DOI QR코드

DOI QR Code

Protective Effect of Phosphatidylcholine on Lipopolysaccharide-Induced Acute Inflammation in Multiple Organ Injury

  • Jung, Yoon Yang (Department of Pathology, College of Medicine, Chung-Ang University) ;
  • Nam, Yunsung (Department of Pharmacology, College of Medicine, Chung-Ang University) ;
  • Park, Yong Seol (Department of Pathology, College of Medicine, Chung-Ang University) ;
  • Lee, Ho Sung (Department of Pharmacology, College of Medicine, Chung-Ang University) ;
  • Hong, Soon Auck (Department of Pathology, College of Medicine, Chung-Ang University) ;
  • Kim, Beom Keun (Department of Pharmacology, College of Medicine, Chung-Ang University) ;
  • Park, Eon Sub (Department of Pathology, College of Medicine, Chung-Ang University) ;
  • Chung, Yoon Hee (Department of Anatomy, College of Medicine, Chung-Ang University) ;
  • Jeong, Ji Hoon (Department of Pharmacology, College of Medicine, Chung-Ang University)
  • Received : 2013.04.04
  • Accepted : 2013.04.22
  • Published : 2013.06.30

Abstract

Soybean polyunsaturated phosphatidylcholine (PC) is thought to exert anti-inflammatory activities and has potent effects in attenuating acute renal failure and liver dysfunction. The aim of this study was to investigate the effects of PC in protecting multiple organ injury (MOI) from lipopolysaccharide (LPS). Six groups of rats (N=8) were used in this study. Three groups acted as controls and received only saline, hydrocortisone (HC, 6 mg/kg, i.v.) or PC (600 mg/kg, i.p.) without LPS (15 mg/kg, i.p.) injections. Other 3 groups, as the test groups, were administered saline, HC or PC in the presence of LPS. Six hours after the LPS injection, blood and organs (lung, liver and kidney) were collected from each group to measure inflammatory cytokines and perform histopathology and myeloperoxidase (MPO) assessment. Serum cytokines (TNF-${\alpha}$, IL-6 and IL-10) and MPO activities were significantly increased, and significant histopathological changes in the organs were observed by LPS challenge. These findings were significantly attenuated by PC or HC. The treatment with PC or HC resulted in a significant attenuation on the increase in serum levels of TNF-${\alpha}$ and IL-6, pro-inflammatory cytokines, while neither PC nor HC significantly attenuated serum levels of IL-10, anti-inflammatory cytokine. In the organs, the enhanced infiltration of neutrophils and expression of ED2 positive macrophage were attenuated by PC or HC. Inductions of MPO activity were also significantly attenuated by PC or HC. From the findings, we suggest that PC may be a functional material for its use as an anti-inflammatory agent.

