Abstract
Meconium aspiration in newborns causes lung inflammation and injury, which may lead to meconium aspiration syndrome (MAS). In this study, the effect of the antioxidant N-acetylcysteine on respiratory and inflammatory parameters were studied in a model of MAS. Oxygen-ventilated rabbits were intratracheally given 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were administered N-acetylcysteine (10 mg/kg; i.v.), or were left without treatment. The animals were oxygen-ventilated for additional 5 h. Ventilatory pressures, oxygenation, right-to-left pulmonary shunts, and leukocyte count were measured. At the end of experiment, trachea and lung were excised. The left lung was saline-lavaged and a total and differential count of cells in bronchoalveolar lavage fluid (BAL) was determined. Right lung tissue strips were used for detection of lung edema (expressed as wet/dry weight ratio) and peroxidation (expressed by thiobarbituric acid-reactive substances, TBARS). In lung and tracheal strips, airway reactivity to acetylcholine was measured. In addition, TBARS and total antioxidant status were determined in the plasma. Meconium instillation induced polymorphonuclear-derived inflammation and oxidative stress. N-acetylcysteine improved oxygenation, reduced lung edema, decreased polymorphonuclears in BAL fluid, and diminished peroxidation and meconium-induced airway hyperreactivity compared with untreated animals. In conclusion, N-acetylcysteine effectively improved lung functions in an animal model of MAS.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Choi JS, Lee HS, Seo KH, Na JO, Kim YH, Uh ST, Park CS, Oh MH, Lee SH, Kim YT (2012) The effect of post-treatment N-acetylcysteine in LPS-induced acute lung injury of rats. Tuberc Respir Dis (Seoul) 73:22–31
Domenighetti G, Quattropani C, Schaller MD (1999) Therapeutic use of N-acetylcysteine in acute lung diseases. Rev Mal Respir 16:29–37
Fu Z, Yang Z, Li A (2000) The effects of NAC on the expression and activity of SPA in rats inflicted by smoke inhalation injury. Zhonghua Shao Shang Za Zhi 16:173–176
Gillissen A, Nowak D (1998) Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir Med 92:609–623
Ivanov VA (2006) Meconium aspiration syndrome treatment – new approaches using old drugs. Med Hypotheses 66:808–810
Jansson AH, Eriksson C, Wang X (2005) Effects of budesonide and N-acetylcysteine on acute lung hyperinflation, inflammation and injury in rats. Vasc Pharmacol 43:101–111
Kharazmi A, Nielsen H, Schiøtz PO (1988) N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism. Int J Immunopharmacol 10:39–46
Koksel O, Cinel I, Tamer L, Cinel L, Ozdulger A, Kanik A, Ercan B, Oral U (2004) N-acetylcysteine inhibits peroxynitrite-mediated damage in oleic acid-induced lung injury. Pulm Pharmacol Ther 17:263–270
Lakshminrusimha S, Russell JA, Wedgwood S, Gugino SF, Kazzaz JA, Davis JM, Steinhorn RH (2006) Superoxide dismutase improves oxygenation and reduces oxidation in neonatal pulmonary hypertension. Am J Respir Crit Care Med 174:1370–1377
Lu MP, Du LZ, Gu WZ, Yu ZZ, Chen XX, Yu ZS (2005) Anti-inflammation and anti-oxidation effects of recombinant human superoxide dismutase on acute lung injury induced by meconium aspiration in infant rats. Zhejiang Da Xue Xue Bao Yi Xue Ban 34:55–59
Mahmoud KM, Ammar AS (2011) Effect of N-acetylcysteine on cardiac injury and oxidative stress after abdominal aortic aneurysm repair: a randomized controlled trial. Acta Anaesthesiol Scand 55:1015–1021
Mokra D, Mokry J, Drgova A, Petraskova M, Bulikova J, Calkovska A (2007) Intratracheally administered corticosteroids improve lung function in meconium-instilled rabbits. J Physiol Pharmacol 58(Suppl 5):389–398
Mokra D, Mokry J, Tonhajzerova I (2013) Anti-inflammatory treatment of meconium aspiration syndrome: benefits and risks. Respir Physiol Neurobiol 187:52–57
Nagata K, Iwasaki Y, Yamada T, Yuba T, Kono K, Hosogi S, Ohsugi S, Kuwahara H, Marunaka Y (2007) Overexpression of manganese superoxide dismutase by N-acetylcysteine in hyperoxic lung injury. Respir Med 101:800–807
Türüt H, Ciralik H, Kilinc M, Ozbag D, Imrek SS (2009) Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin on inflammatory and oxidant-antioxidant status after lung contusion in rats. Injury 40:521–527
Wagner PD, Mathieu-Costello O, Bebout DE, Gray AT, Natterson PD, Glennow C (1989) Protection against pulmonary O2 toxicity by N-acetylcysteine. Eur Respir J 2:116–126
Yeh ST, Guo HR, Su YS, Lin HJ, Hou CC, Chen HM, Chang MC, Wang YJ (2006) Protective effects of N-acetylcysteine treatment post acute paraquat intoxication in rats and in human lung epithelial cells. Toxicology 223:181–190
Yesilbursa D, Serdar A, Senturk T, Serdar Z, Sağ S, Cordan J (2006) Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction. Heart Vessel 21:33–37
Acknowledgements
Authors thank M. Petraskova, M. Hutko, D. Kuliskova, and Z. Remisova for technical assistance. The study was supported by the project Center of Excellence in Perinatology Research (CEPV II) No. 26220120036, it was co-financed from EU sources, by the project APVV-435-11, and grant VEGA No. 1/0057/11.
Conflicts of Interest
The authors declare no conflict of interest in relation to this article.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Mokra, D., Drgova, A., Petras, M., Mokry, J., Antosova, M., Calkovska, A. (2014). N-acetylcysteine Alleviates the Meconium-Induced Acute Lung Injury. In: Pokorski, M. (eds) Oxidative Stress and Cardiorespiratory Function. Advances in Experimental Medicine and Biology(), vol 832. Springer, Cham. https://doi.org/10.1007/5584_2014_7
Download citation
DOI: https://doi.org/10.1007/5584_2014_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-09721-3
Online ISBN: 978-3-319-09722-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)