Anti-fibrotic potential of nicorandil in the treatment of bleomycin induced pulmonary fibrosis

Abstract

Objective: The current study aimed to investigate the possible protective action of Nicorandil in the rat model of Bleomycin induced lung fibrosis. Method: Pulmonary fibrosis was induced by intra-tracheal administration of 0.1 ml of Bleomycin hydrochloride (5 mg/kg in 0.9% NaCl) to wistar albino rats (250-300 g; n=6 per group). Control rats received an equal volume of saline intra-tracheal route. In the treatment groups, the rats were treated with Nicorandil (5 mg/kg per day; subcutaneously) for 28 days. Another group of rats were administered subcutaneously with Sildenafil Citrate (10 mg/kg). Blood was collected from retro-orbital plexus for the assessment of serum Lactate Dehydrogenase (LDH) levels. Broncho-alveolar Lavage fluid (BALF) was collected and evaluated for total and differential cell count. After decapitation, the lungs were excised and taken for microscopic evaluation or stored for the measurement of Glutathione (GSH), Catalase (CAT), Superoxide Dismutase (SOD), Nitric Oxide (NO) and lung parameters like Hydroxyproline content. Results: Nicorandil significantly decreased the Hydroxyproline content, a marker of collagen index, supporting its role in preventing Pulmonary Fibrosis. Also, the levels of total and differential cell count were found to decrease showing prevention of cell damage. The protective role was evident by the reduced levels of LDH and MDA, markers of cell damage as well as increased levels of SOD, CAT, GSH and NO. Conclusion: KATP channel activation may play an important role in the protective effect of nicorandil against bleomycin induced pulmonary fibrosis.