Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta, Egypt.
Environ Sci Pollut Res Int. 2021 Apr;28(15):19272-19284. doi: 10.1007/s11356-020-11921-7. Epub 2021 Jan 4.
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.
本研究旨在评估阿司匹林（一种广泛应用的抗炎和心脏保护剂）与磷虾油（一种天然的 omega-3 脂肪酸来源）联合应用对二氧化硅诱导的肺损伤的肺保护和抗纤维化潜力。为了诱导矽肺，将二氧化硅颗粒（50mg/大鼠，0.1mL0.9%NaCl）经鼻腔注入大鼠体内。在暴露于二氧化硅后，每天口服给予阿司匹林（10mg/kg/天）、磷虾油（40mg/kg/天）或两者联合应用 56 天。结果表明，口服阿司匹林和磷虾油联合应用显著减轻了二氧化硅诱导的肺损伤。支气管肺泡灌洗液检查显示乳酸脱氢酶活性、总蛋白含量以及总细胞和分类细胞的积累减少。口服阿司匹林和磷虾油联合应用通过恢复还原型谷胱甘肽浓度和过氧化氢酶活性，以及减轻升高的丙二醛和总一氧化氮含量，显著减轻了二氧化硅诱导的氧化应激。此外，阿司匹林和磷虾油联合应用显示出对二氧化硅诱导的炎症和纤维化介质（核因子 kappa-B、转化生长因子-β1 和基质金属蛋白酶-9）表达的显著抑制作用。通过羟脯氨酸含量的降低和肺组织学结构的明显恢复，也证明了其抗纤维化作用。总之，口服阿司匹林和磷虾油联合应用可对二氧化硅诱导的肺损伤发挥肺保护、抗炎和抗纤维化作用。这种影响可能归因于这种联合应用激活了解决机制，从而抑制了炎症和纤维化生物标志物的表达，并补充了抗氧化剂储存。
