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

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Abstract
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‐β1 (TGF‐β1) 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‐β1 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

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