The Effect of Cigarette Smoke in Bleomicyn Induced Pulmonary Fibrosis in the Rat Model

Abstract

The role of cigarette smoking in the development and outcome of pulmonary fibrosis is uncertain. In this study, we aimed to assess the effect of route of bleomycin exposure in the development of pulmonary fibrosis and the effects of cigarette smoke on bleomycin-induced lung fibrosis. We studied five groups of rats; 1-control group, 2-intratracheal bleomycin (IT), 3-intratracheal bleomycin plus cigarette smoke for 4 wk (IT-S), 4-inhaled bleomycin (IN), 5-inhaled bleomycin plus cigarette smoke for 4 wk (IN-S). According to Aschoft's criteria, fibrosis score was higher in IT and IT-S compared to control, IN and IN-S groups. There was no significant difference between IT and IT-S groups. Histopathological evaluation of the lungs of rats revealed that neutrophils, macrophages, plasma cells and lymphocytes in alveolar interstitial space were significantly higher in IT and IT-S compared to IN and IN-S (p< 0.001). IT and IT-S showed a severe collagen, laminin, elastin, fibronectin and proteoglican levels in alveolar, vascular, airway and interstitial space. IN and IN-S showed mild inflammation in lung. There were alveolitis, edema, peribronchial fibrosis, fibroblast proliferation and emphysematous lesions in all groups except for the control group. In this study, we showed that in the development of pulmonary fibrosis in rats, intratracheal administration of bleomycin is more effective than bleomycin inhalation and smoking has no additional effect on development of fibrosis. Keywords: Bleomycin, Pulmonary fibrosis, Cigarette smoking ÖZET S›çan Modelinde Bleomisine Ba¤l› Pulmoner Fibroziste Sigara Duman›n›n EtkisiSigaran›n pulmoner fibrozis geliflimindeki ve sonuçlar›na etkisi net de¤ildir. Bu çal›flmada bleomisin uygulama yolunun pulmoner fibrosis geliflimine ve sigaran›n bleomisine ba¤l› pulmoner fibrosis geliflimi üzerine etkisini de¤erlendirmeyi amaçlad›k. Befl grup fare ile çal›flt›k; 1-kontrol grubu, 2-intratrakeal bleomisin (IT), 3-intratrakeal bleomisin ve 4 hafta süreyle sigara duman› (IT-S), 4-inhale bleomisin(IN), 5-4 hafta süreyle inhale bleomisinle birlikte sigara duman› (IN-S). Aschoft kriterlerine gö-re fibrosis skoru IT ve IT-S gruplar›nda kontrol, IN ve IN-S gruplar›yla karfl›laflt›r›ld›¤›nda daha yüksek bulundu. IT ve IT-S gruplar› aras›nda belirgin fark yoktu. Farelerin akci¤erlerinin histopatolojik incelemesinde alveol ve interstisyel boflluktaki nötrofil, makrofaj, plazma hücreleri ve lenfositler IN ve IN-S grubuna k›yasla IT ve IT-S grubunda belirgin olarak daha yüksekti (p<0.001). IT ve IT-S gruplar›nda alveolar, vasküler, havayolu ve interstisyel bofllukta yo¤un kollajen, laminin, elastin, fibronektin ve proteoglikan düzeyleri izlendi. IN ve IN-S gruplar›nda akci¤erde hafif inflamasyon izlendi. Kontrol grubu d›fl›nda tüm gruplarda alveolit, ödem, peribronflial fibrozis, fibroblast ço¤almas› ve amfizematöz lezyonlar mevcuttu. Bu çal›flmada farelerde pulmoner fibrozis oluflumunda intratrakeal bleomisin uygulaman›n inhale bleomisin inhalasyonundan daha etkili oldu¤u ve sigaran›n pulmoner fibr...