Inhibitory effects of sildenafil and tadalafil on inflammation, oxidative stress and nitrosative stress in animal model of bronchial asthma
Abstract
Background Cyclic neucleotides are involved in many cellular functions including smooth muscle relaxation, inflammation, and signal transduction. Sildenafil and tadalafil are phosphodiesterase-5 (PDE-5) inhibitors which prevent the degradation of cyclic neucleotide i.e. guanosine 3′,5′ cyclic monophosphate (cGMP) and increase the levels of cGMP. In this study sildenafil and tadalafil were evaluated for their anti-inflammatory, anti-oxidative and anti-nitrosative stress potential in animal model of bronchial asthma. Methods Wistar rats were sensitized with 10 mg intraperitoneal ( ip ) ovalbumin adsorbed to 10 μg of aluminum hydroxide on day 0. Animals were given sildenafil (1 and 3 mg/kg ip ) and tadalafil (1 and 3 mg/kg ip ) from day 1 to day 14. Also, on day 14 animals were challenged with ovalbumin (1 mg ip ). After 24 h, samples were collected to analyze interleukin-4 (IL-4) and tumour necrosis factor-α (TNF-α), in serum and bronchoalveolar lavage fluid (BALF). The oxidative stress markers malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide metabolites (NO_x) were also measured in serum. Results Pre-treatment with sildenafil (1 and 3 mg/kg ip ) and tadalafil (1 and 3 mg/kg ip ) significantly reduced the levels of pro-inflammatory cytokines IL-4 and TNF-α in rat serum and BALF. In addition, pre-treatment with both the drugs decreased the levels of MDA and NO_x and increased the levels of GSH in serum. Conclusions Sildenafil and tadalafil decreased…
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