Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NM)

Abstract

Several reports on amorphous silica nanomaterial (aSiO2 NM) toxicity have been questioning their safety. Herein, we investigated the in vivo pulmonary toxicity of four variants of aSiO2 NM: SiO2_15_Unmod, SiO2_15_Amino, SiO2_7 and SiO2_40. We focused on alterations in lung DNA and protein integrity, and gene expression following single intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO2_7, using TiO2_NM105 as a benchmark NM. In the instillation study, a significant but slight increase in oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO2_15_Amino was observed in the recovery (R) group. Exposure to SiO2_7 or SiO2_40 markedly increased oxidative DNA lesions in rat lung cells of the exposure (E) group at every tested dose. This damage seems to be repaired, since no changes compared to controls were observed in the R groups. In STIS, a significant increase in DNA strand breaks of the lung cells exposed to 0.5 mg/m3 of SiO2_7 or 50 mg/m3 of TiO2_NM105 was observed in both groups. The detected gene expression changes suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage. Overall, all tested aSiO2 NM were not associated with marked in vivo toxicity following instillation or STIS. The genotoxicity findings for SiO2_7 from instillation and STIS are concordant; however, changes in STIS animals were more permanent/difficult to revert.

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

“…Some in vivo and in vitro studies have shown that SiO 2 NPs can cause toxicity to different organs in the human body; toxicity has been demonstrated in lung epithelial cells [ 9 ], liver cells [ 10 ], intestinal cells [ 11 ], the lungs [ 12 ], and kidneys [ 13 ]. In addition, SiO 2 NPs were found to induce genotoxicity and alterations in gene and protein expression [ 12 , 14 ], and Chen et al [ 15 ] reported that SiO 2 NPs can induce cornea toxicity.…”

“…Some in vivo and in vitro studies have shown that SiO 2 NPs can cause toxicity to different organs in the human body; toxicity has been demonstrated in lung epithelial cells [ 9 ], liver cells [ 10 ], intestinal cells [ 11 ], the lungs [ 12 ], and kidneys [ 13 ]. In addition, SiO 2 NPs were found to induce genotoxicity and alterations in gene and protein expression [ 12 , 14 ], and Chen et al [ 15 ] reported that SiO 2 NPs can induce cornea toxicity. The local ocular delivery of medicine has become an important strategy for treating retinal diseases [ 16 – 18 ], and intravitreal injection has become a common treatment method for various retinal diseases including diabetic retinopathy, macular degeneration, macular edema, and inflammatory diseases [ 19 , 20 ].…”

“…Tassinari et al [ 27 ] that amorphous SiO 2 NPs induced acute toxicity in the liver and spleen of male and female rats after intravenous administration. Brandão et al [ 12 ] demonstrated that amorphous SiO 2 NPs induced genotoxicity in lung cells. Particle size is also an important factor affecting the toxicity of SiO 2 NPs.…”