Potential effects of peroxisome proliferator-activated receptor activator on LPS-induced lung injury in rats

Multiple factors contribute to the pathogenesis and prognosis of chronic obstructive pulmonary disease (COPD), still requiring new therapeutic strategies and medications for the disease. The aim of the present study is to investigate the model of lipopolysaccharide (LPS)-induced chronic lung injury and hyperinflation and test therapeutic effects of peroxisome proliferator-activated receptor (PPAR)-gamma agonist. Wister rats were challenged with intra-tracheal instillation of LPS at concentrations of 0.006, 0.060, 0.600, and 6.000 mg/ml per kg, twice a week, for 1, 2, 4 and 6 weeks. PPAR activator, 15-deoxy-Delta(12,14)-prostaglandin J2 (15D-PGJ2), or vehicle (PBS) was administered orally and daily at the dose of 1 and 10 mg/ml per kg in animals challenged with LPS or PBS at the dose of 0.060 mg/ml per kg body weight twice a week for 4 weeks. We found that intra-tracheal exposure of LPS resulted in a dose-dependent pattern of chronic lung hyperinflation and hypertrophy, increased alveolar enlargement, reduced vascular endothelial growth factor (VEGF) and elevated tissue inhibitor of metalloproteinases (TIMP)-1 levels in bronchoalveolar lavage (BAL) fluid, and early changes of leukocyte influx and interferon (IFN)-gamma levels in bronchoalveolar lavage (BAL) fluid. PPAR-gamma agonist ameliorated these changes related with the dose used. LPS-induced lung disease model shows some similarities with human disease, and PPAR-gamma agonist may be an alternative for COPD therapy. (C) 2009 Elsevier Ltd. All rights reserved.