Histopathological evaluation of induced pulmonary fibrosis under the effect of montelukast

Abstract

Pulmonary fibrosis (PF) is an interstitial lung disease leading to scarring of the lung. There are several types of lung fibrosis as familial pulmonary fibrosis, idiopathic pulmonary fibrosis, and others associated with non-specific interstitial pneumonia. The most common type is idiopathic pulmonary fibrosis which is an unknown cause. Lung fibrosis causes changes in the histology of the lung by the disappearance of the lung parenchyma, replaced by an inflammatory infiltrate, and mild thickening of the pulmonary artery. The management of pulmonary fibrosis included Azathioprine, corticosteroid, and N-acetyl cysteinyl in 2011 but in 2014 this guideline was removed and replaced by nintedanib and pirfenidone. This study used Pirfenidone, as standard therapy for the treatment of pulmonary fibrosis, and montelukast is Cysteinyl leukotrienes (CysLT) antagonist which binds to its receptor (CysLTE4) located on smooth muscle cells of the respiratory airway causing anti-inflammatory effect by inhibition of inflammatory markers as TGFβ1. Sixty male rats were divided into five groups,12 rats for each group where the control group received distilled water by gastric gavage, the induction group received bleomycin intratracheally as a single dose, the pirfenidone group received pirfenidone 50mg/kg, montelukast group received montelukast 20mg/kg and the combination group received a half dose of pirfenidone and montelukast. After twenty-eight days after the treatment with montelukast or pirfenidone sacrifice rats and collect the organ (lungs) from each group were then placed in buffer formalin 10% for histopathological study. After 14 days from bleomycin dose, results show that bleomycin cause massive disappearance of pulmonary parenchyma that was replaced by an inflammatory infiltrate and medial thickening of the pulmonary artery in all groups, but montelukast and pirfenidone show normal lung paranchyma and pulmonary artery after 28 days of treatment in pirfenidone, montelukast, and combination groups. In conclusion, that bleomycin changes the histology of the lung causing induction of lung fibrosis in all groups after 14 days except control group but pirfenidone, montelukast, and combination of half dose of pirfenidone with a half dose of montelukast return the lung to normal architecture after 28 days of treatment.

Keywords

• pulmonary fibrosis, materials and methods, results, and discussion.