Histopathological evaluation of induced pulmonary fibrosis under the effect of montelukast


  • Mohammed Rabah Mahdi Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Iraq
  • Wassan Abdul Kareem Abbas Department of Clinical Laboratory Science, College of Pharmacy, Mustansiriyah University, Iraq
  • Ghaith Ali Jasim Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Iraq




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


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.


- Parimon T., Yao C., Stripp B. R., Noble P. W., and Chen P.Alveolar epithelial type II cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis, Int. J. Mol. Sci. 2020. vol. 21. no. 7. Pp: 2269.

- Wuyts W. A. et al. The pathogenesis of pulmonary fibrosis: a moving target, Eur. Respir. J. 2013.vol. 41, no. 5 Pp: 1207–1218.

- Galli J. A., Pandya A., Vega‐Olivo M., Dass C., Zhao H., and Criner G. J. Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: tolerability and adverse drug reactions, Respirology. 2017.vol. 22. no. 6. Pp: 1171–1178.

- Tawfeeq Y., Mohammed A. A., and Kamal Y. M. The Intervention of the Pirfenidone with Pericyst Layer Building of the Hydatid Cyst, Syst. Rev. Pharm. 2020.vol. 11. no. 9. Pp: 1091–1099.

- Knüppel L. et al. A novel antifibrotic mechanism of nintedanib and pirfenidone. Inhibition of collagen fibril assembly, Am. J. Respir. Cell Mol. Biol. 2017.vol. 57. no. 1. Pp: 77–90 .

- Varone F., Sgalla G., Iovene B., Bruni T., and Richeldi L. Nintedanib for the treatment of idiopathic pulmonary fibrosis,” Expert Opin. Pharmacother. 2018.vol. 19. no. 2. Pp: 167–175.

- Wollin L. et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis, Eur. Respir. J. 2015. vol. 45. no. 5. Pp: 1434–1445.

- Salih A. G., Al-shamma K. J., Hassan M. M., Salman R. Y., and Salih I. M. Treatment options of acute viral bronchiolitis in two Iraqi pediatric hospitals with a recent montelukast treatment option., Al Mustansiriyah J. Pharm. Sci. 2013.vol. 13. no. 2. Pp: 87–94, , doi: 10.32947/ajps.v13i2.206.

- Tintinger G. R., Feldman C., Theron A. J., and Anderson R. ontelukast: more than a cysteinyl leukotriene receptor antagonist?, ScientificWorldJournal. 2010.vol. 10. Pp: 2403–2413.

- Wu Y. et al.Montelukast, cysteinyl leukotriene receptor 1 antagonist, inhibits cardiac fibrosis by activating APJ,Eur. J. Pharmacol. 2022.vol. 923. Pp: 174892.

- Saeed M. F. , Alabbassi G. M., and Al-Ezzi I. M. Protective Effect of Co Q10 and Candesartan on Bleomyycin Induced Lung Fibrosis in Rats,Al Mustansiriyah J. Pharm. Sci. 2021.vol. 21. no. SI. Pp: 3.

- Topaloğlu N. et al.Protective effect of cysteinyl leukotriene receptor antagonist montelukast in bleomycin-induced pulmonary fibrosis, Turkish J. Thorac. Cardiovasc. Surg. 2018.vol. 26. no. 4. Pp: 588.

- Song X., Yu W., and Guo F.Pirfenidone suppresses bleomycin‑induced pulmonary fibrosis and periostin expression in rats,Exp. Ther. Med. 2018. vol. 16. no. 3. Pp: 1800–1806, , doi: 10.3892/etm.2018.6378.

- Samareh Fekri M. et al.Protective effect of standardized extract of Myrtus communis L.(myrtle) on experimentally bleomycin-induced pulmonary fibrosis: biochemical and histopathological study, Drug Chem. Toxicol. 2018.vol. 41. no. 4. Pp: 408–414.

- Hashimoto N. et al.Endothelial–mesenchymal transition in bleomycin-induced pulmonary fibrosis,Am. J. Respir. Cell Mol. Biol. 2010. vol. 43. no. 2. Pp: 161–172.

- Yasui H. et al.Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse,Am. J. Respir. Crit. Care Med. 2001.vol. 163. no. 7. Pp: 1660–1668,.

- Guo J., Yang Z., Jia Q., Bo C., Shao H., and Zhang Z.Pirfenidone inhibits epithelial-mesenchymal transition and pulmonary fibrosis in the rat silicosis model,Toxicol. Lett. 2019.vol. 300. Pp: 59–66.

- Dewage S. N. V. et al.The efficacy of pirfenidone in a sheep model of pulmonary fibrosis, Exp. Lung Res. 2019. vol. 45. no. 9–10. Pp: 310–322.

- Tokat A. O. et al.Montelukast attenuates radioactive I131-induced pulmonary damage on rats, Int. J. Radiat. Biol. 2018.vol. 94. no. 6. Pp: 542–550.

- Shaker O. G. and Sourour D. A.Effect of leukotriene receptor antagonists on lung fibrosis in rats, J. Appl. Toxicol. 2011.vol. 31. no. 7. Pp: 678–684.