Protective effects of curcumin against amiodarone-induced pulmonary fibrosis in rats.
(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.
Punithavathi
Durairaj
D
Department of Biotechnology, Central Leather Research Institute, Chennai (Madras), India. vnar12@yahoo.com
Venkatesan
Narayanan
N
Babu
Mary
M
D000638:Amiodarone; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D024042:Collagen Type I / Q000096:biosynthesis / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007322:Instillation, Drug; D007441:Intubation, Gastrointestinal; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014132:Trachea; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D015854:Up-Regulation
D024042:Collagen Type I; D008070:Lipopolysaccharides; D016755:Proto-Oncogene Proteins c-jun; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D003474:Curcumin; D000638:Amiodarone