Influence of Long-Term Inhaled Glucocorticoids on the Lung Surfactant Phospholipid Levels in Rats

ORIGINAL ARTICLE
Oleg A. Rosenberg, MD, PhD, ScD¹*; E.S. Lebedeva, MD, PhD²; L.V. Loshakova; A.Ed. Shulga¹; A.A. Seiliev, PhD¹; V.A. Volchkov, MD, PhD, ScD¹

¹ Russian Research Center of Radiology and Surgery Technologies, St. Petersburg, Russia; ²Pulmonology Research Institute, St. Petersburg, Russia

*Corresponding author: Prof. Oleg Rosenberg, MD, PhD, ScD. Department of Medical Biotechnology of Russian Research Center of Radiology and Surgery Technologies, St. Petersburg, Russia. E-mail: rozenberg@biosurf.ru

Published: September 12, 2016.  DOI: 10.21103/Article6(3)_OA1

Abstract: 

Background: Damage to lung surfactant, which is responsible for the lung local immunity, may contribute to the development of bronchial inflammation in patients with bronchial asthma. Different doses of glucocorticoids produce a stimulating or inhibiting effect on the synthesis of the surfactant protein (SP-A) mRNA. Lung surfactant disorders may negatively influence bronchial homeostasis and aggravate the condition of patients with bronchial asthma and COPD. The objective of this study was to evaluate the influence of long-term inhaled corticosteroids on the phospholipid levels of the lung surfactant in rats.
Methods and Results: Inhalations of prednisolone hemisuccinate (PH) were given to white non-pedigree rats weighing 180-200g at a dose of 0.3mg/kg daily for 30 days. Already by the end of the first study period (10 days), lung surfactant phospholipid levels were found to decrease significantly from 1.35±0.060mg to 1.02±0.045mg (P<0.001). The decrease was further recorded at Day 20 and Day 30 of the inhalation period: down to 0.94±0.042 mg (P<0.001) and 1.04±0.047mg (P<0.01), respectively. The phospholipid content continued to decrease after termination of inhalations down to 0.80±0.036mg (P<0.001) and 0.63±0.028mg (P<0.001) at Day 40 and 50 of the experiment. By Day 60 of the experiment (30 days after termination of PH), the phospholipid content in the lung surfactant was restored to the baseline level of 1.29±0.058mg.
Conclusion: The content of lung surfactant was found to decrease significantly as a result of long-term ICS treatment, which may have a negative effect for chronic lung diseases.

Keywords: 
inhaled corticosteroids; lung surfactant; COPD; bronchial asthma.
References: 
  1. Kelly HW, Nelson HS. Potential adverse effects of the inhaled corticosteroids. J Allergy Clin Immunol. 2003; 112(3):469–78.
  2. Rosenberg O, Seiliev A, Zhuikov A. Lung surfactant: correlation between biophysical characteristics, composition, and therapeutic efficacy. In: Gregoriadis G., editor. Liposome Technology. New York: Informa Healthcare; 2006:317–345.
  3. Hohlfeld JM. The role of surfactant in asthma. Respir Res. 2002; 3(1):4.. doi:10.1186/rr176.
  4. Cheng G, Ueda T, Sugiyama K, Toda M, Fukuda T. Compositional and functional changes of pulmonary surfactant in a guinea-pig model of chronic asthma. Respir Med. 2001; 95(3):180–6.
  5. Mwansa-Kambafwile J, Cousens S, Hansen T, Lawn JE. Antenatal steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth. Int J Epidemiol. 2010; 39 (Suppl 1):i122-33.
  6. Volchkov V, Dubrovskaya V, Danilov L, Rosenberg O. Modification of X-ray alveolitis in rat lungs by intratracheal administration of phosphatidylcholine-cholesterol liposomes. Eur Respir J. 2002; 20 (Suppl 38):486s.
  7. Floros J, Phelps DS, Pison U, Spragg R. Pulmonary surfactant-update on function, molecular biology and clinical implications. Curr Respir Med Rev. 2005; 1(1):77–84.
  8. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J of Biochem Physiol. 1959; 37(8):911-7.
  9. Vaskovsky VE, Kostetsky EY. A universal reagent for phospholipid analysis. J Chromatogr. 1975; 114 (1):129-41.
  10. Hoover RR, Floros J. SP-A 3'-UTR is involved in the glucocorticoid inhibition of human SP-A gene expression. Am J Physiol. 1999; 276(6 Pt 1):L917–24.
  11. Liley HG, White RT, Benson BJ, Ballard PL. Glucocorticoids both stimulate and inhibit production of pulmonary surfactant protein A in fetal human lung. Proc Natl Acad Sci USA. 1988; 85(23):9096–100.
  12. Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013; 68(11):1029–36.
  13. Rozenberg OA. Pulmonary Surfactants for Acute and Chronic Lung Diseases (Part II). General Reanimatology. 2014; 10 (5):69-86.
  14. Rosenberg O, Alekseev A, Iakovlev A, Shvechkova M, Seiliev A, Volchkov V. Surfactant therapy of A/H1N1 severe pneumonia and ARDS is a chance for survival. Eur Respir J. 2010; 56 (Suppl 54): 772.
  15. Rosenberg OA, Kirillov YA, Danilov LN, Loshakova LV, Lebedeva ES, Shylga AE, Sеs TP. The lung surfactant immune system response to intratracheal administration of “empty” liposomes. J Liposome Research. 1994; 4(1):203-212.
  16. Soll R, Ozek E. Multiple versus single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome. Cochrane Database Syst Rev. 2009; 1: CD000141. doi: 10.1002/14651858

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