The Possible Protective Effects of Zileuton against Pulmonary Fibrosis Induced by Amiodarone in Male Rats

Abstract

Introduction

Pulmonary fibrosis is characterized by cellular alteration of the alveolar region with lung inflammation. Leukotrienes play an important role in the progression of the disease. This study was designed to investigate the possible protective effect of zileuton against amiodarone-induced pulmonary fibrosis in male rats.

Materials and methods

Pulmonary fibrosis was induced by administering amiodarone (100 mg/kg intraperitoneally i.p) and concomitantly treated with zileuton (30 mg/kg intraperitoneally i.p) for 15 days in wistar albino male rats. Biochemical parameters include TNF-?, IL-1?, 5-lipoxygenase; MDA and GSH in lung tissue were estimated, as well as lung histological studies.

Results

In rats treated with amiodarone, levels of TNF-?, IL-1?, 5-lipoxygenase and MDA were significantly elevated (p<0.05) with reduction in GSH level when compared with those treated with saline only. Meanwhile; administration of zileuton in group 3 was concerned with significant (p<0.05) improvement in the biochemical parameters when compared with group 1 and 2.  Furthermore, zileuton histologically reduced the number of inflammatory cells and ameliorate the destruction of lung architecture and pulmonary fibrosis induced by amiodarone.

Conclusion

Zileuton ameliorate pulmonary fibrosis induced by amiodarone in male rats, by inhibiting 5-lipoxygenase activity and reducing leukotrienes synthesis.

Keywords: Zileuton, pulmonary fibrosis, amiodarone, rats.