Mucoregulator, antioxidant, pneumoprotector — a modern conception of the role of acetylcysteine in treatment of respiratory system diseases | Ukrainian Medical Journal

Nikolaenko V.B.

Main
Publications
Mucoregulator, antioxidant, pneumoprotector — a modern conception of the role of acetylcysteine in treatment of respiratory system diseases

Mucoregulator, antioxidant, pneumoprotector — a modern conception of the role of acetylcysteine in treatment of respiratory system diseases

February 7, 2019

920

Allergology and Pulmonology

Infectious diseases

Pediatrics

Therapy, General practice

Phthisiology

Nikolaenko V.B.

Specialities :

Allergology and Pulmonology

Infectious diseases

Pediatrics

Therapy, General practice

Phthisiology

Resume

Accumulated over the past decades data of experimental studies and clinical trials significantly expanded the understanding of mechanisms of N-acetylcysteine positive action in patients with pathology of respiratory system. N-acetylcysteine has been reported to have pleiotropic effect, closely connected with antioxidant action: direct — that is realized by thiol group, and indirect — due to increasing of intracellular glutathione levels, thus regulating of intracellular redox status. Moreover, N-acetylcysteine has muco-regulatory, anti-inflammatory, pneumo-protective, anti-infective action. In acute and chronic respiratory system diseases with thick and purulence sputum N-acetylcysteine benefits in positive dynamics of clinical manifestation, attenuates the lung injury and improves lung function, decreases the frequency of acute exacerbations as well as improves the physical performance and quality of life. Good tolerability and low incidence of adverse reactions, even observed during the long-term administration in high doses, can be explained by the antitoxic, nephro- and hepatoprotective effects and special pharmacokinetic characteristics of N-acetylcysteine.

Published: 07.02.2019

References:

