Abstract
Neonatal meconium aspiration syndrome (MAS) can be treated by exogenous surfactant (S). However, aspirated meconium initiates local inflammation and oxidation which may inactivate surfactant and reduce its action. This experimental study estimated whether combined use of surfactant and the antioxidant N-acetylcysteine (NAC) can enhance effectiveness of therapy. Meconium-instilled rabbits were non-treated (M), treated with monotherapies (M + S, M + NAC), combined therapy (M + S + NAC), or received saline instead of meconium (controls, C). Surfactant therapy consisted of two lung lavages (BAL) with diluted Curosurf (5 mg phospholipids/ml, 10 ml/kg) followed by undiluted Curosurf (100 mg phospholipids/kg). N-acetylcysteine (Acc Injekt, 10 mg/kg) was given intravenously in M + S + NAC group 10 min after surfactant therapy. Animals were oxygen-ventilated for additional 5 h. Then, differential white cell count in the blood (WBC) was determined. Left lung was saline-lavaged and differential cell count in BAL was determined. In right lung tissue, wet/dry weight ratio, oxidation markers (TBARS, 3NT) and interleukines (IL-2, IL-6, IL-13, and TNFα) using ELISA and RT-PCR were estimated. Combined S + NAC therapy significantly decreased W/D ratio, TBARS, 3NT, and IL, whereas the effect of monotherapies (either S or NAC) was less obvious. In conclusion, addition of NAC to surfactant treatment may enhance the therapeutic outcome in MAS.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Anderson P (2008) Post-transcriptional control of cytokine production. Nat Immunol 9:353–359
Bhatia M, Moochhala S (2004) Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 202:145–156
Castellheim A, Pharo A, Fung M, Saugstad OD, Mollnes TE (2005) Complement C5a is a key mediator of meconium-induced neutrophil activation. Pediatr Res 57:242–247
Craig S, Lopez A, Hoskin D, Markham F (2005) Meconium inhibits phagocytosis and stimulates respiratory burst in alveolar macrophages. Pediatr Res 57:813–818
Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Ciccolo A, Centorrino T, De Sarro A, Caputi AP (2001) Protective effects of n-acetylcysteine on lung injury and red blood cell modification induced by carrageenan in the rat. FASEB J 15:1187–1200
Dani C, Pratesi S (2013) Nitric oxide for the treatment of preterm infants with respiratory distress syndrome. Expert Opin Pharmacother 14:97–103
Dargaville PA, Mills JF, HeadleyBM CY, Coleman L, Loughnan PM, Morley CJ (2003) Therapeutic lung lavage in the piglet model of meconium aspiration syndrome. Am J Respir Crit Care Med 168:456–463
De Beaufort AJ, Bakker AC, van Tol MJ, Poorthuis BJ, Schrama AJ, Berger HM (2003) Meconium is a source of pro-inflammatory substances and can induce cytokine production in cultured A549 epithelial cells. Pediatr Res 54:491–495
Dodd S, Dean O, Copolov DL, Malhi GS, Berk M (2008) N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther 8:1955–1962
Grommes J, Soehnlein O (2011) Contribution of neutrophils to acute lung injury. Mol Med 17:293–307
Kääpä P, Soukka H (2008) Phospholipase A2 in meconium-induced lung injury. J Perinatol 28:120–122
Kattan J, González A, Becker P, Faunes M, Estay A, Toso P, Urzúa S, Castillo A, Fabres J (2013) Survival of newborn infants with severe respiratory failure before and after establishing an extracorporeal membrane oxygenation program. Pediatr Crit Care Med 14:876–883
Langley SC, Kelly FJ (1993) N-acetylcysteine ameliorates hyperoxic lung injury in the preterm guinea pig. Biochem Pharmacol 45:841–846
Mikolka P, Mokra D, Kopincova J, Tomciková-Mikusiakova L, Calkovska A (2013) Budesonide added to modified porcine surfactant Curosurf may additionally improve the lung functions in meconium aspiration syndrome. Physiol Res 12:191–200
Nkadi PO, Merritt TA, Pillers DA (2009) An overview of pulmonary surfactant in the neonate: genetics, metabolism, and the role of surfactant in health and disease. Mol Genet Metab 97:95–101
Østerholt HC, Dannevig I, Wyckoff MH, Liao J, Akgul Y, Ramgopal M, Mija DS, Cheong N, Longoria C, Mahendroo M, Nakstad B, Saugstad OD, Savani RC (2012) Antioxidant protects against increases in low molecular weight hyaluronan and inflammation in asphyxiated newborn pigs resuscitated with 100 % oxygen. PLoS ONE 7:e38839
Paterson RL, Galley HF, Webster NR (2003) The effect of N-acetylcysteine on nuclear factor-kappa B activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis. Crit Care Med 31:2574–2578
Roper JM, Mazzatti DJ, Watkins RH, Maniscalco WM, Keng PC, O’Reilly MA (2004) In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells. Am J Physiol Lung Cell Mol Physiol 286:1045–1054
Rushworth GF, Megson IL (2014) Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 141:150–159
Salvesen B, Stenvik J, Rossetti C, Saugstad OD, Espevik T, Mollnes TE (2010) Meconium-induced release of cytokines is mediated by the TRL4/MD-2 complex in a CD14-dependent manner. Mol Immunol 47:1226–1234
Soltan-Sharifi MS, Mojtahedzadeh M, Najafi A, Reza Khajavi M, Reza Rouini M, Moradi M, Mohammadirad A, Abdollahi M (2007) Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms. Hum Exp Toxicol 26:697–703
Soukka HR, Ahotupa M, Ruutu M, Kääpä PO (2002) Meconium stimulates neutrophil oxidative burst. Am J Perinatol 19:279–284
Wiswell TE, Knight GR, Finer NN et al (2002) A multicenter, randomized, controlled trial comparing surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome. Pediatrics 109:1081–1087
Zafarullah M, Li WQ, Sylvester J, Ahmad M (2003) Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 60:6–20
Acknowledgements
Authors thank Chiesi Farmaceutici for a kind donation of Curosurf and D. Kuliskova, Z. Remisova, M. Petraskova, and M. Hutko for technical assistance. This study was supported by projects APVV-0435-11, APVV-15-0075, VEGA 1/0291/12, VEGA 1/0305/14, and also by the project ‘Biomedical Center Martin’ – ITMS code: 26220220187, co-financed from EU sources.
Conflicts of Interest
The authors declare no conflict of interest in association with this study.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Mikolka, P., Kopincova, J., Mikusiakova, L.T., Kosutova, P., Calkovska, A., Mokra, D. (2016). Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury. In: Pokorski, M. (eds) Pulmonary Dysfunction and Disease. Advances in Experimental Medicine and Biology(), vol 934. Springer, Cham. https://doi.org/10.1007/5584_2016_15
Download citation
DOI: https://doi.org/10.1007/5584_2016_15
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-42009-7
Online ISBN: 978-3-319-42010-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)