Keywords

References

  1. Proulx F, Joyal JS, Mariscalco MM, Leteurtre S, Leclerc F, Lacroix J. The pediatric multiple organ dysfunction syndrome. Pediatr Crit Care Med. 2009;10:12-22. https://doi.org/10.1097/PCC.0b013e31819370a9
  2. Papathanassoglou ED, Bozas E, Giannakopoulou MD. Multiple organ dysfunction syndrome pathogenesis and care: a complex systems' theory perspective. Nurs Crit Care. 2008;13:249-259. https://doi.org/10.1111/j.1478-5153.2008.00289.x
  3. Butt I, Shrestha BM. Two-hit hypothesis and multiple organ dysfunction syndrome. JNMA J Nepal Med Assoc. 2008;47: 82-85.
  4. Krau SD. Making sense of multiple organ dysfunction syndrome. Crit Care Nurs Clin North Am. 2007;19:87-97. https://doi.org/10.1016/j.ccell.2006.11.002
  5. Mizock BA. The multiple organ dysfunction syndrome. Dis Mon. 2009;55:476-526. https://doi.org/10.1016/j.disamonth.2009.04.002
  6. Lipsky M. Multiple organ dysfunction syndrome. Foreword. Dis Mon. 2009;55:475. https://doi.org/10.1016/j.disamonth.2009.04.001
  7. Johnson D, Mayers I. Multiple organ dysfunction syndrome: a narrative review. Can J Anaesth. 2001;48:502-509. https://doi.org/10.1007/BF03028318
  8. Wadhwa J, Sood R. Multiple organ dysfunction syndrome. Natl Med J India. 1997;10:277-282.
  9. Henderson B, Poole S, Wilson M. Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis. Microbiol Rev. 1996;60:316-341.
  10. Henderson B, Wilson M. Modulins: a new class of cytokineinducing, pro-inflammatory bacterial virulence factor. Inflamm Res. 1995;44:187-197. https://doi.org/10.1007/BF01782257
  11. Remick DG, Newcomb DE, Bolgos GL, Call DR. Comparison of the mortality and inflammatory response of two models of sepsis: lipopolysaccharide vs. cecal ligation and puncture. Shock. 2000;13:110-116. https://doi.org/10.1097/00024382-200013020-00004
  12. Bone RC. Sepsis, the sepsis syndrome, multi-organ failure: a plea for comparable definitions. Ann Intern Med. 1991;114: 332-333. https://doi.org/10.7326/0003-4819-114-4-332
  13. Bohlinger I, Leist M, Gantner F, Angermüller S, Tiegs G, Wendel A. DNA fragmentation in mouse organs during endotoxic shock. Am J Pathol. 1996;149:1381-1393.
  14. Mourelle M, Guarner F, Malagelada JR. Polyunsaturated phosphatidylcholine prevents stricture formation in a rat model of colitis. Gastroenterology. 1996;110:1093-1097. https://doi.org/10.1053/gast.1996.v110.pm8612998
  15. Fallbrook A, Turenne SD, Mamalias N, Kish SJ, Ross BM. Phosphatidylcholine and phosphatidylethanolamine metabolites may regulate brain phospholipid catabolism via inhibition of lysophospholipase activity. Brain Res. 1999;834:207-210. https://doi.org/10.1016/S0006-8993(99)01570-X
  16. Blusztajn JK, Zeisel SH, Wurtman RJ. Synthesis of lecithin (phosphatidylcholine) from phosphatidylethanolamine in bovine brain. Brain Res. 1979;179:319-327. https://doi.org/10.1016/0006-8993(79)90447-5
  17. Cheatham CL, Goldman BD, Fischer LM, da Costa KA, Reznick JS, Zeisel SH. Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2012;96:1465-1472. https://doi.org/10.3945/ajcn.112.037184
  18. Chung SY, Moriyama T, Uezu E, Uezu K, Hirata R, Yohena N, Masuda Y, Kokubu T, Yamamoto S. Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia. J Nutr. 1995;125:1484-1489.
  19. Rey JW, Schreiner O, Barreiros AP, Heise M, Krupp M, Schuchmann M, Otto G, Galle PR, Teufel A. Acute renal failure and liver dysfunction after subcutaneous injection of 3-snphosphatidylcholine ($Lipostabil^{(R)}$)-case report. Z Gastroenterol. 2011;49:340-343. https://doi.org/10.1055/s-0029-1245614
  20. Ghyczy M, Torday C, Kaszaki J, Szabó A, Czóbel M, Boros M. Oral phosphatidylcholine pretreatment decreases ischemiareperfusion- induced methane generation and the inflammatory response in the small intestine. Shock. 2008;30:596-602. https://doi.org/10.1097/SHK.0b013e31816f204a
  21. Al-Orf SM. Effect of oxidized phosphatidylcholine on biomarkers of oxidative stress in rats. Indian J Clin Biochem. 2011;26: 154-160. https://doi.org/10.1007/s12291-010-0064-4
  22. Tokés T, Eros G, Bebes A, Hartmann P, Várszegi S, Varga G, Kaszaki J, Gulya K, Ghyczy M, Boros M. Protective effects of a phosphatidylcholine-enriched diet in lipopolysaccharideinduced experimental neuroinflammation in the rat. Shock. 2011;36:458-465. https://doi.org/10.1097/SHK.0b013e31822f36b0
  23. Dial EJ, Zayat M, Lopez-Storey M, Tran D, Lichtenberger L. Oral phosphatidylcholine preserves the gastrointestinal mucosal barrier during LPS-induced inflammation. Shock. 2008;30: 729-733. https://doi.org/10.1097/SHK.0b013e318173e8d4
  24. Orr SK, Trepanier MO, Bazinet RP. n-3 Polyunsaturated fatty acids in animal models with neuroinflammation. Prostaglandins Leukot Essent Fatty Acids. 2013;88:97-103. https://doi.org/10.1016/j.plefa.2012.05.008
  25. Das UN. Infection, inflammation, and polyunsaturated fatty acids. Nutrition. 2011;27:1080-1084. https://doi.org/10.1016/j.nut.2011.08.001
  26. Tandy S, Chung RW, Kamili A, Wat E, Weir JM, Meikle PJ, Cohn JS. Hydrogenated phosphatidylcholine supplementation reduces hepatic lipid levels in mice fed a high-fat diet. Atherosclerosis. 2010;213:142-147. https://doi.org/10.1016/j.atherosclerosis.2010.07.050
