Garcés Mariana, Magnani Natalia D, Pecorelli Alessandra, Calabró Valeria, Marchini Timoteo, Cáceres Lourdes, Pambianchi Erika, Galdoporpora Juan, Vico Tamara, Salgueiro Jimena, Zubillaga Marcela, Moretton Marcela A, Desimone Martin F, Alvarez Silvia, Valacchi Giuseppe, Evelson Pablo
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analítica y Fisicoquímica, Cátedra de Química General e Inorgánica, Argentina; Universidad de Buenos Aires, CONICET, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Facultad de Farmacia y Bioquímica, Argentina.
NC State University, Plants for Human Health Institute, Animal Science Department, USA.
Free Radic Biol Med. 2021 Apr;166:324-336. doi: 10.1016/j.freeradbiomed.2021.02.008. Epub 2021 Feb 14.
Along with the AgNP applications development, the concern about their possible toxicity has increasingly gained attention. As the respiratory system is one of the main exposure routes, the aim of this study was to evaluate the harmful effects developed in the lung after an acute AgNP exposure. In vivo studies using Balb/c mice intranasally instilled with 0.1 mg AgNP/kg b.w, were performed. Tc-AgNP showed the lung as the main organ of deposition, where, in turn, AgNP may exert barrier injury observed by increased protein content and total cell count in BAL samples. In vivo acute exposure showed altered lung tissue O consumption due to increased mitochondrial active respiration and NOX activity. Both O consumption processes release ROS triggering the antioxidant system as observed by the increased SOD, catalase and GPx activities and a decreased GSH/GSSG ratio. In addition, increased protein oxidation was observed after AgNP exposure. In A549 cells, exposure to 2.5 μg/mL AgNP during 1 h resulted in augment NOX activity, decreased mitochondrial ATP associated respiration and higher HO production rate. Lung 3D tissue model showed AgNP-initiated barrier alterations as TEER values decreased and morphological alterations. Taken together, these results show that AgNP exposure alters O metabolism leading to alterations in oxygen metabolism lung toxicity. AgNP-triggered oxidative damage may be responsible for the impaired lung function observed due to alveolar epithelial injury.
随着银纳米颗粒（AgNP）应用的发展，人们对其潜在毒性的关注日益增加。由于呼吸系统是主要的暴露途径之一，本研究旨在评估急性暴露于AgNP后肺部产生的有害影响。使用体重为0.1mg AgNP/kg的Balb/c小鼠进行鼻内滴注的体内研究。锝标记的AgNP（Tc-AgNP）显示肺是主要的沉积器官，反过来，AgNP可能通过支气管肺泡灌洗（BAL）样本中蛋白质含量和细胞总数的增加而造成屏障损伤。体内急性暴露显示，由于线粒体活性呼吸和烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX）活性增加，肺组织氧消耗发生改变。这两种氧消耗过程都会产生活性氧（ROS），从而触发抗氧化系统，表现为超氧化物歧化酶（SOD）、过氧化氢酶（catalase）和谷胱甘肽过氧化物酶（GPx）活性增加以及谷胱甘肽（GSH）/氧化型谷胱甘肽（GSSG）比值降低。此外，AgNP暴露后观察到蛋白质氧化增加。在A549细胞中，暴露于2.5μg/mL AgNP 1小时导致NOX活性增强、线粒体ATP相关呼吸降低以及过氧化氢（HO）产生率升高。肺三维组织模型显示，由于跨上皮电阻（TEER）值降低和形态改变，AgNP引发了屏障改变。综上所述，这些结果表明，AgNP暴露会改变氧代谢，导致肺部氧代谢毒性改变。AgNP引发的氧化损伤可能是由于肺泡上皮损伤导致肺功能受损的原因。
