Alterations in oxygen metabolism are associated to lung toxicity triggered by silver nanoparticle exposure.

GARCES M,; MAGNANI NATALIA; CALABRÓ VALERIA; MARCHINI TIMOTEO; CACERES LOURDES; PAMBIANCHI ERIKA; GALDOPORPORA JUAN; VICO TAMARA; SALGUEIRO JIMENA; ZUBILLAGA MARCELA; PECORELLI ALESSANDRA; MORETTON MARCELA; DESIMONE MARTÍN; ALVAREZ, SILVIA; VALACCHI GIUSEPPE; EVELSON PABLO

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2021

0891-5849

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. 99mTc-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 O2 consumption due to increased mitochondrial active respiration and NOX activity. Both O2 consumption processes release ROS triggering the antioxidant system activation as we observed increased SOD and catalase activities and a decreased GSH/GSSG ratio. In A549 cells, exposure to 2.5 μg/mL AgNP during 1 h resulted in an increased NOX activity, decreased mitochondrial ATP associated respiration and higher H2O2 production rate, leading to oxidative damage. Lung 3D tissue model showed AgNP-initiated barrier alterations as TEER values decreased. Taken together, these results show that AgNP exposure alters O2 metabolism leading to a redox imbalance. AgNP-triggered oxidative damage may be responsible for the impaired lung function observed due to alveolar epithelial injury.