Belyaeva L.E., Shebeko V.I., Solodkov A.P. (2008) Redoks-zavisimyie mehanizmyi deystviya N-atsetiltsisteina. Vest. Vitebskogo gos. med. univer., 7(4): 5–15.
Kompendium — lekarstvennyie preparatyi (2017) EVKABAL^® SASHE (EUCABAL^® SACHET) (https://compendium.com.ua/info/339085/evkabal-supsup-sashe).
Ministerstvo okhorony zdorovia Ukrainy (2018) Nakaz Ministerstva okhorony zdorovia Ukrainy vid 02.04.2018 r. № 599 «Pro zatverdzhennia Pereliku likarskykh zasobiv, dozvolenykh do zastosuvannia v Ukraini, yaki vidpuskaiutsia bez retseptiv z aptek ta yikh strukturnykh pidrozdiliv» (https://zakon.rada.gov.ua/laws/show/z0494-18).
Soodaeva S.K., Nikitina L.Yu., Klimanov I.A. (2015) Mehanizmyi razvitiya oksidativnogo stressa pod vozdeystviem aeropollyutantov okruzhayuschey sredyi: potentsial sredstv antioksidantnoy zaschityi. Pulmonologiya, 25(6): 736–742.
Amaral E.P., Conceição E.L., Costa D.L. et al. (2016) N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions. BMC Microbiol., 16(1): 251.
Backer J.D., Vos W., Holsbeke C.V. et al. (2013) Double blind, randomized, two-way crossover, pilot study to assess the effect of high dose N-acetylcysteine on airway geometry, inflammation and oxidative stress in copd patients using functional respiratory imaging. Am. J. Resp. Crit. Care Med., 187: A2447.
Behr J., Demedts M., Buhl R. et al.; IFIGENIA study group (2009) Lung function in idiopathic pulmonary fibrosis — extended analyses of the IFIGENIA trial. Respir. Res., 10: 101.
Bustos T.C., Garigliany M. (2016) N-acetylcysteine: an old drug with variable anti-influenza properties. J. Controvers. Biomed. Res., 2(1): 1–8.
Cai S., Chen P., Zhang C. et al. (2009) Oral N-acetylcysteine attenuates pulmonary emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats. Respirology, 14(3): 354–359.
Calzetta L., Matera M.G., Rogliani P., Cazzola M. (2018) Multifaceted activity of N-acetyl-l-cysteine in chronic obstructive pulmonary disease. Expert Rev. Respir. Med., 12(8): 693–708.
Chalumeau M., Duijvestijn Y.C. (2013) Acetylcysteine and carbocysteine for acute upper and lower respiratory tract infections in paediatric patients without chronic broncho-pulmonary disease. Cochrane Database Syst. Rev., 5: CD003124.
Circu M.L., Aw T.Y. (2012) Glutathione and modulation of cell apoptosis. Biochim. Biophys. Acta., 1823(10): 1767–1777.
Conrad C., Lymp J., Thompson V. et al. (2015) Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial. J. Cyst. Fibros., 14(2): 219–227.
Criner G.J., Bourbeau J., Diekemper R.L. et al. (2015) Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest, 147(4): 894–942.
Dauletbaev N., Fischer P., Aulbach B. et al. (2009) A phase II study on safety and efficacy of high-dose N-acetylcysteine in patients with cystic fibrosis. Eur. J. Med. Res., 14(8): 352–358.
De Caro L., Ghizzi A., Costa R. et al. (1989) Pharmacokinetics and bioavailability of oral acetylcysteine in healthy volunteers. Arzneimittelforschung, 39(3): 382–386.
Decramer M., Rutten-van Mölken M., Dekhuijzen P.N. et al. (2005) Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet, 365(9470): 1552–1560.
Dekhuijzen P.N., van Beurden W.J. (2006) The role for N-acetylcysteine in the management of COPD. Int. J. Chron. Obstruct. Pulmon. Dis., 1(2): 99–106.
Dinicola S., De Grazia S., Carlomagno G., Pintucci J.P. (2014) N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur. Rev. Med. Pharmacol. Sci., 18(19): 2942–2948.
DrugBank (2018) Acetylcysteine (https://www.drugbank.ca/drugs/DB06151).
Eklund A., Eriksson O., Håkansson L. et al. (1988) Oral N-acetylcysteine reduces selected humoral markers of inflammatory cell activity in BAL fluid from healthy smokers: correlation to effects on cellular variables. Eur. Respir. J., 1(9): 832–838.
Garozzo A., Tempera G., Ungheri D. et al. (2007) N-acetylcysteine synergizes with oseltamivir in protecting mice from lethal influenza infection. Int. J. Immunopathol. Pharmacol., 20(2): 349–354.
Geiler J., Michaelis M., Naczk P. et al. (2010) N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochem. Pharmacol., 79(3): 413–420.
Global Initiative for Chronic Obstructive Lung Disease (2018) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2019 Report (https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf).
Hui D.S., Lee N., Chan P.K., Beigel J.H. (2018) The role of adjuvant immunomodulatory agents for treatment of severe influenza. Antiviral. Res., 150: 202–216.
Landini G., Di Maggio T., Sergio F. et al. (2016) Effect of high N-acetylcysteine concentrations on antibiotic activity against a large collection of respiratory pathogens. Antimicrob. Agents Chemother., 60(12): 7513–7517.
Mårtensson J., Gustafsson J., Larsson A. (1989) A therapeutic trial with N-acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria). J. Inherit. Metab. Dis., 12(2): 120–130.
Martindale J.L., Holbrook N.J. (2002) Cellular response to oxidative stress: signaling for suicide and survival. J. Cell. Physiol., 192(1): 1–15.
Moon J.H., Choi Y.S., Lee H.W. et al. (2016) Antibacterial effects of N-acetylcysteine against endodontic pathogens. J. Microbiol., 54(4): 322–329.
NICE (2018) Chronic obstructive pulmonary disease in over 16s: diagnosis and management (https://www.nice.org.uk/guidance/ng115/chapter/Recommendations#lung-surgery-and-lung-volume-reduction-procedures-Oral-mucolytic%20therapy).
Oka S., Kamata H., Kamata K. et al. (2000) N-acetylcysteine suppresses TNF-induced NF-kappaB activation through inhibition of IkappaB kinases. FEBS Lett, 472(2–3): 196–202.
Onk D., Özçelik F., Onk O.A. et al. (2018) Assessment of renal and hepatic tissue-protective effects of N-acetylcysteine via ammonia metabolism: a prospective randomized study. Med. Sci. Monit., 24: 1540–1546.
Parasassi T., Brunelli R., Costa G. et al. (2010) Thiol redox transitions in cell signaling: a lesson from N-acetylcysteine. Sci. World J., 10: 1192–1202.
Pei Y., Liu H., Yang Y. et al. (2018) Biological activities and potential oral applications of N-acetylcysteine: progress and prospects. Oxid. Med. Cell Longev., 2018: 2835787.
Pizzorno J.E., Katzinger J.J. (2012) Glutathione: physiological and clinical relevance. J. Rest. Med., 1(1): 24–37.
Poole P., Chong J., Cates C.J. (2015) Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst. Rev., 7: CD001287.
Riise G.C., Qvarfordt I., Larsson S. et al. (2000) Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro. Respiration, 67(5): 552–558.
Roy R., Tiwari M., Donelli G., Tiwari V. (2018) Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action. Virulence, 9(1): 522–554.
Sadowska A.M. (2012) N-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary disease. Ther. Adv. Respir. Dis., 6(3): 127–135.
Stav D., Raz M. (2009) Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study. Chest, 136(2): 381–386.
Stey C., Steurer J., Bachmann S. et al. (2000) The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur. Respir. J., 16(2): 253–262.
Teskey G., Cao R., Islamoglu H. et al. (2018) The Synergistic effects of the glutathione precursor, NAC and first-line antibiotics in the granulomatous response against Mycobacterium tuberculosis. Front. Immunol., 9: 2069.
Tirouvanziam R., Conrad C.K., Bottiglieri T. et al. (2006) High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc. Natl. Acad. Sci. USA, 103(12): 4628–4633.
Tse H.N., Raiteri L., Wong K.Y. et al. (2013) High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study. Chest, 144(1): 106–118.
Valdivieso Á.G., Dugour A.V., Sotomayor V. et al. (2018) N-acetyl cysteine reverts the proinflammatory state induced by cigarette smoke extract in lung Calu-3 cells. Redox Biol., 16: 294–302.
WHO (2017) WHO Model List of Essential Medicines (http://apps.who.int/iris/bitstream/handle/10665/273826/EML-20-eng.pdf).
Yan X., Song Y., Shen C. et al. (2017) Mucoactive and antioxidant medicines for COPD: consensus of a group of Chinese pulmonary physicians. Int. J. Chron. Obstruct. Pulmon. Dis., 12: 803–812.
Zafarullah M., Li W.Q., Sylvester J., Ahmad M. (2003) Molecular mechanisms of N-acetylcysteine actions. Cell Mol. Life Sci., 60(1): 6–20.
Zhang Q., Ju Y., Ma Y., Wang T. (2018) N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: A randomized controlled trial. Medicine (Baltimore), 97(45): e13087.
Zheng J.P., Wen F.Q., Bai C.X. et al.; PANTHEON study group (2014) Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir. Med., 2(3): 187–194.
Zuin R., Palamidese A., Negrin R. et al. (2005) High-dose N-acetylcysteine in patients with exacerbations of chronic obstructive pulmonary disease. Clin. Drug Investig., 25(6): 401–408.