Korean J Physiol Pharmacol.  2013 Jun;17(3):209-216. 10.4196/kjpp.2013.17.3.209.

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

Affiliations
  • 1Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea. jhjeong3@cau.ac.kr
  • 2Department of Pathology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea.
  • 3Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Korea.

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.

Keyword

Kidney; Liver; Lung; LPS; Phosphatidylcholine

MeSH Terms

Acute Kidney Injury
Animals
Cytokines
Hydrocortisone
Inflammation
Interleukin-10
Interleukin-6
Kidney
Liver
Liver Diseases
Lung
Macrophages
Neutrophils
Peroxidase
Phosphatidylcholines
Rats
Soybeans
Tumor Necrosis Factor-alpha
Cytokines
Hydrocortisone
Interleukin-10
Interleukin-6
Peroxidase
Phosphatidylcholines
Tumor Necrosis Factor-alpha

Figure

  • Fig. 1 Effects of phosphatidylchoine (PC) on serum level of TNF-α (A), IL6 (B) and IL10 (C) in lipopolysaccharide (LPS)-exposed rats. The levels of cytokines were significantly increased at 6 h after LPS injection. Pretreatment with PC (600 mg/kg, i.p.) showed protective effects on this LPS-induced increase in TNF-α and IL-6 levels. Treatment with hydrocortisone (HC, 6 mg/kg, i.v.) also attenuated the magnitude of the increase in both cytokines. Each value is the mean±SEM of 8 mice. **p<0.01 vs. LPS+Saline, ##p<0.01 vs. LPS+PC (one-way ANOVA followed by Turkey's post-test).

  • Fig. 2 Effects of PC on LPS-induced morphological changes and PMN infiltrations in lung. Representative micrographs are illustrated. An increase in PMN infiltration and thickening of alveolar septa were observed in lung tissue after LPS administration. These morphological changes were ameliorated by either HC or PC. (A) Saline+Saline (B) Saline+HC, (C) Saline+PC, (D) LPS+Saline, (E) LPS+HC and (F) LPS+PC (Hematoxylin and eosin staining; magnification, 400×).

  • Fig. 3 Effects of PC on LPS-induced morphological changes and PMN infiltrations in liver. Representative micrographs are illustrated. An increase in PMN infiltration was observed in liver tissue after LPS administration. Treatment with either HC or PC ameliorated the increase in PMN infiltrations. (A) Saline+Saline (B) Saline+HC, (C) Saline+PC, (D) LPS+Saline, (E) LPS+HC and (F) LPS+PC (Hematoxylin and eosin staining; magnification, 400×).

  • Fig. 4 Effects of PC on LPS-induced morphological changes and PMN infiltrations in kidney. Representative micrographs are illustrated. There are no significant effects of PC or HC on kidney tissue as compared to effects on lung and liver (A) Saline+Saline (B) Saline+HC, (C) Saline+PC, (D) LPS+Saline, (E) LPS+HC and (F) LPS+PC (Hematoxylin and eosin staining; magnification, 400×).

  • Fig. 5 Effects of PC on LPS-induced ED2-positive cell expression in lung. Immunohistochemistry was performed after LPS exposure. Treatment with the PC led to the attenuation of the level of ED2 positive macrophages. Representative micrographs are illustrated. (A) Saline+Saline (B) Saline+HC, (C) Saline+PC, (D) LPS+Saline, (E) LPS+HC and (F) LPS+PC (Magnification, 400×).

  • Fig. 6 Effects of PC on LPS-induced ED2-positive cell expression in liver. Immunohistochemistry was performed after LPS exposure. Treatment with the PC led to the attenuation of the level of ED2 positive macrophages. Representative micrographs are illustrated. (A) Saline+Saline (B) Saline+HC, (C) Saline+PC, (D) LPS+Saline, (E) LPS+HC and (F) LPS+PC (Magnification, 400×).

  • Fig. 7 Effects of PC on LPS-induced ED2-positive cell expression in kidney. Treatment with the PC led to the attenuation of the level of ED2 positive macrophages. Representative micrographs are illustrated. (A) Saline+Saline (B) Saline+HC, (C) Saline+PC, (D) LPS+Saline, (E) LPS+HC and (F) LPS+PC (Magnification, 400×).


Cited by  1 articles

Scant Extracellular NAD Cleaving Activity of Human Neutrophils is Down-Regulated by fMLP via FPRL1
Md. Ashraful Hasan, Md. Tipu Sultan, Won-Gyun Ahn, Yeon-Ja Kim, Ji-Hye Jang, Chang-Won Hong, Dong-Keun Song
Korean J Physiol Pharmacol. 2014;18(6):497-502.    doi: 10.4196/kjpp.2014.18.6.497.


