Inhibitory effect of acetamide‐45 on airway inflammation and phosphodiesterase 4 in allergic rats 1

Aim: 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 cmH 2 O·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/cmH 2 O ( 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 μg/g 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.