Silver Nanoparticle Exposure Causes Pulmonary Structural Damage and Mitochondrial Dynamic Imbalance in the Rat: Protective Effects of Sodium Selenite

Abstract

Wanrui Ma, 1–3 Shan He, 4 Huiyan Ma, 4 Haifeng Jiang, 5 Ning Yan, 6 Lili Zhu, 6 John J Bang, 3 P Andy Li, 2 Shaobin Jia 6 1Department of General Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, Durham, NC, USA; 3Department of Environmental, Earth and Geospatial Sciences, North Carolina Central University, Durham, NC, USA; 4School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of hina; 5Department of Pathology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 6Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of ChinaCorrespondence: P Andy LiDepartment of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, 1801 Fayetteville Street, Durham, NC 27707, USATel [phone]Fax [phone]Email [email protected] JiaHeart Centre, General Hospital of Ningxia Medical University, 804 Shengli South Street, Xingqing District, Yinchuan 750004, People’s Republic of ChinaTel [phone]Email [email protected]: With the increased application of Silver nanoparticles (AgNP), its potential concerns to the health of human beings remain to be defined. This study aims to explore the harmful effects of AgNP on lung tissue in animals and to examine the mechanisms of protection achieved by sodium selenite.Methods: Sprague-Dawley(SD) rats were exposed to AgNP (200 μL,1mg/mL) through a single intratracheal instillation. Sodium selenite (0.2mg/kg) was i.p. injected. Malondialdehyde (MDA) and glutathione (GSH) were measured using a spectrophotometer. Histological outcomes and ultrastructural changes were assessed by hematoxylin and eosin (HE) staining and electronic microscopy. Caspases and mitochondrial fission and fusion markers were measured by Western blotting.Results: The histopathologic findings showed that AgNP significantly increased the thickness of alveolar septa, accumulation of macrophage, and the formation of pulmonary bullae and pulmonary consolidation. Ultrastructural studies showed localization of AgNP inside the mitochondria, hyperplasia and vacuolation of type I and type II alveolar cells, lysis of osmiophilic lamellar bodies, and swollen of the mitochondria. AgNP elevated MDA and reduced GSH levels. AgNP activated caspases-3, increased mitochondrial fission markers Dynamin-related protein 1 (Drp1) and phospho-Drp1(p-Drp1), and decreased fusion proteins optic atrophy 1 (Opa1) and mitofusins 2 (Mfn2). Treatment with sodium selenite for 7 days corrected the AgNP-caused alterations in morphological, ultrastructural, oxidative stress, caspase-3 activation and mitochondrial dynamic imbalance.Conclusion: We conclude that the exposure of AgNP causes lung tissue damage by enhances oxidative stress, activates caspases-3, and triggers mitochondrial dynamic imbalance towards fission. Sodium selenite effectively detoxifies the AgNP-induced damage to the lung tissue by preventing the above alterations.Keywords: silver nanoparticle, selenium, pulmonary, mitochondrial dynamics, mitochondrial morphology

Keywords

• silver nanoparticle
• selenium
• pulmonary
• mitochondrial dynamics
• mitochondrial morphology