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

被引:86
作者
Punithavathi, D
Venkatesan, N
Babu, M
机构
[1] Cent Leather Res Inst, Dept Biotechnol, Madras 600020, Tamil Nadu, India
[2] Cent Leather Res Inst, Dept Biochem, Madras 600020, Tamil Nadu, India
关键词
amiodarone; collagen; curcumin; superoxide anion; tumor necrosis factor-alpha;
D O I
10.1038/sj.bjp.0705362
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 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. 2 Tumor necrosis factor-alpha (TNF-alpha) 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-beta1 (TGF-beta1) expression, collagen deposition, type I collagen expression and c-Jun protein in lungs. 3 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-alpha release and PMA-stimulated superoxide generation were significantly suppressed by curcumin. Furthermore, curcumin inhibited the increases in lung MPO activity, TGF-beta1 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.
引用
收藏
页码:1342 / 1350
页数:9
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