You are here

Home » Content

Poliansature Yağ Asitlerinin Rat Kronik Biliyer Obstrüksiyon Modelinde Karaciğer Hasarını Azaltıcı Etkinliği

Effect of Polyunsaturated Fatty Acids on Hepatic Injury in Rats With Obstructive Jaundice

Journal Name:

  • İnönü Üniversitesi Tıp Fakültesi Dergisi

Publication Year:

  • 2008

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Aim: Cholestatic liver diseases are characterized by failure of normal amounts of physiological bile to reach the gastrointestinal tract. The failure of bile salt excretion in cholestasis leads to retention of hydrophobic bile salts within the hepatocytes and causes intrahepatic oxidative stres, persistent inflammatory responce and necrosis. The aim of this study was to assess the anti-inflammatory effects of polyunsaturated phosphatidylcholine (PPC) on liver fibrosis induced by biliary obstruction in rats. Methods: Liver fibrosis was induced in Swiss albino rats by bile duct ligation. Swiss albino rats were divided into 3 groups as follows: control group (group 1, 5 rats); rats with biliary obstruction (group 2, 10 rats); and polyunsaturated phophatidylcholine (PPC)-treated rats with biliary obstruction (Group 3, 10 rats). Biliary obstruction was induced by double ligation and division of the common bile duct. PPC treatment was started 2 weeks later from biliary obstruction in doses of 50 mg/d per rat and continued for 2 weeks. All animals were killed after 4 weeks of common bile duct ligation. Proinflammatory cytokine levels in hepatic tissues were determined by polymerase chain reaction. Results: BDL increased their secretion of both hematopoietic (granulocyte/monocyte, colony stimulating factors) and proinflammatory (interleukins 1, 6, tumor necrosis factor alpha and transforming growth factor beta) cytokines based on PCR. Administration of PPC in the rats with biliary obstruction resulted in partial inhibition of increased levels of hematopoietic and proinflammatory cytokines. Conclusion: These findings suggested that PPC can attenuate hepatic damage in extrahepatic cholestasis by preventing inflammatory process. This effect may be due to the inhibition of production of pro-inflammatory cytokines and inflammatory cells accumulation in the liver by PPC itself.
Bookmark/Search this post with
Abstract (Original Language): 
Amaç: Biliyer obstrüksiyon (BO) sonrası, safra akımın kesilmesi sonucu, hepatositlerde safra asitleri ile beraber toksik ürünlerde birikmektedir. Bunun sonucunda lipid peroksidasyonu, hepatik makrofaj aktivasyonu ve proinflamatuar stokin salınımı ortaya çıkmakta, bu da karaciğer hasarına sebep olmaktadır. Poliansature fosfatidilkolin (PFK) soyafasulyesinden elde edilen bir poliansature yağ asidi (PAYA) bileşiğidir. Memelilerdeki fosfolipidlerin bir varyansı olan PFK’nın güçlü bir sitoprotektif ve immünmodülatör etkiye sahip olduğu gösterilmiştir. Bu etkilerini göz önüne alarak rat kronik biliyer obstrüksiyon modelinde gerçekleştirdiğimiz bir deneysel çalışmada BO’da gelişen karaciğer hasarının engellenmesinde PFK’nın oldukça etkin olduğunu göstermiştik. Bu çalışmada hem biliyer obstrüksiyonlarda proinflamatuar stokinlerin rolünün hem de PFK’nın karaciğer hasarını azaltıcı etkinliklerinin altında yatan mekanizmaların ortaya konması amaçlanmıştır. Gereç ve Yöntem: Çalışmada kullanılan toplam 25 adet rat 3 gruba ayrıldı. 1. gruptaki beş rat kontrol grubunu oluştururken 2. gruptaki 10 rata biliyer obstrüksiyon uygulandı. 3. gruptaki 10 rata biliyer obstrüksiyon ile beraber PFK tedavisi verildi. PFK tedavisine kronik biliyer obstrüktif hastalıkların klinik seyrine uygun olarak obstrüksiyonun 15. gününde başlandı ve 15 gün sürdürüldü. Dört haftalık deney periyodu sonunda tüm ratlardan aynı anda karaciğer doku örnekleri alındı ve ratlar sakrifiye edildi. Karaciğer doku homojenatında, PCR ile proinflamatuar stokinlerden, interlökin 1 (IL-1), interlökin 6 (IL-6), tümör nekrozis faktör alfa (TNF α), transforming growth faktör beta (TGF β) ve granülosit-makrofaj-koloni stimülan faktör (GM-CSF) varlığı araştırıldı. Bulgular: Tüm sonuçlar değerlendirildiğinde BO sonrası proinflamatuar stokin düzeylerinin arttığı, PFK tedavisinin bu artışı önlediği tesbit edilmiştir. Sonuç: BO sonrası ortaya çıkan kalıcı inflamatuar yanıt biliyer atrezi, koledok kisti gibi hastalıklarda mortalite ve morbiditenin yüksek kalmasını sağlamaktadır. PFK’nin BO’da karaciğer hasarının engellenmesinde etkin olarak kullanılabileceği tesbit edilmiştir. PFK’nin karaciğerdeki hasarı engelleme mekanizmaları içinde proinflamatuar stokinlerin salınımını önlemesi ile gerçekleştirdiği güçlü immünmodülatör özelliğinin önemli rol oynadığını düşünmekteyiz.
FULL TEXT (PDF): 
PDF icon arastirmax-poliansature-yag-asitlerinin-rat-kronik-biliyer-obstruksiyon-modelinde-karaciger-hasarini-azaltici-etkinligi.pdf
  • 2
79-85
  • Turkish

