Protective effects of curcumin against amiodarone‐induced pulmonary fibrosis in rats

We have studied whether curcumin prevents amiodarone‐induced lung fibrosis in rats. Intratracheal instillation of amiodarone (6.25 mg kg −1 on days 0 and 2, and then killed on day 3, day 5, week 1, week 3 and week 5 after amiodarone administration) induced increases in total protein and lactate dehydrogenase (LDH) activity on days 3 and 5 in bronchoalveolar lavage fluid (BALF). Total cell counts, alveolar macrophages, neutrophils and eosinophils recovered by BAL, and lung myeloperoxidase (MPO) activity were significantly higher in amiodarone rats. Tumor necrosis factor‐ α (TNF‐ α ) release after lipopolysaccharide (LPS) stimulation and superoxide anion generation after phorbol myristate acetate (PMA) stimulation were higher in the alveolar macrophages of amiodarone rats at 3 and 5 weeks postamiodarone instillation than in controls. Amiodarone also induced increases in transforming growth factor‐ β 1 (TGF‐ β 1) expression, collagen deposition, type I collagen expression and c‐Jun protein in lungs. Curcumin (200 mg kg −1 body weight after first amiodarone instillation and daily thereafter for 5 weeks)‐treated amiodarone rats had reduced levels of protein, LDH activity, total cell numbers and differential cell counts in BALF. LPS‐stimulated TNF‐ α release and PMA‐stimulated superoxide generation were significantly suppressed by curcumin. Furthermore, curcumin inhibited the increases in lung MPO activity, TGF‐ β 1 expression, lung hydroxyproline content, expression of type I collagen and c‐Jun protein in amiodarone rats. Our results have important implications for the treatment of amiodarone‐induced lung fibrosis. British Journal of Pharmacology (2003) 139 , 1342–1350. doi: 10.1038/sj.bjp.0705362