Krill oil and low-dose aspirin combination mitigates experimentally induced silicosis in rats: role of NF-κB/TGF-β1/MMP-9 pathway.

Abstract

This study is an attempt to assess pulmonary protective and antifibrotic potentials of a combination of aspirin, a widely used anti-inflammatory and cardioprotective agent, and krill oil, a naturally occurring omega-3 fatty acid source, against silica-induced pulmonary injury. For silicosis induction, silica particles (50 mg/rat, 0.1 mL 0.9% NaCl) were instilled intranasally into rats. Aspirin (10 mg/kg/day), krill oil (40 mg/kg/day), or their combination was administered orally for 56 days following silica exposure. Results showed that oral aspirin and krill oil combination significantly mitigated silica-induced pulmonary injury. Bronchoalveolar lavage fluid examination showed a decreased lactate dehydrogenase activity, total protein content, and accumulation of total and differential inflammatory cells. Oral aspirin and krill oil combination significantly attenuated silica-induced oxidative stress through the restoration of reduced glutathione concentration and catalase activity in addition to alleviation of elevated malondialdehyde and total nitric oxide contents. Moreover, aspirin and krill oil combination revealed considerable mitigation of silica-induced upregulated expression of the inflammatory and fibrotic mediators: nuclear factor kappa-B, transforming growth factor-β1, and matrix metalloproteinase-9. The antifibrotic effect was also evidenced through the decreased hydroxyproline content and the obvious restoration of lung architecture, as demonstrated upon histopathological examination. In conclusion, oral aspirin and krill oil combination can confer pulmonary protective, anti-inflammatory, and antifibrotic potentials against silica-induced pulmonary injury. This impact could be credited to the ability of this combination to activate resolution mechanisms, which, in turn, suppress the expression of inflammatory and fibrotic biomarkers and replenish antioxidant stores.