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Pars Inhibitor 3-Aminobenzamide Attenuates Lung Injury in Experimental Endotoxemia

Yıl 2005, Cilt: 12 Sayı: 2, 63 - 66, 01.04.2005

Öz

Background: The role of poly(ADP-ribose) synthetase (PARS) inhibitor 3-aminobenzamide on lung injury was investigated in endotoxin-induced sepsis in 21 male Wistar rats (250-300 g) allocated into three groups. Methods: The control group, received intraperitoneal saline (1ml kg-1 : n=7); the second group, intraperitoneal endotoxin (Escherichia coli lipopolysaccharide 055:B5 10 mg kg-1 :n=7); the third group, intraperitoneal 3-aminobenzamide 10mg kg-1 and 1 ml kg-1 saline 10 min before endotoxin (n=7). Six hours later, rats were sacrified with overdose of anaesthetic. Bronchoalveolar lavage (BAL) of the right lung was performed and used for assey of protein concentration and neutrophil count. The wet/dry lung ratio of the left lower lobe was calculated. Intravascular neutrophils of the left lung were cleared out with saline and asseyed spectrophotometrically for myeloperoxidase activity. For statistical evaluation analysis of variance was used. Results: When compared with controls, administration of endotoxin caused a significant increase in mean pulmonary myeloperoxidase activity which was associated with an increase in mean BAL neutrophil concentration and mean lung wet:dry weight ratios as an expression of pulmonary extravascular lung water and microvascular leakage of protein The increase in these values were not significant in the endotoxin+3-AB group. Conclusion: The results of this study show that endotoxin challenge is associated with marked pulmonary injury and part of the anti-inflamatory effect of PARS in this injury may be related to the reduction of neutrophil recruitment into the inflamatory site. Key words: Sepsis, 3-Aminobenzamide, Pulmonary injury

Kaynakça

  • Altuntaş Y, Köksal G M, Sayılgan C, et al. Tavşanlarda oluşturulan intraabdominal SIRS modelinde erken dönemde oluşan değişikliklerin araştırılması. Göğüs Kalp Damar Anestezi ve Yoğun Bakım Derneği Dergisi 2003; 9: 4-10.
  • Bone RC. The pathogenesis of sepsis. Ann Intern Med 1991; 115: 457 – 469.
  • Wolfe TA, Dasta JF. Use of nitric oxide synthase inhibitors as a novel treatment for septic shock. Ann Pharmacother 1995; 29: 36 – 46.
  • Mercer DW, Smith GS, Cross JM, et al. Effect of Lipopolisaccharide on intestinal injury: Potential role of nitric oxide and lipid peroxidation. J Surg Res 1996; 63: 185 - 92.
  • Oliver FJ, Menissier-de Murcia J, Nacci C, et al. Resistance to endotoxic shock as a consequence of defective NF-kappaB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J 1999; 18: 4446-4454
  • Szabo C, Zingarelli B, Salzman AL. Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite. Circ Res 1996; 78: 1051 – 1063.
  • Szabo C. DNA strand breakage and activation of poly-ADP ribosyltransferase: A cytotoxic pathway triggered by peroxynitrite. Free Rad Biol Med 1996; 21: 855 –869.
  • Farivar AS, Woolley SM, Fraga CH,et al. Intratracheal poly (ADP) ribose synthetase inhibition ameliorates lung ischemia reperfusion injury. Ann Thorac Surg 2004 ;77(6):1938- 1943.
  • Bowes J, McDonald MC, Piper J, et al. Inhibitors of poly (ADP-ribose) synthetase protect rat cardiomyocytes against oxidant stress. Cardiovasc Res 1999; 41: 126 – 134.
  • Cuzzocrea S, Zingarelli B, Costantino G, Sottile A, Teti D, Caputi AP. Protective effect of poly(ADP-ribose) synthetase inhibition on multiple organ failure after zymosan- induced peritonitis in the rat. Crit Care Med 1999; 27(8): 1517 – 1523.
  • Cuzzocrea S, Thiemermann C, Salvemini D, et al. Potential therapeutic effect of antioxidant therapy in shock and inflammation. Curr Med Chem. 2004 ;11(9):1147-1162.
  • 12-Virag L, Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 54: 375-429, 2002)
  • Szabo A, Salzman A L, Szabo C. Poly (ADP-Ribose) Synthetase activation mediates pulmonary microvascular and intestinal mucosal dysfunction in endotoxin shock. Life Sciences 1998; 63: 2133-2139.
  • Wizemann TM, Gardner CR, Laskin JD, et al. Production of nitric oxide and peroxynitrite in the lung during acute endotoxemia. J Leukoc Biol. 1994 ;56(6):759-768.
  • Arkovitz MS, Wispe JR, Garcia VF, et al. Selective inhibition of the inducible isoform of nitric oxide synthase prevents pulmonary transvascular flux during acute endotoxemia. J Pediatr Surg. 1996 ;31(8):1009-1015
  • Cuzzocrea S, Zingarelli B, Gilad E, et al: Protective effects of 3-aminobenzamide, an inhibitor of poly(ADP-ribose) synthetase in a carrageenan-induced model of local inflammation. Eur J Pharmacol. 1998 .19;342(1):67-76.
  • Artigas A, Bernard GR, Carlet J, et al . The American-European Consensus Conference on ARDS. Part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome. Am J Respir Crit Care Med 1998; 157: 1332-1347.
  • Szabo, C., L. H. Lim, S. Cuzzocrea, S, et al. Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts antiinflammatory effects. J Exp Med 1997; 186: 1041-1049
  • Shimado K, Murakami K, Enkhbaatar P, et al. Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep. Am J Physiol Lung Cell Mol Physiol 2003; 285: 240-249.
  • Kiefmann R, Heckel K, Dörger M, et al. Role of poly(ADP-ribose) synthetase in pulmonary leukocyte recruitment. Am J Physiol Lung Cell Mol Physiol 2003; 285: 996-1005. Postal Adress: Dr. Koray Topgül
  • OMÜ Tıp Fakültesi Genel Cerrahi AD
  • SAMSUN/ TURKEY
  • Tel : 362 4576 000-3674 Fax : 362 4576 041
  • E-mail : korayt@omu.edu.tr

Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir

Yıl 2005, Cilt: 12 Sayı: 2, 63 - 66, 01.04.2005

Öz

Amaç: Endotoksine bağlı endotoksemi geliştirilen üç gruba ayrılmış 21 erkek Wistar ratta (250-300g) PARS (poli ADPriboz sentetaz) inhibitörü 3-aminobenzamidin akciğer hasarı üzerine etkisi araştırıldı. Gereç ve Yöntem: Kontrol grubuna intraperitoneal olarak salin (1ml kg-1 n=7); ikinci gruba, intraperitoneal endotoksin (Escherichia coli lipopolysaccharide 055:B5 10 mg kg-1 :n=7); üçüncü gruba ise, endotoksinden 10 dakika önce olmak üzere intraperitoneal 3-aminobenzamid 10mg kg-1 ve 1 ml kg-1 salin uygulandı (n=7). Altı saat sonra fareler yüksek doz anestezik madde verilerek sakrifiye edildi. Protein konsantrasyonunu ve nötrofil sayımını yapmak için akciğer sağ lobuna bronkoalveolar lavaj (BAL) uygulandı. Sol lobun ise ıslak/kuru akciğer oranı hesaplandı. Sol akciğerin intravaskuler nötrofilleri salin ile yıkandı ve spektrofotometrik olarak myeloperoksidaz aktivitesi ölçüldü. İstatistiki değerlendirme için varyans analizi kullanıldı. Bulgular: Kontrol grubu ile karşılaştırıldığında, endotoksin verilen grupta ortalama pulmoner myeloperoksidaz aktivitesinin, ortalama BAL nötrofil konsantrasyonlarının ve protein ve damar dışı akciğer sıvısının sızıntısının işareti olan ortalama ıslak/kuru akciğer oranı anlamlı şekilde artmış olduğu görüldü. Artmış olarak bulunan bu değerler açısından, endotoksin + 3-aminobenzamid grubunda anlamlı bir fark bulunamadı. Sonuç: Bu çalışmanın sonuçları, endotokseminin belirgin bir şekilde akciğer hasarıyla gittiği ve inflamasyonun olduğu alanda PARS'ın etkisi ile nötrofillerin toplanmasında düşüşün ve bununda gelişen hasarla ilişkili olabileceğini göstermiştir. Anahtar kelimeler: Sepsis, 3-aminobenzamid, Akciğer hasarı.