REFERENCES

References: 

1. Benjamin IS. Biliary tract obstruction. Surgical Gastroenterology 1983;2: 105-20
2. Schaffner F, Poper H. Classification and mechanism of cholestasis. In: Wright R,
Albert KGMM, Karran S, Millvard-Sadler GDT. Liver and biliary disease:
Pathophysıology, Diagnosis, management; 2nd ed. UK: Saunders 1985: 359-86
3. Robbins S, Kumar V. Basıc Pathology; 4. baskı. Çev. EDİT. Uluoğlu Ö ve ark.
Ankara: Güneş Kitabevi 1990: 770-2
4. Kobayashi H, Puri P, Sean D, Surana R, Miyano T. Hepatic overexpression of
MHC class II antigens and macrophage-associated antigens (CD 68) in patients
with biliary atresia of poor prognosis. J Ped Surg 1997;32: 590-3
5. Blumgart LH. Surgery of the Liver and Biliary Tract; 2nd ed. UK: Longman
Group Limited 1994: 137-42
6. Slott P, Liu M, Tavaloni N. Origin, pattern, and mechanism of bile duct
proliferation following biliary obstruction in the rat. Gastroenterology 1990;99:
466-77
7. Solkol RJ, Winkloher BM, Deverazx MV, McKim JM. Generation of
hydroperoxides in isolated rat hepatocytes and hepatic mitochondria exposed to
hydrophobic bile acids. Gastroenterology 1995;109: 1249-50
8. Sigh S, Schakleton G, Ah-Sing E, Chakraborty J, Boley ME. Antioxidant defenses
in the bile duct-ligated rat. Gastroenterology 1992;103: 1625-9
9. Winwood P, Arther M. Kuppfer cells: Their activation and role in animal models
of liver injury and human liver diseases. Semin Liver Dis 1993;3: 50-9
10. Hines J, Johnson S, Burt A. In vivo responses of macrophages and perisinusoidal
cells to cholestatic liver injury. Am J Pathol 1993;142: 511-7
11. Tracy TF, Dillon P, Fox ES, et al. Inflammatory response in pediatric biliary
disease macrophage phenotype and distrubition. J Ped Surg 1996;31: 131-5
12. Kobayashi H, Yamataka A, Lane JG, Miyano T. Levels of circulating
antiinflammatory cytokine interleukin-1 receptor antagonist and proinflammatory
cytokines at different stages of biliary atresia. J Ped Surg 2002;37: 1038-41
13. Roggin KK, Kim JC, Kurkchvbasche AG, et al. Macrophage phenotype during
cholestatic injury and repair: the persistent inflammatory response. J Ped Surg
2001;36: 220-8
14. Baron V, Muriel P. Role of glutathione, lipid peroxidation and antioxidants on
acute bile-duct obstruction in the rat. Biochimica et Biophysica Acta 1999;1472:
173-80
15. Cantürk NZ, Cantürk Z, Utkan NZ, et al. Cytoprotective effect of alpha
tocopherol against liver injury induced by extrahepatic biliary obstruction. East
African Medical Journal 1998;75: 77-80
