Therapeutic effects of pyrrolidine dithiocarbamate on acute lung injury in rabbits

Journal of Translational Medicine

Research

Jian He¹  Tao Liu¹  Meitang Wang¹  Yonghua Zheng²  Xiangdong Wang²  Dian Wang² 

[1] Department of Emergency Medicine, The Second Military University Changhai Hospital, China;Department of Respiratory Medicine and Biomedical Research Center, Fudan University Zhongshan Hospital, Shanghai, China;

关键词: acute lung injury;    TNF-α;    ICAM-1;    NF-κB;    pyrrolidine dithiocarbamate;   

DOI  :  10.1186/1479-5876-9-61

 received in 2011-01-29, accepted in 2011-05-13,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundAcute 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.MethodsAlveolar-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.ResultsThe 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.ConclusionNF-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.

【 授权许可】

CC BY   
© Wang et al; licensee BioMed Central Ltd. 2011