Reference

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. PMID: 19057438.
Article
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. PMID: 18816311.
Article
3. Butt I, Shrestha BM. Two-hit hypothesis and multiple organ dysfunction syndrome. JNMA J Nepal Med Assoc. 2008; 47:82–85. PMID: 18709037.
Article
4. Krau SD. Making sense of multiple organ dysfunction syndrome. Crit Care Nurs Clin North Am. 2007; 19:87–97. PMID: 17338954.
Article
5. Mizock BA. The multiple organ dysfunction syndrome. Dis Mon. 2009; 55:476–526. PMID: 19595297.
Article
6. Lipsky M. Multiple organ dysfunction syndrome. Foreword. Dis Mon. 2009; 55:475. PMID: 19595296.
7. Johnson D, Mayers I. Multiple organ dysfunction syndrome: a narrative review. Can J Anaesth. 2001; 48:502–509. PMID: 11394523.
Article
8. Wadhwa J, Sood R. Multiple organ dysfunction syndrome. Natl Med J India. 1997; 10:277–282. PMID: 9481099.
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. PMID: 8801436.
Article
10. Henderson B, Wilson M. Modulins: a new class of cytokine-inducing, pro-inflammatory bacterial virulence factor. Inflamm Res. 1995; 44:187–197. PMID: 7655992.
Article
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. PMID: 10670840.
Article
12. Bone RC. Sepsis, the sepsis syndrome, multi-organ failure: a plea for comparable definitions. Ann Intern Med. 1991; 114:332–333. PMID: 1987879.
Article
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. PMID: 8863685.
14. Mourelle M, Guarner F, Malagelada JR. Polyunsaturated phosphatidylcholine prevents stricture formation in a rat model of colitis. Gastroenterology. 1996; 110:1093–1097. PMID: 8612998.
Article
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. PMID: 10407117.
Article
16. Blusztajn JK, Zeisel SH, Wurtman RJ. Synthesis of lecithin (phosphatidylcholine) from phosphatidylethanolamine in bovine brain. Brain Res. 1979; 179:319–327. PMID: 509240.
Article
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. PMID: 23134891.
Article
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. PMID: 7782901.
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®)-case report. Z Gastroenterol. 2011; 49:340–343. PMID: 21391165.
20. Ghyczy M, Torday C, Kaszaki J, Szabó A, Czóbel M, Boros M. Oral phosphatidylcholine pretreatment decreases ischemia-reperfusion-induced methane generation and the inflammatory response in the small intestine. Shock. 2008; 30:596–602. PMID: 18461026.
Article
21. Al-Orf SM. Effect of oxidized phosphatidylcholine on biomarkers of oxidative stress in rats. Indian J Clin Biochem. 2011; 26:154–160. PMID: 22468042.
Article
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 lipopolysaccharide-induced experimental neuroinflammation in the rat. Shock. 2011; 36:458–465. PMID: 21937953.
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. PMID: 18496240.
Article
24. Orr SK, Trépanier MO, Bazinet RP. n-3 Polyunsaturated fatty acids in animal models with neuroinflammation. Prostaglandins Leukot Essent Fatty Acids. 2013; 88:97–103. PMID: 22770766.
Article
25. Das UN. Infection, inflammation, and polyunsaturated fatty acids. Nutrition. 2011; 27:1080–1084. PMID: 21907900.
Article
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. PMID: 20832797.
Article
27. Polfliet MM, Fabriek BO, Daniëls 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. PMID: 16920481.
Article
28. Englert JA, Fink MP. The multiple organ dysfunction syndrome and late-phase mortality in sepsis. Curr Infect Dis Rep. 2005; 7:335–341. PMID: 16107229.
Article
29. Alves C, Robazzi TC, Mendonça M. Withdrawal from glucocorticosteroid therapy: clinical practice recommendations. J Pediatr (Rio J). 2008; 84:192–202. PMID: 18535733.
Article
30. Annane D. Corticosteroids for septic shock. Crit Care Med. 2001; 29(7 Suppl):S117–S120. PMID: 11445745.
Article
31. Lefering R, Neugebauer EA. Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med. 1995; 23:1294–1303. PMID: 7600840.
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. PMID: 7634816.
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. PMID: 8855809.
Article
34. Briegel J, Kellermann W, Forst H, Haller M, Bittl M, Hoffmann GE, Büchler M, Uhl W, Peter K. The Phospholipase A2 Study Group. Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome. Clin Investig. 1994; 72:782–787.
Article
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. PMID: 10436370.
Article
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. PMID: 19766625.
Article
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. PMID: 18987473.
Article
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. PMID: 9138091.
39. Riches DW, Chan ED, Winston BW. TNF-alpha-induced regulation and signalling in macrophages. Immunobiology. 1996; 195:477–490. PMID: 8933152.
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.
Article
41. Song R, Kim J, Yu D, Park C, Park J. Kinetics of IL-6 and TNF-α changes in a canine model of sepsis induced by endotoxin. Vet Immunol Immunopathol. 2012; 146:143–149. PMID: 22424937.
Article
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. PMID: 15652449.
Article
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–R277. PMID: 9688988.
Article
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. PMID: 20420568.
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. PMID: 8811559.
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. PMID: 1873355.
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. PMID: 17273473.
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. PMID: 12773517.
Article
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. PMID: 19941312.
Article
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. PMID: 22956998.
Article
Full Text Links
  • KJPP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr