Toxicogenomic Analysis for Livers from Sprague-Daley Rats Following 12-Week Inhalation Exposure to Silver Nanoparticles

Abstract

Silver nanoparticles (AgNPs) have been extensively applied to many industrial and biomedical fields due to their antibacterial effect. However, a large number of applications is also lead to health and environmental safety concerns. Up to date, it was well-known that AgNPs induced reactive oxygen species (ROS) production, cytotoxicity, pro-inflammatory effect, DNA damage, cell cycle disturb, necrosis and apoptosis by many researches. Also, several studies have been performed to investigate the microarray test for AgNPs in many cell types. However, no work reports the AgNPs toxicogenomic study in liver cell line and tissue until now. For this reason, we performed to in vivo toxicogenomic study for AgNPs inhalation exposed liver tissue. After 12 weeks inhalation exposure to AgNPs for the Sprague-Daley rats, we carried out silver concentration measurement for liver tissues and toxicogenomic analysis. As a result, we found that silver concentrations in livers were dose-dependently increased in male and female rats. However, a gender-different accumulation of silver in the livers did not observe. In toxicogenomic study, we observed that 109 and 150 genes significantly up-and down regulated by AgNPs inhalation exposure in male and female rats, respectively. The significantly altered male rat genes were involved in 54 biological pathways which were typically related with diabetes and metabolism. In female rat, the significantly expression changed genes were involved in 89 biological pathways which were mainly connected with metabolism and cell signaling. Plus, the gender-dependent gene expression changes of more than 2 fold were linked to 240 genes, with 114 genes in the male livers and 126 genes in the female livers. These were related to steroids and xenobiotics metabolism pathway.

The role of sex in particle‐induced inflammation and injury

“…A similar trend was found in another study investigating the relationship between T2D and insulin resistance and exposure to vehicle emissions (Table 7); a significant relationship between exposure and T2D prevalence was only found in women (Brook et al, 2008). PM 2.5 toxicity may overlap mechanistically with Ag NPs where upregulation of genes related to diabetes has been observed in the livers of rats (Kim et al, 2016;Table 2). However, rodent studies only revealed an association of Ag Np inhalation and T2D in male animals, as opposed to the results of human PM 2.5 studies, which suggest that women are more susceptible than men.…”

“…No sex-differences in hepatic Ag NP accumulation was observed. Both male and female rats had increased metabolism-related gene expression in the liver, but only males upregulated genes involved with xenobiotic metabolism in the kidneys (Kim et al, 2016), which may explain differences in renal clearance and accumulation observed in other studies. In contrast to accumulation data, Sung et al (2009) showed that Ag NP-treated male animals had a greater decrease in kidney function, as indicated by tubular basophilia and urine protein, compared to females.…”

“…This study also analyzed changes in kidney gene expression and reported that females had an increase in extracellular signaling genes related to ECM receptor interaction, MAPK, and PPAR signaling pathways (Dong et al, 2013). In another study, there was a similar increase in hepatic gene expression of female rats, but in the livers of male rats, there was increased expression of diabetes-related genes (Kim et al, 2016). No sex-differences in hepatic Ag NP accumulation was observed.…”