Nicorandil ameliorates pulmonary inflammation and fibrosis in a rat model of silicosis

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Abstract

Nicorandil, an antianginal and potassium channel opener agent, has different useful impacts on cardiovascular and respiratory systems. Its effect against silicosis has not been discussed yet, therefore, this is an attempt to decide whether nicorandil can reduce silica-induced lung injury in rats. Silica model was induced by intranasal instillation of silica dust once. Rats were given nicorandil for 56 days after exposure to silica. Results showed that nicorandil significantly alleviated silica-induced inflammation as it decreased the elevated levels of total and differential cell counts, pulmonary edema (revealed by decreased lung/body weight ratio and W/D weight ratio), LDH and total protein levels in BALF. Notably, nicorandil decreased collagen deposition as evidenced by reduction in levels of hydroxyproline and collagen in lung tissues as well as obvious alleviation in silica-induced fibrosis in histopathological findings. Nicorandil effectively reduced the increased expression of NF-κB and iNOS and decreased MPO levels in lung tissues. Moreover, nicorandil abolished oxidative and nitrosative stress via reducing levels of pulmonary MDA and NOx concomitant with elevating levels of pulmonary GSH and SOD. Meanwhile, nicorandil decreased the levels of TNF-α and TGF-β, up regulated Nrf-2 and HO-1 levels in BALF suggesting antioxidant, anti-inflammatory and antifibrotic properties. In summary, nicorandil can confer protection against silica-induced lung inflammation and fibrosis. This impact might be due to its ability to down regulate the production of inflammatory and fibrotic cytokines in addition to restoring oxidant/antioxidant balance.

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