Anti- Allergic Effect of Sildenafil and Tadalafil in Ovalbumin Induced Bronchial Asthma in Rats
Author(s): Vijayalaxmi, Rachna Gupta, Kavita Gulati, Arunabha Ray
Background: Cyclic nucleotides (cAMP and cGMP) act as secondary messengers in various cellular processes like signal transduction and inflammation. Sildenafil and tadalafil are phosphodiesterases-5 (PDE-5) inhibitors which prevent the degradation of these cyclic nucleotides and thus play a key role in regulating allergy, inflammation, and smooth muscle relaxation. The present study was conducted to ascertain the anti-allergic potential of Phosphodiesterase-5 inhibitors, sildenafil and tadalafil. Their effects on mast cell degranulation in animal model of bronchial asthma was explored.
Method: An allergic model of bronchial asthma was developed. Wistar rats were first sensitized with 10 mg intraperitoneal (ip) ovalbumin adsorbed to 10 µg of aluminum hydroxide on day 0 and were subsequently divided into six groups (n=6). Animals received the following treatment: sildenafil (1 and 3 mg/kg ip) and tadalafil (1 and 3 mg/kg ip), normal saline (2 ml/kg ip) and prednisolone (5 mg/kg ip) from day 1 to day 14. On day 14 animals were challenged with ovalbumin (1 mg ip). After 24 h (on day 15) of antigen challenge all animals were anaesthetized with halothane for terminal sacrifice. The mesentery was harvested and stained with 0.2% toludine blue. The degree of mast cell degranulation was assessed in different treatment groups.
Results: Significant reductions in the percentage of degranulated mast cells in rat mesentery were observed in groups which received pre-treatment with sildenafil (1 and 3 mg/kg ip) and tadalafil (1 and 3 mg/kg ip). Both, sildenafil and tadalafil demonstrated a dose dependent response. Tadalafil caused greater inhibition of mast cells’ degranulation as compared to sildenafil.
Conclusion: Sildenafil and tadalafil decreased mast cell degranulation in rat mesentery preparation. Both sildenafil and tadalafil exhibited dose dependent response. Tadalafil was more potent than sildenafil in inhibiting mast cell degranulation. Hence, these drugs could have a therapeutic potential in bronchial asthma.