Zl-n-91, a selective phosphodiesterase 4 inhibitor, suppresses inflammatory response in a COPD-like rat model.
Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by poorly reversible airflow limitation induced by cigarette smoking and/or other noxious particle and gases. Phosphodiesterase (PDE) 4 inhibitors are known to elevated cAMP concentrations in inflammatory cells, leading to inhibition of inflammatory response, relaxation of smooth muscle in the airway, and modulation of sensory nerves in the lung as well. To investigate whether Zl-n-91, a new selective PDE4 inhibitor, could decrease inflammation and improve lung function in a COPD-like rat model, male Sprague-Dawley rats are used to challenge with lipopolysaccharide (LPS) and cigarette smoking (CS) exposure to induce COPD-like animal model. Administration of Zl-n-91 at different dosages results in decreases of inflammatory cell in bronchoalveolar lavage fluid (BALF) as compared with vehicle treatment. Zl-n-91 at 0.03, 0.3 or 3mg/kg not only dose-dependently inhibited PDE4 activity, but also decreased MMP-9 level in lungs and improved dynamic compliance (C(dyn)) as compared with vehicle treatment. Therefore, Zl-n-91 could inhibit inflammatory responses in rats after cigarette smoking exposure and LPS challenge, and it could be of some therapeutic potential as an alternative medicine in treatment of pulmonary diseases such as COPD.
Wang
Ya-juan
YJ
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, College of Medicine, Zhejiang University, Hangzhou 310058, China.
Jiang
Ya-li
YL
Tang
Hui-fang
HF
Zhao
Chun-zhen
CZ
Chen
Ji-qiang
JQ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000276:immunology; D004195:Disease Models, Animal; D005663:Furans / Q000737:chemistry / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D061965:Matrix Metalloproteinase Inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009195:Peroxidase / Q000187:drug effects / Q000276:immunology; D010647:Phenyl Ethers / Q000737:chemistry / Q000627:therapeutic use*; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005663:Furans; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D010647:Phenyl Ethers; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; C548712:Zl-n-91 compound; D009195:Peroxidase; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020780:Matrix Metalloproteinase 9