To determine the effects of acetamide-45 on respiratory function, airway inflammation, and the activity of phosphodiesterase 4 (PDE4) in allergic rats.
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.
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 μg/g protein (P<0.05 vs OVA).
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.
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Project supported by Science and Technology department of Zhejiang province (No 2003C24002).
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Wang, K., Shen, Hh., Chen, Jc. et al. Inhibitory effect of acetamide-45 on airway inflammation and phosphodiesterase 4 in allergic rats. Acta Pharmacol Sin 26, 1492–1496 (2005). https://doi.org/10.1111/j.1745-7254.2005.00227.x
- 3′,5′-cyclic nucleotide phosphodiesterase
- respiratory function tests
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