Acute and Subacute Pulmonary Toxicity Caused by a Single Intratracheal Instillation of Colloidal Silver Nanoparticles in Mice: Pathobiological Changes and Metallothionein Responses

Abstract

To study the acute and subacute pulmonary toxicity of colloidal silver nanoparticles (Ag-NPs), 0 or 100 ppm of Ag-NPs were instilled intratracheally in mice. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF) and histological alterations were determined 1, 3, 7, 15, and 30 days after instillation. Ag-NPs induced moderate pulmonary inflammation and injury on BALF indices during the acute period; however, these changes gradually regressed in a time-dependent manner. Concomitant histopathological and laminin immunohistochemical findings generally correlated to BALF data. Superoxide dismutase and metallothionein expression occurred in particle-laden macrophages and alveolar epithelial cells, which correlated to lung lesions in mice treated with Ag-NPs. These findings suggest that instillation of Ag-NPs causes transient moderate acute lung inflammation and tissue damage. Oxidative stress may underlie the induction of injury to lung tissue. Moreover, the expression of metallothionein in tissues indicated the protective response to exposure to Ag-NPs.

Silver nanoparticles activate endoplasmic reticulum stress signaling pathway in cell and mouse models: The role in toxicity evaluation

“…A recent report showed that AgNP intratracheal instillation could cause acute and subacute pulmonary toxicity in mice at dosage of 1 mg/g body weight [34]. At a lower dosage of 0.5 mg/g body weight, AgNP treatment upregulated the secretion of proinflammatory cytokines and influenced the gene expression profile of lung tissue, but histopathological changes in the lung were only observed at day 1 after instillation [35].…”

“…The lung and the trachea are the direct targets of the damage after acute exposure by intratracheal instillation. Lung inflammation and tissue damage are two main outcomes due to the local high concentrations attained in the lung [34,38]. Two major routes may be involved in the damage in peripheral organs.…”

Use of Synchrotron Radiation-Analytical Techniques To Reveal Chemical Origin of Silver-Nanoparticle Cytotoxicity

“…70 In this case, exposure to AgNPs induced 5-fold increase of mRNA level of MTs at 12 h and 10-fold at 24 h, in accordance with other reports. 61,62,71,72 Binding of silver to MTs was indirectly supported by changes in the secondary structures of MT by circular dichroism (CD) spectra ( Figure 7C and Table 2). Cysteine residues in MTs were bound to I dissolved silver to form AgÀSÀ bonds as indicated by Ag L 3 -edge XANES spectra ( Figure 7D).…”

Lung distribution, quantification, co-localization and speciation of silver nanoparticles after lung exposure in mice

“…It has been shown that expression of MTs is induced in inflammatory lung diseases (Inoue et al, 2008); Kaewamatawong et al (2014) demonstrated the expression of MTs after lung exposure to colloidal Ag ENPs in mice. In a previous study, we showed the inflammatory effects of pulmonary administered Ag ENPs, the same ENPs as used in this study, with infiltration of neutrophils and expression of the pro-inflammatory cytokine IL-1b (Smulders et al, 2014), a known inducer of MT gene expression (De et al, 1990).…”