title: (5R)-5-hydroxytriptolide (LLDT-8) protects against bleomycin-induced lung fibrosis in mice.
abstract: OBJECTIVE
  To study the protective effects of a triptolide-derived, novel compound, (5R)-5-hydroxytriptolide (LLDT-8), on bleomycin-induced lung fibrosis.
  
  
  METHODS
  C57BL/6 mice received an intratracheal injection of bleomycin and were then treated with LLDT-8 (0.5, 1, 2 mg/kg, ip) once daily for 7 or 14 consecutive days. The body weight loss and lung index augmentation was observed; the inflammatory response including differential cells counts of neutrophils, macrophages, and lymphocytes in the bronchoalveolar lavage fluid (BALF), superoxide dismutase (SOD), and malondialdehyde (MDA) level in the lung homogenates was detected, and the fibrosis extent was evaluated by hydroxyproline content and histopathological changes in the lungs. In addition, the pro-inflammatory and pro-fibrotic cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), and transforming growth factor-alpha (TGF-alpha) production in the lungs were measured.
  
  
  RESULTS
  LLDT-8 alleviated the body weight loss and lung index increase caused by bleomycin, reduced neutrophils and lymphocytes in the BALF, promoted SOD activity, decreased MDA production, and inhibited the hydroxyproline level and the amelioration of lung tissue histological damage. Moreover, LLDT-8 suppressed TNF-alpha, IL-4, and TGF-beta production in the lung homogenates.
  
  
  CONCLUSIONS
  LLDT-8 showed protective effects against bleomycin-induced lung fibrosis, and the results suggested the potential role of LLDT-8 in the treatment of this disease.
authors: Laboratory of Immunopharmacology and Laboratory of Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203 China.
authors: Yong-xin
authors: YX
authors: Ren
authors: Ru
authors: R
authors: Zhou
authors: Wei
authors: W
authors: Tang
authors: Wen-hai
authors: WH
authors: Wang
authors: Yuan-chao
authors: YC
authors: Li
authors: Yi-fu
authors: YF
authors: Yang
authors: Jian-ping
authors: JP
authors: Zuo
mesh_terms: D000818:Animals; D000963:Antimetabolites; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000096:biosynthesis
chemical_list: C509074:5-hydroxytriptolide; D000963:Antimetabolites; D016207:Cytokines; D004224:Diterpenes; D020011:Protective Agents; D001761:Bleomycin; D013482:Superoxide Dismutase