Amelioration of pulmonary dysfunction and neutrophilic inflammation by PPAR gamma agonist in LPS-exposed guinea pigs.
Airway dysfunction and pulmonary neutrophilic inflammation are the major characteristics of inflammatory conditions of lungs like chronic obstructive pulmonary disease (COPD). Lipopolysaccharide (LPS), a constituent of cigarette smoke, has been identified as the most important risk factor for COPD development. Inhalation exposure to LPS or cigarette smoke elicits an inflammatory response accompanied by airway hyperresponsiveness, elevated proinflammatory mediators and inflammatory cells similar to COPD. In the present study, we have evaluated the effects of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, in LPS-induced pulmonary dysfunction, inflammatory changes and oxidative stress in guinea pigs. Inhalation exposure to nebulised LPS (30 microg ml(-1)) resulted in significant increase in the breathing frequency and bronchoconstriction accompanied with a significant decrease in tidal volume. Our results demonstrated that the LPS-induced pulmonary dysfunction was temporally associated with neutrophil infiltration as evident from heavy neutrophilia, increased TNFalpha in bronchoalveolar lavage fluid (BAL), elevated myeloperoxidase (MPO) level and histology of the lung tissue. Exposure to LPS also produced significant increase in tissue malondialdehyde (MDA) level indicating underlying oxidative stress. The results also reveal that pioglitazone (3, 10 and 30 mg kg(-1), p.o.) is effective in abrogating the pulmonary dysfunction by attenuating neutrophilia, TNFalpha release and oxidative stress in LPS-induced model of acute lung inflammation. Results from the present study have added to the emergent body of evidence that PPAR gamma agonists are effective in the therapy of inflammatory disease of the lungs.
Sharma
Rohini
R
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar (Mohali), Punjab 160062, India.
Kaundal
Ravinder K
RK
Sharma
Shyam Sunder
SS
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D029968:Escherichia coli Proteins / Q000633:toxicity; D006168:Guinea Pigs; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008168:Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists*; D009195:Peroxidase / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D000077205:Pioglitazone; D010993:Plethysmography, Whole Body; D011014:Pneumonia / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D020889:Rolipram / Q000494:pharmacology; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D047495:PPAR gamma; D010726:Phosphodiesterase Inhibitors; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D009195:Peroxidase; D020889:Rolipram; D000077205:Pioglitazone