Inhibitory effect of acetamide-45 on airway inflammation and phosphodiesterase 4 in allergic rats.
OBJECTIVE
To determine the effects of acetamide-45 on respiratory function, airway inflammation, and the activity of phosphodiesterase 4 (PDE4) in allergic rats.


METHODS
Rats were sensitized by a single intramuscular injection with ovalbumin (OVA) and were challenged with ovalbumin applied by using an aerosol repeatedly for 7 d after 2 weeks. Acetamide-45 at concentrations of 5, 10, or 30 mg/kg was then administered by intraperitoneal injection. Changes in dynamic lung compliance and lung resistance, the accumulation of inflammatory cells in bronchoalveolar lavage, PDE4 activity, and the concentration of interleukin-4 in rat lung tissue were determined.


RESULTS
Seven days of treatment with acetamide-45 prevented eosinophil accumulation in allergic rats. At doses of 5, 10, and 30 mg/kg, acetamide-45 decreased lung resistance to 0.20+/-0.04, 0.25+/-0.07, and 0.22+/-0.05 cmH2O.s(-1).mL(-1), respectively (P<0.05 vs OVA), and it also increased dynamic lung compliance to 0.41+/-0.07, 0.39+/-0.06, and 0.42+/-0.09 mL/cmH2O (P<0.05 vs OVA). After being treated with different doses of acetamide-45, the PDE4 activities in lung tissue were 281+/-55, 273+/-57, and 238+/-36 nmol.g(-1).min( -1) (P<0.05 vs OVA), and the concentrations of interleukin-4 in lung tissue were 6.22+/-1.13, 5.95+/-1.20, and 5.68+/-2.20 microg/protein (P<0.05 vs OVA).


CONCLUSIONS
Acetamide-45 was found to improve respiratory function and inhibit airway inflammation in this animal model, and the PDE4 activity of lung tissue was obviously inhibited. Acetamide-45 was an effective anti-inflammatory agent in respiratory inflammation, and the mechanism of its action might depend on inhibition of PDE4.
Wang
Kai
K
Respiratory Department, Second Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310009, China.
Shen
Hua-Hao
HH
Chen
Jun-Chun
JC
Chen
Zhong
Z
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology*; D000403:Airway Resistance; D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004804:Eosinophils / Q000473:pathology; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000378:metabolism; D008170:Lung Compliance; D008297:Male; D015394:Molecular Structure; D010047:Ovalbumin; D051381:Rats; D017207:Rats, Sprague-Dawley
D000081:Acetamides; D018926:Anti-Allergic Agents; D007211:Indoles; C522433:acetamide 45; D015847:Interleukin-4; D010047:Ovalbumin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4