The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Relationship between Pulmonary Surfactant Protein and Lipid Peroxidation in Lung Injury due to Paraquat Intoxication in Rats

  • Gil, Hyo-Wook (Department of Internal Medicine, Soonchunhyang University Medical College, Cheonan Hospital) ;
  • Oh, Mi-Hae (Departments of Pathology, Soonchunhyang University Medical College, Cheonan Hospital) ;
  • Woo, Kee-Min (Departments of Biochemistry, Soonchunhyang University Medical College, Cheonan Hospital) ;
  • Lee, Eun-Young (Departments of Internal Medicine, Soonchunhyang University Medical College, Cheonan Hospital) ;
  • Oh, Myung-Ho (Departments of Pediatrics, Soonchunhyang University Medical College, Cheonan Hospital) ;
  • Hong, Sae-Yong (Departments of Internal Medicine, Soonchunhyang University Medical College, Cheonan Hospital)
  • Published : 20070600
⟨ Previous Next ⟩

Abstract

Background : Pulmonary damage resulting from lipid peroxidation is a principal effect of paraquat intoxication. The host-defense functions of surfactant are known to be mediated by the surfactant proteins A and D (SP-A and SP-D, respectively). The primary objective of this study was to evaluate the variations over time in levels of surfactant protein and lipid peroxidation (LPO) in lung tissue following free-radical-induced injury. Methods : 42 adult, male, Sprague-Dawley rats were administered intraperitoneal injections of paraquat (35 mg/kg body weight). SP-A and SP-D levels were determined via Western blot. LPO in the left lung homogenate was measured via analyses of the levels of thiobarbituric acid-reactive substances. Results : LPO levels peaked at 6 hours, with no associated histological changes. SP-D levels increased until hour 12 and declined until hour 48; SP-D levels subsequently began to increase again, peaking at hour 72. SP-A levels peaked at hour 6, declining thereafter. Conclusions : We suggest that in the early phase of paraquat injury, SP-D levels reflect alveolar damage and that de novo synthesis of SP-D takes 72 hours. Levels of SP-A, on the other hand, reflect abnormalities in the surfactant system in the late stage of paraquat intoxication. Surfactant proteins may play a role in protecting the lungs from reactive oxygen injury. A time-dependent variation has been observed in the levels of surfactant proteins A and D following paraquat injury, and it has been suggested that these proteins play a role in the protection of lung tissue against ROS-induced injuries.

Keywords

Acknowledgement

This work was supported by the Division of Academic Research of Soonchunhyang University.