  27. Polfliet MM, Fabriek BO, Daniels WP, Dijkstra CD, van den Berg TK. The rat macrophage scavenger receptor CD163: expression, regulation and role in inflammatory mediator production. Immunobiology. 2006;211:419-425. https://doi.org/10.1016/j.imbio.2006.05.015
  28. Englert JA, Fink MP. The multiple organ dysfunction syndrome and late-phase mortality in sepsis. Curr Infect Dis Rep. 2005;7:335-341. https://doi.org/10.1007/s11908-005-0006-0
  29. Alves C, Robazzi TC, Mendonça M. Withdrawal from glucocorticosteroid therapy: clinical practice recommendations. J Pediatr (Rio J). 2008;84:192-202. https://doi.org/10.2223/JPED.1773
  30. Annane D. Corticosteroids for septic shock. Crit Care Med. 2001;29(7 Suppl):S117-120. https://doi.org/10.1097/00003246-200107001-00036
  31. Lefering R, Neugebauer EA. Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med. 1995;23: 1294-1303. https://doi.org/10.1097/00003246-199507000-00021
  32. Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, Fisher CJ Jr. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med. 1995;23:1430-1439. https://doi.org/10.1097/00003246-199508000-00019
  33. van der Poll T, Barber AE, Coyle SM, Lowry SF. Hypercortisolemia increases plasma interleukin-10 concentrations during human endotoxemia--a clinical research center study. J Clin Endocrinol Metab. 1996;81:3604-3606.
  34. Briegel J, Kellermann W, Forst H, Haller M, Bittl M, Hoffmann GE, Büchler M, Uhl W, Peter K. Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. The Phospholipase A2 Study Group. Clin Investig. 1994;72:782-787.
  35. Osman MO, Jacobsen NO, Kristensen JU, Larsen CG, Jensen SL. Beneficial effects of hydrocortisone in a model of experimental acute pancreatitis. Dig Surg. 1999;16:214-221. https://doi.org/10.1159/000018730
  36. Hartmann P, Szabó A, Eros G, Gurabi D, Horváth G, Németh I, Ghyczy M, Boros M. Anti-inflammatory effects of phosphatidylcholine in neutrophil leukocyte-dependent acute arthritis in rats. Eur J Pharmacol. 2009;622:58-64. https://doi.org/10.1016/j.ejphar.2009.09.012
  37. Eros G, Varga G, Váradi R, Czóbel M, Kaszaki J, Ghyczy M, Boros M. Anti-inflammatory action of a phosphatidylcholine, phosphatidylethanolamine and N-acylphosphatidylethanolamine- enriched diet in carrageenan-induced pleurisy. Eur Surg Res. 2009;42:40-48. https://doi.org/10.1159/000167856
  38. Aono K, Isobe K, Kiuchi K, Fan ZH, Ito M, Takeuchi A, Miyachi M, Nakashima I, Nimura Y. In vitro and in vivo expression of inducible nitric oxide synthase during experimental endotoxemia: involvement of other cytokines. J Cell Biochem. 1997;65:349-358. https://doi.org/10.1002/(SICI)1097-4644(19970601)65:3<349::AID-JCB5>3.0.CO;2-S
  39. Riches DW, Chan ED, Winston BW. TNF-alpha-induced regulation and signalling in macrophages. Immunobiology. 1996;195:477-490. https://doi.org/10.1016/S0171-2985(96)80017-9
  40. Qiu P, Cui X, Barochia A, Li Y, Natanson C, Eichacker PQ. The evolving experience with therapeutic TNF inhibition in sepsis: considering the potential influence of risk of death. Expert Opin Investig Drugs. 2011;20:1555-1564. https://doi.org/10.1517/13543784.2011.623125
  41. Song R, Kim J, Yu D, Park C, Park J. Kinetics of IL-6 and TNF-$\alpha$ changes in a canine model of sepsis induced by endotoxin. Vet Immunol Immunopathol. 2012;146:143-149. https://doi.org/10.1016/j.vetimm.2012.02.008
  42. Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine. 2005;29:169-175. https://doi.org/10.1016/j.cyto.2004.10.010
  43. Leon LR, White AA, Kluger MJ. Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice. Am J Physiol. 1998;275:R269-277.
  44. Neri M, Bello S, Bonsignore A, Centini F, Fiore C, Földes-Papp Z, Turillazzi E, Fineschi V. Myocardial expression of TNFalpha, IL-1beta, IL-6, IL-8, IL-10 and MCP-1 after a single MDMA dose administered in a rat model. Curr Pharm Biotechnol. 2010;11:413-420. https://doi.org/10.2174/138920110791591517
  45. Refsum SE, Halliday MI, Campbell G, McCaigue M, Rowlands BJ, Boston VE. Modulation of TNF alpha and IL-6 in a peritonitis model using pentoxifylline. J Pediatr Surg. 1996; 31:928-930. https://doi.org/10.1016/S0022-3468(96)90413-3
  46. Engelberts I, von Asmuth EJ, van der Linden CJ, Buurman WA. The interrelation between TNF, IL-6, and PAF secretion induced by LPS in an in vivo and in vitro murine model. Lymphokine Cytokine Res. 1991;10:127-131.
  47. Butterfield TA, Best TM, Merrick MA. The dual roles of neutrophils and macrophages in inflammation: a critical balance between tissue damage and repair. J Athl Train. 2006;41:457-465.
  48. Reumaux D, de Boer M, Meijer AB, Duthilleul P, Roos D. Expression of myeloperoxidase (MPO) by neutrophils is necessary for their activation by anti-neutrophil cytoplasm autoantibodies (ANCA) against MPO. J Leukoc Biol. 2003; 73:841-849. https://doi.org/10.1189/jlb.1102567
  49. Pils MC, Pisano F, Fasnacht N, Heinrich JM, Groebe L, Schippers A, Rozell B, Jack RS, Müller W. Monocytes/ macrophages and/or neutrophils are the target of IL-10 in the LPS endotoxemia model. Eur J Immunol. 2010;40:443-448. https://doi.org/10.1002/eji.200939592
  50. Zhou X, Liu Z, Jang F, Xiang C, Li Y, He Y. Autocrine Sonic hedgehog attenuates inflammation in cerulein-induced acute pancreatitis in mice via upregulation of IL-10. PLoS One. 2012;7:e44121. https://doi.org/10.1371/journal.pone.0044121

