Assessment of genotoxicity and biodistribution of nano‐ and micron‐sized yttrium oxide in rats after acute oral treatment

Abstract

The increasing use of yttrium oxide (Y O ) nanoparticles (NPs) entails an improved understanding of their potential impact on the environmental and human health. In the present study, the acute oral toxicity of Y O NPs and their microparticles (MPs) was carried out in female albino Wistar rats with 250, 500 and 1000 mg kg body weight doses. Before the genotoxicity evaluation, characterization of the particles by transmission electron microscopy, dynamic light scattering and laser Doppler velocimetry was performed. The genotoxicity studies were conducted using micronucleus and comet assays. Results showed that Y O NP-induced significant DNA damage at higher dose (1000 mg kg body weight) in peripheral blood leukocytes and liver cells, micronucleus formation in bone marrow and peripheral blood cells. The findings from biochemical assays depicted significant alterations in aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase and lactate dehydrogenase levels in serum, liver and kidneys at the higher dose only. Furthermore, tissue biodistribution of both particles was analyzed by inductively coupled plasma optical emission spectrometry. Bioaccumulation of yttrium (Y) in all tissues was significant and dose-, time- and organ-dependent. Moreover, Y O NP-treated rats exhibited higher tissue distribution along with greater clearance through urine whereas Y O MP-dosed animals depicted the maximum amount of Y in the feces. Hence, the results indicated that bioaccumulation of Y O NPs via its Y ions may induce genotoxic effects.

A systematic quality evaluation and review of nanomaterial genotoxicity studies: a regulatory perspective

“…These studies included a single oral exposure with female Wistar rats, and a 28-day repeated oral exposure study with both male and female Wistar rats. Comet and MN assays for liver and peripheral blood erythrocytes, respectively, were all positive in rats treated with a single dose of Y 2 O 3 , and both single and repeated dose of WO 3 at the highest tested dose (1000 mg/kg body weight) [ 68 – 70 ]. In rats treated with a repeated dose of Y 2 O 3 , all tests were positive already at 120–480 mg/kg body weight [ 71 ].…”

Assessment of genotoxicity and biodistribution of nano‐ and micron‐sized yttrium oxide in rats after acute oral treatment

“…When this paper (Panyala et al, 2017) was first published, there was a problem with Figure 2. The caption stated that Figure 2G,I showed the normal architecture of the heart and spleen and that Figure 2H,J showed that there was no pathological alterations in the heart and spleen of the Y2 O3 NO‐treated group.…”

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

“…Following ingestion, translocation of particles into and across the GIT mucosa can occur via four mechanisms: 1) endocytosis, through enterocytes, 2) the M-cell-rich layer of Peyer's patches (small-intestine lymphoid aggregates), 3) persorption, where particles can translocate through a "hole" left in the epithelium when enterocytes shed from the villous tip, and 4) the paracellular route, where NPs pass through weakened tight junctions of the epithelial cell layer. [17][18][19][20] Moreover, NP translocation and interactions with tissues in the GIT can be influenced by size, morphology, hydrophilic-hydrophobic balance, and surface functionalization of the particles in question. For example, it has been suggested that negatively charged materials exhibit poor bioavailability, due to electrostatic repulsion and mucus entrapment.…”