Pars Inhibitor 3-Aminobenzamide Attenuates Lung Injury in Experimental Endotoxemia

Abstract

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

Keywords

• Sepsis, 3-Aminobenzamide, Pulmonary injury

Deneysel Endotoksemide Pars İnhibitörü 3-Aminobenzamid Akciğer Hasarini Azaltir

Abstract

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.

Keywords

• Sepsis, 3-aminobenzamid, Akciğer hasarı.

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