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

MARIANA, GARCÉS; NATALIA D, MAGNANI; ALESSANDRA, PECORELLI; VALERIA, CALABRÓ; TIMOTEO, MARCHINI; LOURDES, CÁCERES; ERIKA, PAMBIANCHI; JUAN, GALDOPORPORA; TAMARA, VICO; JIMENA, SALGUEIRO; MARCELA, ZUBILLAGA; MARCELA A, MORETTON; MARTIN F, DESIMONE; SILVIA, ALVAREZ; GIUSEPPE, VALACCHI; PABLO, EVELSON

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Año: 2021 vol. 166 p. 324 - 336

0891-5849

Along with the AgNP applications development, the concern about their possibletoxicity has increasingly gained attention. As the respiratory system is one of the mainexposure routes, the aim of this study was to evaluate the harmful effects developed inthe lung after an acute AgNP exposure. In vivo studies using Balb/c mice intranasallyinstilled with 0.1 mg AgNP/kg b.w, were performed. 99mTc-AgNP showed the lung asthe main organ of deposition, where, in turn, AgNP may exert barrier injury observedby increased protein content and total cell count in BAL samples. In vivo acute exposureshowed altered lung tissue O2 consumption due to increased mitochondrial activerespiration and NOX activity. Both O2 consumption processes release ROS triggeringthe antioxidant system as observed by the increased SOD, catalase and GPx activitiesand a decreased GSH/GSSG ratio. In addition, increased protein oxidation was observedafter AgNP exposure. In A549 cells, exposure to 2.5 μg/mL AgNP during 1 h resultedin augment NOX activity, decreased mitochondrial ATP associated respiration andhigher H2O2 production rate. Lung 3D tissue model showed AgNP-initiated barrieralterations as TEER values decreased and morphological alterations. Taken together,these results show that AgNP exposure alters O2 metabolism leading to alterations inoxygen metabolism lung toxicity. AgNP-triggered oxidative damage may beresponsible for the impaired lung function observed due to alveolar epithelial injury.