16. Karaman, A., S. Demirbilek, N. Sezgin, N. Gürbüz, İ Gürses, “Protective Effect
of Polyunsaturated Phosphatidylcholine on Liver Damage Induced by Biliary
Obstruction in Rats,” J. Pediatr. Surg 2003; 38: 1341-7
17. Lefhowith JB, Morrison A, et al. Manuplation of the acute inflammatory response
by dietary polyunsaturated fatty acid modulation. J Immunol 1990;145: 1523-9
18. Costabile M, Hii CST, Robinson BS, et al. A novel long chain polyunsaturated
fatty acid β-Oxa 21:3n-3, inhibits T lymphocyte proliferation, cytokine products,
delayed-type hypersensitivity, and carageenan-induced paw reaction and
selectively targets intracellulary signals. J Immunol 2001;167: 3980-7
19. Nielse GLKL, Faarvang BS, Thomsen KL, Teglbjaerg LT, Jensen TM, Hansen
HH, Lervang EB,Schmidt J, and Ernest E. The effect of dietary supplementation
with n-3 polyunsaturatedfatty acids in patients with rheumatoid arthritis: a
randomized double blind trial. Eur. J Clin İnvest 1992;22: 687-9
20. Ar’Rajab A, Ahren B, Rozga J, et al: Phosphatidylcholine prevents postoperative
peritoneal adhesios: an experimental study in the rat. J Surg Res 1991;50:212-5
21. Neyzi O, Ertuğrul T. Pediatri; 3. baskı. Ankara: Nobel Tıp Kitabevi. 2002: 741-5
22. Ito T, Nagaya M, et al. Modified hepatic portal enterostomy for biliary atresia. Z
Kinderchir 1984;39: 242-54
23. Dillon PW, Owings E, Cilley R, Douglas F et al. Immunosupression as adjuvant
therapy for biliary atresia. J Ped Surg 2001;36: 80-5
24. Davenport M, Kerker N, Mieli-Vergani G et al. Biliary atresia: the King’s collage
hospital experience (1974-1995) J Ped Surg 1997;32: 479-85
25. Kobayashi H, Horikoshi K, Ymataka A, et al. Are stable postoperative biliary
atresia patients really stable. Ped Surg Int 2001;17: 104-7
26. Kobayashi H, Horikoshi K, Ymataka A, et al. Beneficial effect of a traditional
herbal medicine (inchin-ko-to) in postoperative biliary atresia patients. Ped Surg
Int 2001;17: 386-9
27. Liu C, Chiu JH, Chin T, et al. Expression of aminopeptidase N in bile canaliculi:
Apredictor of clinical outcome in biliary atresia and a potential tool to implicate
the mechanism of biliary atresia. J Surg Res 2001;100: 76-83
28. Dhawan A, Trivedi P, Cheeseman p, et al. Serum hyaluronic acid as an
earlyprognostic marker in biliary atresia. J Ped Surg 2001;36: 443-6
29. Grimble RF, Tappia PS. Modulation of pro-inflammatory cytokine biology by
unsaturated fatty acids. Z Ernahrungswiss 1998;371: 57-65

Thank you for copying data from http://www.arastirmax.com