Journals / Türk Anestezi ve Reanimasyon Dergisi / 2005 / Cilt: 33 - Sayı: 6

Effects of cyclosporin-A and NF-kB expression in illeum and lung tissue in a CLP-induced experimental sepsis model

Deneysel sepsis modelinde siklosporin-A'nın akciğer ve ileum dokusunda apoptozis ve nükleer faktör-kappaB ekspresyonuna etkileri

Pages
451–462
Publication Date
2022-11-05
DOI
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Histopathology was performed with hemotoxilen-eosine staining and NF-kB expression was assessed immunohistochemically.Results: CLP-induced sepsis significantly increased ileal tissue 3-NT levels p=

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Objective & Hypothesis:Aim: We investigated the effects of Cyclosporin-A (CsA) on reactive oxygen and nitrogen species, apoptosis and expression of NF-kB in ileum and lung tissues in a cecal ligation and puncture (CLP) induced experimental sepsis.Material and Method: After ethics committee approval, 60 male Wistar rats (200-250 gr) were randomized to four groups: Group I; control group (sham) (n=15), Group II; CLP group (n=15), Group III; sham+CsA (n=15), Group IV; CLP+CsA group (n=15).
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Key Findings & Data:Groups III and IV received intraperitoneal CsA (10 mg kg-1) 6 and 24 hours following surgery. 36 hours later specimens of ileum and lung were excised.Malondialdehid (MDA) and 3-l nitrotyrosine (3-NT) were measured biochemically and "DNA laddering" was evaluated by agarose-gel electrophoresis.
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Conclusion & Impact:Histopathology was performed with hemotoxilen-eosine staining and NF-kB expression was assessed immunohistochemically.Results: CLP-induced sepsis significantly increased ileal tissue 3-NT levels p=
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Aim: We investigated the effects of Cyclosporin-A (CsA) on reactive oxygen and nitrogen species, apoptosis and expression of NF-kB in ileum and lung tissues in a cecal ligation and puncture (CLP) induced experimental sepsis.Material and Method: After ethics committee approval, 60 male Wistar rats (200-250 gr) were randomized to four groups: Group I; control group (sham) (n=15), Group II; CLP group (n=15), Group III; sham+CsA (n=15), Group IV; CLP+CsA group (n=15). Groups III and IV received intraperitoneal CsA (10 mg kg-1) 6 and 24 hours following surgery. 36 hours later specimens of ileum and lung were excised.Malondialdehid (MDA) and 3-l nitrotyrosine (3-NT) were measured biochemically and "DNA laddering" was evaluated by agarose-gel electrophoresis. Histopathology was performed with hemotoxilen-eosine staining and NF-kB expression was assessed immunohistochemically.Results: CLP-induced sepsis significantly increased ileal tissue 3-NT levels p=

Özet

Amaç: Çalışmamızda Siklosporin A'nın (CsA); Çekal ligasyon ve delme (CLP) ile deneysel sepsis modelinde ve akciğer dokularında reaktif oksijen ve nitrojen türevleri aracılı sitotoksisitede, doku apoptozisinde ve nükleer faktor-kappa B (NF-kB) ekspresyonundaki olası etkileri değerlendirildi.Gereç ve Yöntem: Fakülte etik kurul onayı alındıktan sonra 220-250 gr. ağırlıklarında 60 erkek Wistar rat rasgele 4 eşit gruba ayrıldı; I-Kontrol grubu (n=15), II-CLP grubu (n=15), III-CsA uygulanan kontrol grubu (n=15), IV-CLP + CsA uygulanan grup (n=15). III. ve IV. gruptaki ratlara; laparotomi işleminden sonra 6. ve 24. saatlerde 10 mg kg-1 dozda Siklosporin-A (CsA) intraperitoneal olarak verildi. 36. saatte tüm ratlardan akciğer ve ileum doku örnekleri alındı. Doku örneklerinde malondialdehit (MDA) ve 3-L nitrotirozin (3-NT) düzeyleri ölçüldü, agaroz-jel elektroforez yöntemiyle "DNA laddering" çalışıldı. Doku histopatolojisi hematoksilen-eozin boyama ile nükleer faktor-kappa B ekspresyonu ise immunhistokimyasal boyama ile değerlendirildi.Bulgular: CLP grubunda ileum dokusunda ölçülen 3-NT değerleri belirgin arttı. CLP+CsA grubunda ise bu artışın önlendiği saptandı. Doku MDA düzeylerinde; gerek ileum gerekse akciğer dokularında gruplar arasında anlamlı bir farklılık izlenmedi (p=0.119). Histopatolojik değerlendirmede; CLP grubunda morfolojik hasarlanma bulgularının görülmesine ragmen, CLP+CsA grubunda ise bu değişiklikler daha azdı. ‹leum dokusunda Siklosporin-A tedavisiyle agaroz-jel elektroforez yöntemiyle ölçülen DNA kırılmalarının % 25 oranında önlendiği izlendi. NF-kB ekspresyonunda ileum ve akciğer dokusunda gruplar arasında immunohistokimyasal olarak bir farklılık izlenmedi.Sonuç: Sonuçlarımız sepsis modelinde Siklosporin-A'nın ileum ve akciğer dokusunda hasarlanmayı önlediği yönündedir. Bu bulgular Siklosporin-A'nın ‹leum dokusunda peroksinitrit kökenli hasarlanmayı önlerken apoptozisi de baskıladığını göstermektedir. Sepsis tedavisinde, Siklosporin-A'nın hücresel düzeyde etkin olduğu düşünüyoruz.