References

  1. Rose MS, Smith LL, Wyatt I. Evidence for energy-dependent accumulation of paraquat into rat lung. Nature 252:314-315, 1974
  2. Forman HJ, Aldrich TK, Posner MA, Fisher AB. Differential paraquat uptake and redox kinetics of rat granular pneumocytes and alveolar macrophages. J Pharmacol Exp Ther 221:428-433, 1982
  3. Winchester JF. Paraquat and the bipyridyl herbicides. In: Hadadad LM, Winchester JF, eds. Clinical management of poisoning and drug overdose. 2nd ed. p. 1088-1103, Philadelphia, WB Saunders, 1990
  4. Manktelow BW. The loss of pulmonary surfactant in paraquat poisoning: a model of the study of the respiratory distress syndrome. Br J Exp Pathol 48:366-369, 1967
  5. Clark HW, Reid KB, Sim RB. Collectins and innate immunity in the lung. Microbes Infect 2:273-278, 2000 https://doi.org/10.1016/S1286-4579(00)00301-4
  6. LeVine AM, Whitsett JA. Pulmonary collectins and innate host defense of the lung. Micobes Infect 3:161-166, 2001 https://doi.org/10.1016/S1286-4579(00)01363-0
  7. Botas C, Poulain F, Akiyama J, Brown C, Allen L, Goerke J, Clements J, Carlson E, Gillespie AM, Epstein C, Hawgood S. Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D. Proc Natl Acad Sci U S A 95:11869-11874, 1998
  8. Wert SE, Yoshida M, LeVine AM, Ikegami M, Jones T, Ross GF, Fisher JH, Korfhagen TR, Whitsett JA. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proc Natl Acad Sci U S A 97:5972-5977, 2000
  9. Barrios R, Pardo A, Ramos C, Montano M, Ramirez R, Selman M. Upregulation of acidic fibroblast growth factor during development of experimental lung fibrosis. Am J Physiol 273:L451-L458, 1997
  10. Selman M, Montano M, Ramos C, Barrios R, Perez-Tamayo R. Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study. Exp Mol Pathol 50:147-166, 1989 https://doi.org/10.1016/0014-4800(89)90027-0
  11. Peterson GL. Determination of total protein. Methods Enzymol 91:95-119, 1983 https://doi.org/10.1016/S0076-6879(83)91014-5
  12. Fisher HK, Clements JA, Wright RR. Pulmonary effects of the herbicide paraquat studied 3 days after injection in rats. J Appl Physiol 35:268-273, 1973 https://doi.org/10.1152/jappl.1973.35.2.268
  13. Fisher HK, Clements JA, Tierney DF, Wright RR. Pulmonary effects of paraquat in the first day after injection. Am J Physiol 228:1217-1223, 1975
  14. Robertson B, Enhorning G, Ivemark B, Malmqvist E, Modee J. Experimental respiratory distress induced by paraquat. J Pathol 103:239-244, 1971 https://doi.org/10.1002/path.1711030406
  15. Risberg B, Smith L, Ortenwall P. Oxygen radicals and lung injury. Acta Anaesthesiol Scand Suppl 95:106-118, 1991
  16. Smith LL. The toxicity of paraquat. Adverse Drug React Acute Poisoning Rev 7:1-17, 1988
  17. Tominack RL, Pond SM. Herbicide. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman RS, Nelson LS, eds. Goldfrank's toxicologic emergencies. 7th ed. p. 1393-1410, USA, McGraw-Hill, 2002
  18. Chen CM, Lua AC. Lung toxicity of paraquat in the rat. J Toxicol Environ Health A 60:477-487, 2000 https://doi.org/10.1080/00984100050079548
  19. Nogee LM. Alterations in SP-B and SP-C expression in neonatal lung disease. Annu Rev Physiol 66:601-623, 2004 https://doi.org/10.1146/annurev.physiol.66.032102.134711
  20. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5:58-68, 2005 https://doi.org/10.1038/nri1528
  21. Wright JR. Immunomodulatory functions of surfactant. Physiol Rev 77:931-962, 1997 https://doi.org/10.1152/physrev.1997.77.4.931
  22. Cockshutt AM, Weitz J, Possmayer F. Pulmonary surfactantassociated protein A enhances the surface activity of lipid extract surfactant and reverses inhibition by blood proteins in vitro. Biochemistry 29:8424-8429, 1990 https://doi.org/10.1021/bi00488a032
  23. Suzuki Y, Fujita Y, Kogishi K. Reconstitution of tubular myelin from synthetic lipids and proteins associated with pig pulmonary surfactant. Am Rev Respir Dis 140:75-81, 1989 https://doi.org/10.1164/ajrccm/140.1.75
  24. Fisher AB, Dodia C, Chander A. Inhibition of lung calciumindependent phospholipase A2 by surfactant protein A. Am J Physiol 267:L335-L341, 1994
  25. Touqui L, Arbibe L. A role for phospholipase A2 in ARDS pathogenesis. Mol Med Today 5:244-249, 1999 https://doi.org/10.1016/S1357-4310(99)01470-7
  26. Bridges JP, Davis HW, Damodarasamy M, Kuroki Y, Howles G, Hui DY, McCormack FX. Pulmonary surfactant proteins A and D are potent endogenous inhibitors of lipid peroxidation and oxidative cellular injury. J Biol Chem 275:38848-38855, 2000 https://doi.org/10.1074/jbc.M005322200
  27. Clark H, Palaniyar N, Strong P, Edmondson J, Hawgood S, Reid KB. Surfactant protein D reduces alveolar macrophage apoptosis in vivo. J Immunol 169:2892-2899, 2002 https://doi.org/10.4049/jimmunol.169.6.2892
  28. Pan T, Nielsen LD, Allen MJ, Shannon KM, Shannon JM, Selman M, Mason RJ. Serum SP-D is a marker of lung injury in rats. Am J Physiol Lung Cell Mol Physiol 282:L824-L832, 2002 https://doi.org/10.1152/ajpcell.00388.2001
  29. Gommers D, Eijking EP, So KL, van't Veen A, Lachmann B. Bronchoalveolar lavage with a diluted surfactant suspension prior to surfactant instillation improves the effectiveness of surfactant therapy in experimental acute respiratory distress syndrome (ARDS). Intensive Care Med 24:494-500, 1998 https://doi.org/10.1007/s001340050602
  30. Harris JD, Jackson F Jr, Moxley MA, Longmore WJ. Effect of exogenous surfactant instillation on experimental acute lung injury. J Appl Physiol 66:1846-1851, 1989 https://doi.org/10.1152/jappl.1989.66.4.1846