Kaynakça

  • Altuntaş Y, Köksal G M, Sayılgan C, et al. Tavşanlarda oluşturulan intraabdominal SIRS modelinde erken dönemde oluşan değişikliklerin araştırılması. Göğüs Kalp Damar Anestezi ve Yoğun Bakım Derneği Dergisi 2003; 9: 4-10.
  • Bone RC. The pathogenesis of sepsis. Ann Intern Med 1991; 115: 457 – 469.
  • Wolfe TA, Dasta JF. Use of nitric oxide synthase inhibitors as a novel treatment for septic shock. Ann Pharmacother 1995; 29: 36 – 46.
  • Mercer DW, Smith GS, Cross JM, et al. Effect of Lipopolisaccharide on intestinal injury: Potential role of nitric oxide and lipid peroxidation. J Surg Res 1996; 63: 185 - 92.
  • Oliver FJ, Menissier-de Murcia J, Nacci C, et al. Resistance to endotoxic shock as a consequence of defective NF-kappaB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J 1999; 18: 4446-4454
  • Szabo C, Zingarelli B, Salzman AL. Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite. Circ Res 1996; 78: 1051 – 1063.
  • Szabo C. DNA strand breakage and activation of poly-ADP ribosyltransferase: A cytotoxic pathway triggered by peroxynitrite. Free Rad Biol Med 1996; 21: 855 –869.
  • Farivar AS, Woolley SM, Fraga CH,et al. Intratracheal poly (ADP) ribose synthetase inhibition ameliorates lung ischemia reperfusion injury. Ann Thorac Surg 2004 ;77(6):1938- 1943.
  • Bowes J, McDonald MC, Piper J, et al. Inhibitors of poly (ADP-ribose) synthetase protect rat cardiomyocytes against oxidant stress. Cardiovasc Res 1999; 41: 126 – 134.
  • Cuzzocrea S, Zingarelli B, Costantino G, Sottile A, Teti D, Caputi AP. Protective effect of poly(ADP-ribose) synthetase inhibition on multiple organ failure after zymosan- induced peritonitis in the rat. Crit Care Med 1999; 27(8): 1517 – 1523.
  • Cuzzocrea S, Thiemermann C, Salvemini D, et al. Potential therapeutic effect of antioxidant therapy in shock and inflammation. Curr Med Chem. 2004 ;11(9):1147-1162.
  • 12-Virag L, Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 54: 375-429, 2002)
  • Szabo A, Salzman A L, Szabo C. Poly (ADP-Ribose) Synthetase activation mediates pulmonary microvascular and intestinal mucosal dysfunction in endotoxin shock. Life Sciences 1998; 63: 2133-2139.
  • Wizemann TM, Gardner CR, Laskin JD, et al. Production of nitric oxide and peroxynitrite in the lung during acute endotoxemia. J Leukoc Biol. 1994 ;56(6):759-768.
  • Arkovitz MS, Wispe JR, Garcia VF, et al. Selective inhibition of the inducible isoform of nitric oxide synthase prevents pulmonary transvascular flux during acute endotoxemia. J Pediatr Surg. 1996 ;31(8):1009-1015
  • Cuzzocrea S, Zingarelli B, Gilad E, et al: Protective effects of 3-aminobenzamide, an inhibitor of poly(ADP-ribose) synthetase in a carrageenan-induced model of local inflammation. Eur J Pharmacol. 1998 .19;342(1):67-76.
  • Artigas A, Bernard GR, Carlet J, et al . The American-European Consensus Conference on ARDS. Part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome. Am J Respir Crit Care Med 1998; 157: 1332-1347.
  • Szabo, C., L. H. Lim, S. Cuzzocrea, S, et al. Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts antiinflammatory effects. J Exp Med 1997; 186: 1041-1049
  • Shimado K, Murakami K, Enkhbaatar P, et al. Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep. Am J Physiol Lung Cell Mol Physiol 2003; 285: 240-249.
  • Kiefmann R, Heckel K, Dörger M, et al. Role of poly(ADP-ribose) synthetase in pulmonary leukocyte recruitment. Am J Physiol Lung Cell Mol Physiol 2003; 285: 996-1005. Postal Adress: Dr. Koray Topgül
  • OMÜ Tıp Fakültesi Genel Cerrahi AD
  • SAMSUN/ TURKEY
  • Tel : 362 4576 000-3674 Fax : 362 4576 041
  • E-mail : korayt@omu.edu.tr
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Makaleler
Yazarlar

A.şükrü Taner Bu kişi benim

Koray Topgül Bu kişi benim

Fikri Küçükel Bu kişi benim

Hilal Özer Bu kişi benim

Selim Temel Bu kişi benim

Yayımlanma Tarihi 1 Nisan 2005
Yayımlandığı Sayı Yıl 2005 Cilt: 12 Sayı: 2

Kaynak Göster

APA Taner, A., Topgül, K., Küçükel, F., Özer, H., vd. (2005). Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir. Journal of Turgut Ozal Medical Center, 12(2), 63-66.
AMA Taner A, Topgül K, Küçükel F, Özer H, Temel S. Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir. J Turgut Ozal Med Cent. Nisan 2005;12(2):63-66.
Chicago Taner, A.şükrü, Koray Topgül, Fikri Küçükel, Hilal Özer, ve Selim Temel. “Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir”. Journal of Turgut Ozal Medical Center 12, sy. 2 (Nisan 2005): 63-66.
EndNote Taner A, Topgül K, Küçükel F, Özer H, Temel S (01 Nisan 2005) Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir. Journal of Turgut Ozal Medical Center 12 2 63–66.
IEEE A. Taner, K. Topgül, F. Küçükel, H. Özer, ve S. Temel, “Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir”, J Turgut Ozal Med Cent, c. 12, sy. 2, ss. 63–66, 2005.
ISNAD Taner, A.şükrü vd. “Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir”. Journal of Turgut Ozal Medical Center 12/2 (Nisan 2005), 63-66.
JAMA Taner A, Topgül K, Küçükel F, Özer H, Temel S. Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir. J Turgut Ozal Med Cent. 2005;12:63–66.
MLA Taner, A.şükrü vd. “Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir”. Journal of Turgut Ozal Medical Center, c. 12, sy. 2, 2005, ss. 63-66.
Vancouver Taner A, Topgül K, Küçükel F, Özer H, Temel S. Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir. J Turgut Ozal Med Cent. 2005;12(2):63-6.