Carvedilol (cas 72956-09-3) attenuates experimentally induced silicosis in rats via modulation of P-AKT/mTOR/TGFβ1 signaling

Add time:07/19/2019    Source:sciencedirect.com

Silicosis is a well acknowledged occupational lung disorder with considerable negative impact on the patients' quality of life. Various signaling pathways have been reported to interplay in the pathogenesis of pulmonary fibro-proliferative disorders; of which, P-AKT/mTOR signaling pathway. The current study highlights the potential pulmonary protective effect of Carvedilol (cas 72956-09-3); a non-selective α/β blocker against experimental silicosis-induced in rats by the intranasal installation of silica (50 mg/rat, 1 ml 0.9% NaCl). Carvedilol (20 mg/kg, orally) was administered for 8 weeks post intranasal silica installation. Carvedilol significantly attenuated silica-induced pulmonary damage on all the investigated scales. Inflammatory, oxidative/anti-oxidative and fibrotic incidences significantly improved with a significant histopathological restoration of lung architecture and attenuation of inflammatory and fibrotic biomarkers expression. Carvedilol significantly reduced lung contents of P-AKT and mTOR which, appears to be the main mechanism underlying the pulmonary protective effect of carvedilol. In conclusion; carvedilol attenuated silica-induced pulmonary fibrosis by modulating P-AKT/mTOR/TGFβ1 signaling and underlying inflammatory and fibrotic sequel.

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