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. Tadal