Inhibitory effect of acetamide-45 on airway inflammation and phosphodiesterase 4 in allergic rats
Abstract
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 0.20plusminus0.04, 0.25plusminus0.07, and 0.22plusminus0.05 cmH2Odots-1dotmL-1, respectively (P<0.05 vs OVA), and it also increased dynamic lung compliance to 0.41plusminus0.07, 0.39plusminus0.06, and 0.42plusminus0.09 mL/cmH2O (P<0.05 vs OVA). After being treated with different doses of acetamide-45, the PDE4 activities in lung tissue were 281plusminus55, 273plusminus57, and 238plusminus36 nmoldotg-1dotmin-1 (P<0.05 vs OVA), and the concentrations of interleukin-4 in lung tissue were 6.22plusminus1.13, 5.95plusminus1.20, and 5.68plusminus2.20 mug/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.
Keywords:
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 0.20plusminus0.04, 0.25plusminus0.07, and 0.22plusminus0.05 cmH2Odots-1dotmL-1, respectively (P<0.05 vs OVA), and it also increased dynamic lung compliance to 0.41plusminus0.07, 0.39plusminus0.06, and 0.42plusminus0.09 mL/cmH2O (P<0.05 vs OVA). After being treated with different doses of acetamide-45, the PDE4 activities in lung tissue were 281plusminus55, 273plusminus57, and 238plusminus36 nmoldotg-1dotmin-1 (P<0.05 vs OVA), and the concentrations of interleukin-4 in lung tissue were 6.22plusminus1.13, 5.95plusminus1.20, and 5.68plusminus2.20 mug/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.