title: Therapeutic effects of pyrrolidine dithiocarbamate on acute lung injury in rabbits.
abstract: BACKGROUND
  Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is an early characteristic of multiple organ dysfunction, responsible for high mortality and poor prognosis in patients. The present study aims to evaluate therapeutic effects and mechanisms of pyrrolidine dithiocarbamate (PDTC) on ALI.
  
  
  METHODS
  Alveolar-arterial oxygen difference, lung tissue edema and compromise, NF-κB activation in polymorphonuclear neutrophil (PMN), and systemic levels of tumor necrosis factor-alpha (TNFa) and intercellular adhesion molecule-1 (ICAM-1) in rabbits induced by the intravenous administration of lipopolysaccharide (LPS) and treated with PDTC. Production of TNFa and IL-8, activation of Cathepsin G, and PMNs adhesion were also measured.
  
  
  RESULTS
  The intravenous administration of PDTC had partial therapeutic effects on endotoxemia-induced lung tissue edema and damage, neutrophil influx to the lung, alveolar-capillary barrier dysfunction, and high systemic levels of TNFa and ICAM-1 as well as over-activation of NF-κB. PDTC could directly and partially inhibit LPS-induced TNFa hyper-production and over-activities of Cathepsin G. Such inhibitory effects of PDTC were related to the various stimuli and enhanced through combination with PI3K inhibitor.
  
  
  CONCLUSIONS
  NF-κB signal pathway could be one of targeting molecules and the combination with other signal pathway inhibitors may be an alternative of therapeutic strategies for ALI/ARDS.
authors.affiliation: Department of Emergency Medicine, The Second Military University Changhai Hospital, China.
authors.forename: Meitang
authors.initials: M
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Dian
authors.initials: D
authors.lastname: Wang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: He
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002196:Capillaries / Q000187:drug effects; D056649:Cathepsin G / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C020972:pyrrolidine dithiocarbamic acid; D056649:Cathepsin G; D010100:Oxygen