebo- controlled trials regarding the local anaesthetic properties. Arzneimittelforschung 2002; 52(4): 256-263.
11. Paleari D., Rossi G.A., Nicolini G., Olivieri D.: Ambroxol: a multifaceted molecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin. Drug Discov. 2011; 6(11): 1203-1214.
12. Disse B.G., Ziegler H.W.: Pharmacodynamic mechanism and therapeutic activity of ambroxol in animal experiments. Respiration 1987; 51(supl. 1): 15-22.
13. Hull J.D., Lyon R.A.: In vitro pharmacology of ambroxol: Potential serotonergic sites of action. Life Sci. 2018; 197: 67-72.
14. de Mey C., Koelsch S., Richter E. et al.: Efficacy and Safety of Ambroxol Lozenges in the Treatment of Acute Uncomplicated Sore Throat – a Pooled Analysis. Drug Res. (Stuttg) 2016; 66(7): 384-392.
15. de Mey C., Patel J., Lakha D.R. et al.: Efficacy and Safety of an Oral Ambroxol Spray in the Treatment of Acute Uncomplicated Sore Throat. Drug Res. (Stuttg) 2015; 65(12): 658-667.
16. Malerba M., Ragnoli B.: Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin. Drug Metab. Toxicol. 2008; 4(8): 1119-1129.
17. Ge L.T., Liu Y.N., Lin X.X. et al.: Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway. Int. Immunopharmacol. 2016; 33: 90-98.
18. Gillissen A., Bartling A., Schoen S., Schultze-Werninghaus G.: Antioxidant function of ambroxol in mononuclear and polymorphonuclear cells in vitro. Lung 1997; 175(4): 235-242.
19. Gillissen A., Schärling B., Jaworska M. et al.: Oxidant scavenger function of ambroxol in vitro: a comparison with N-acetylcysteine. Res. Exp. Med. (Berl.) 1997; 196(6): 389-398.
20. Gupta P.R.: Ambroxol – Resurgence of an old molecule as an anti-inflammatory agent in chronic obstructive airway diseases. Lung India 2010; 27(2): 46-48.
21. Lapenna D., de Gioia S., Ciofani G., Cuccurullo F.: Ambroxol is a scavenger of hypochlorous acid and monochloramine. Pharmacology 1994; 49(2): 132-135.
22. Nowak D., Antczak A., Król M. et al.: Antioxidant properties of Ambroxol. Free Radic. Biol. Med. 1994; 16(4): 517-522.
23. Stockley R.A., Shaw J., Burnett D.: Effect of ambroxol of neutrophil chemotaxis in vitro. Agents Actions 1988; 24(3-4): 292-296.
24. Bianchi M., Mantovani A., Erroi A. et al.: Ambroxol inhibits interleukin 1 and tumor necrosis factor production in human mononuclear cells. Agents Actions 1990; 31(3-4): 275-279.
25. Gibbs B.F.: Differential modulation of IgE-dependent activation of human basophils by ambroxol and related secretolytic analogues. Int. J. Immunopathol. Pharmacol. 2009; 22(4): 919-927.
26. Gao X., Huang Y., Han Y. et al.: The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats. Arch. Med. Sci. 2011; 7(3): 405-413.
27. Lu Q., Yu J., Yang X. et al.: Ambroxol interferes with Pseudomonas aeruginosa quorum sensing. Int. J. Antimicrob. Agents 2010; 36(3): 211-215.
28. Stetinova V., Smetanová L., Kholová D. et al.: Transepithelial transport of ambroxol hydrochloride across human intestinal Caco-2 cell monolayers. Gen. Physiol. Biophys. 2009; 28(3): 309-315.
29. Zhang Y., Fu Y., Yu J. et al.: Synergy of ambroxol with vancomycin in elimination of catheter-related Staphylococcus epidermidis biofilm in vitro and in vivo. J. Infect. Chemother. 2015; 21(11): 808-815.
30. Nobata K., Fujimura M., Ishiura Y. et al.: Ambroxol for the prevention of acute upper respiratory disease. Clin. Exp. Med. 2006; 6(2): 79-83.
31. Cataldi M., Sblendorio V., Leo A., Piazza O.: Biofilm-dependent airway infections: a role for ambroxol? Pulm. Pharmacol. Ther. 2014; 28(2): 98-108.
32. Cazan D., Klimek L., Sperl A. et al.: Safety of ambroxol in the treatment of airway diseases in adult patients. Expert. Opin. Drug Saf. 2018; 17(12): 1211-1224.
33. Kong Q., Du X., Huang S. et al.: In vitro effects of ambroxol on Cryptococcus adherence, planktonic cells, and biofilms. APMIS 2017; 125(7): 634-640.
34. Li F., Wang W., Hu L. et al.: Effect of ambroxol on pneumonia caused by Pseudomonas aeruginosa with biofilm formation in an endotracheal intubation rat model. Chemotherapy 2011; 57(2): 173-180.
35. Wang W., Yu J., He Y. et al.: Ambroxol inhibits mucoid conversion of Pseudomonas aeruginosa and contributes to the bactericidal activity of ciprofloxacin against mucoid P. aeruginosa biofilms. APMIS 2016; 124(7): 611-618.
36. Olivieri D., Zavattini G., Tomasini G. et al.: Ambroxol for the prevention of chronic bronchitis exacerbations: long-term multicenter trial. Protective effect of ambroxol against winter semester exacerbations: a double-blind study versus placebo. Respiration 1987; 51(supl. 1): 42-51.
37. Leffler A., Reckzeh J., Nau C.: Block of sensory neuronal Na+ channels by the secreolytic ambroxol is associated with an interaction with local anesthetic binding sites. Eur. J. Pharmacol. 2010; 630(1-3): 19-28.
38. Deretic V., Timmins G.S.: Enhancement of lung levels of antibiotics by ambroxol and bromhexine. Expert. Opin. Drug Metab. Toxicol. 2019; 15(3): 213-218.
39. Gene R., Poderoso J.J., Corazza C. et al.: Influence of ambroxol on amoxicillin levels in bronchoalveolar lavage fluid. Arzneimittelforschung 1987; 37(8): 967-968.
40. Peralta J., Poderoso J.J., Corazza C. et al.: Ambroxol plus amoxicillin in the treatment of exacerbations of chronic bronchitis. Arzneimittelforschung 1987; 37(8): 969-971.
41. Spatola J., Poderoso J.J., Wiemeyer J.C. et al.: Influence of ambroxol on lung tissue penetration of amoxicillin. Arzneimittelforschung 1987; 37(8): 965-966.
42. Villacampa J., Alcántar F., Rodríguez J.M. et al.: Pharmacokinetic properties of single-dose loratadine and ambroxol alone and combined in tablet formulations in healthy men. Clin. Ther. 2003; 25(8): 2225-2232.
43. Charakterystyka leku Mucosolvan Syrop; 05.2017.