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Cite This Article

OKÇU, H., CİNEL, İ., CİNEL, L., POLAT, G., ORAL, U. (2022). Effects of cyclosporin-A and NF-kB expression in illeum and lung tissue in a CLP-induced experimental sepsis model. Türk Anestezi ve Reanimasyon Dergisi, Cilt: 33 - Sayı: 6, 451–462. https://ajindex.com/articles/620101

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References (15)

  1. Wood KA, Angus DC. Genetic epidemiollogy of sepsis and Peptic shock. Semin Respir Crit Care Med. 2004; 25:611-8
  2. Ayala A, Lomas J, Grutkoski P, Chung CS Patholo- gical aspects of apoptosis in severe sepsis and shock? Int JBiochem & Cell Bid 2003; 35:7-15
  3. Hotchkiss RS, Swanson PE, Freeman BD, et al. Apoptotic cell death in paints with sepsis,shock and multiple organ dysfunction.Crit Care Med 1999; 27:1230-1251
  4. Cinel I, Buyukafsar K, Cinel L et al. The role of poly (ADP-ribose) synthetase inhibition in preventing endotoxemia-induced intestinal epithelial apoptosis. Pharm Res 2002; 46:119-127
  5. Nadler EP, Ford HR. Regulation of bacterial translocation by nitric oxide. Pediatr Surg Int 2000; 16:165-168
  6. Ozdülger A, Cinel I, Köksel O, et al. The Protective Effect of N-Acetylcysteine on Apoptotic Lung Injury in Cecal Ligation and Puncture-Induced Sepsis Model. Shock 2003; 19:366-372
  7. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003; 348:138-150
  8. Singer M, Brealey D. Mitochondrial dysfunction in sepsis. Curr Infect Dis Rep 2003; 5:365-371. 9.Sayeed MM.Mitochondrial dysfunction in sepsis: A familiar song with new lyrics. Crit Care Med 2002; 30:2780- 2781
  9. Brealey D, Karyampudi S, Jacques TS, et al. Mitochondrial dysfunction in a long-term rodent model of sepsis and organ failure. Am J Physiol Regul Integr Comp Physiol 2004; 286:491-497
  10. Boulos M, Astiz ME, Barua RS, et al. Impaired mitochondrial function induced serum from septic shock patients is attenuated by inhibition of nitric oxide synthase and poly (ADP-ribose) synthase. Crit Care Med 2003; 31:353-358
  11. Griffiths EJ, Halestrap AP. Protection by cyclosporin -A of ischaemia/reperfusion-induced damage in isolated rat hearts. J Mol Cell Cardiol 1993; 25:1461-1469
  12. Halestrap AP, Connern CP, Griffths EJ, Kerr PM. Cyclosporin-A binding to mitochondrial cyclophilin inhibits the permeability transition pore and protects hearts from ischaerhia/reperfusion injury. Mol Cell Biochem 1997; 174:167-172
  13. Crouser ED, Julian MW, Joshi MS, et al. Cyclosporin A ameliorates mitochondrial ultrastructural injury in the ileum during acute endotoxerriia. Crit Care Med 2002; 30:2722-2728
  14. Hiroshi O, Nobuko Q, Kunio Y. Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 1979; 95:351-358
  15. Chui CJ, McArdle AH, Brown R, et al. Intestinal mucosal lesion in low-flow states. Arch Surg 1970; 101:478-4