Gene Expression Changes in Rat Liver and Testes after Lung Instillation of a Low Dose of Silver Nanoparticles

The expression profile of genes involved in oxidative stress, metal toxicity, apoptosis/cell cycle, and protein folding was investigated in liver and testis of Sprague-Dawley rats at different time intervals after i.t. instillation of AgNP (20 nm, 50 μg/rat). At 7 days, selective changes in the expression of genes encoding oxidative stress-related enzymes, namely Gpx1, SOD, FMO2 and GAPDH were observed in hepatic and testicular tissues. Other genes implicated in oxidative stress (Txnrd1, Gss, Gsr), metal toxicity (Mt1), apoptosis/cell cycle (casp3, p53), and protein-folding processes (Hsp70) were not modified. Gene expression was modulated by AgNPs in a tissueand time-dependent manner. In particular, SOD was up-regulated in both tissues, but significant Gpx1, FMO2, and GAPDH overexpression was seen in testes only. No gene expression changes were seen in both tissues 28 days post-instillation. Unlike AgNPs, pulmonary treatment with AgNO3 (7 μg/rat), did not cause gene expression changes in both tissues at both time points studied, suggesting that dissimilar mechanisms are implicated in toxicity and/or biokinetics of nanoparticulate and ionic silver. The results demonstrate subtle systemic changes involving selected oxidative stress-related genes in the liver and testis of animals exposed by pulmonary route to a low dose of AgNPs. These effects were apparently reversible as changes were observed at day 7 but not day 28. Recovery could possibly reflect either compensatory mechanism contrasting the initial toxicogenomic response to AgNPs or the silver removal from the tested organs. These findings may be of toxicological relevance in relation to possible health risks associated with occupational or consumer exposure to nanosilver. resulting from the distribution of silver from the lung to multiple secondary organs. For example, a subchronic 90-day inhalation study in rats exposed to 18 nm AgNPs (49 to 515 μg/m3) revealed dosedependent hepatic alterations with bile-duct hyperplasia, singlecell hepatocellular necrosis with increased cellular eosinophilia and shrunken condensed nuclei in the animals treated with the highest AgNP dose [13]. Hepatic inflammatory changes were also described in mice treated with AgNPs by oral route [14] or injection [15]. Biokinetic studies in animals given AgNPs by inhalation or lung instillation have shown distribution of silver to multiple organs, with increased silver levels in liver and testis [12,16-23]. Transfer of silver across the blood-testis barrier and predominant localization of silver in liver and testis of laboratory animals was also reported after administration of AgNPs by oral route [24] or injection [15,25]. Excessive testicular levels of silver were still measurable in the animals examined 8 weeks after treatment suggesting incomplete tissue elimination and some retention of the metal after exposure to AgNPs [24]. Crossing of blood-testis barrier by intravenously administered AgNPs has also been shown in rabbits at doses which did not affect the general health status of the animal, libido, serum testosterone, semen Citation: Coccini T, Gornati R, Rossi F, Signoretto E, Vanetti I, et al. (2014) Gene Expression Changes in Rat Liver and Testes after Lung Instillation of a Low Dose of Silver Nanoparticles. J Nanomed Nanotechnol 5: 227. doi: 10.4172/2157-7439.1000227