Cited by

  1. Repeated Intratracheal Instillation of PM10 Induces Lipid Reshaping in Lung Parenchyma and in Extra-Pulmonary Tissues vol.9, pp.9, 2013, https://doi.org/10.1371/journal.pone.0106855
  2. The promise of curcumin-phosphatidylcholine complex for cardiometabolic diseases: more than just ‘more curcumin’ vol.29, pp.5, 2013, https://doi.org/10.1080/14786419.2014.947494
  3. Hyperreactivity of Blood Leukocytes in Patients with NAFLD to Ex Vivo Lipopolysaccharide Treatment Is Modulated by Metformin and Phosphatidylcholine but Not by Alpha Ketoglutarate vol.10, pp.12, 2013, https://doi.org/10.1371/journal.pone.0143851
  4. Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation into Cancer and Nutrition–Potsdam Study vol.68, pp.2, 2016, https://doi.org/10.1161/hypertensionaha.116.07292
  5. Exogenous phosphatidylcholine supplementation retrieve aluminum-induced toxicity in male albino rats vol.24, pp.18, 2017, https://doi.org/10.1007/s11356-017-9151-x
  6. Phospholipids of Animal and Marine Origin: Structure, Function, and Anti-Inflammatory Properties vol.22, pp.11, 2013, https://doi.org/10.3390/molecules22111964
  7. Choline Regulates the Function of Bovine Immune Cells and Alters the mRNA Abundance of Enzymes and Receptors Involved in Its Metabolism in vitro vol.9, pp.None, 2018, https://doi.org/10.3389/fimmu.2018.02448
  8. Glycerophospholipid Supplementation as a Potential Intervention for Supporting Cerebral Structure in Older Adults vol.10, pp.None, 2013, https://doi.org/10.3389/fnagi.2018.00049
  9. Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung Inflammation in Rats vol.2018, pp.None, 2013, https://doi.org/10.1155/2018/7019759
  10. Physiological parameters and productive performance of rabbit does and their offsprings with dietary supplementation of soy lecithin vol.53, pp.9, 2018, https://doi.org/10.1590/s0100-204x2018000900012
  11. Phosphatidylcholine attenuated docetaxel-induced peripheral neurotoxicity in rats vol.41, pp.4, 2018, https://doi.org/10.1080/01480545.2017.1390580
  12. L-α-Phosphatidylcholine attenuates mercury-induced hepato-renal damage through suppressing oxidative stress and inflammation vol.26, pp.9, 2013, https://doi.org/10.1007/s11356-019-04395-9
  13. Gut microbiota signatures and lipids metabolism profiles by exposure to polyene phosphatidylcholine vol.45, pp.3, 2019, https://doi.org/10.1002/biof.1495
  14. High-Density Lipoproteins Decrease Proinflammatory Activity and Modulate the Innate Immune Response vol.39, pp.12, 2019, https://doi.org/10.1089/jir.2019.0029
  15. Phosphatidylcholine Ameliorates LPS-Induced Systemic Inflammation and Cognitive Impairments via Mediating the Gut-Brain Axis Balance vol.68, pp.50, 2013, https://doi.org/10.1021/acs.jafc.0c06383
  16. The Potential for Phospholipids in the Treatment of Airway Inflammation: An Unexplored Solution vol.14, pp.None, 2013, https://doi.org/10.2174/1874467214666210208114439
  17. Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks vol.28, pp.1, 2013, https://doi.org/10.1080/10717544.2021.1905747