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3.
Mutagenesis ; 34(2): 181-201, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-30753658

RESUMO

Despite their enormous advantages, nanoparticles (NPs) have elicited disquiet over their safety. Among the numerous NPs, yttrium oxide (Y2O3) NPs are utilised in many applications. However, knowledge about their toxicity is limited, and it is imperative to investigate their potential adverse effects. Therefore, this study explored the effect of 28 days of repeated oral exposure of Wistar rats to 30, 120 and 480 mg/kg body weight (bw) per day of Y2O3 NPs and microparticles (MPs). Before initiation of the study, characterisation of the particles by transmission electron microscopy, dynamic light scattering, Brunauer-Emmett-Teller and laser Doppler velocimetry was undertaken. Genotoxicity was evaluated using the comet and micronucleus (MN) assays. Biochemical markers aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase and lactate dehydrogenase in serum, liver and kidney were determined. Bioaccumulation of the particles was analysed by inductively coupled plasma optical emission spectrometry. The results of the comet and MN assays showed significant differences between the control and groups treated with 120 and 480 mg/kg bw/day Y2O3 NPs. Significant biochemical alterations were also observed at 120 and 480 mg/kg bw/day. Haematological and histopathological changes were documented. Yttrium (Y) biodistribution was detected in liver, kidney, blood, intestine, lungs, spleen, heart and brain in a dose- and the organ-dependent manner in both the particles. Further, the highest levels of Y were found in the liver and the lowest in the brain of the treated rats. More of the Y from NPs was excreted in the urine than in the faeces. Furthermore, NP-treated rats exhibited much higher absorption and tissue accumulation. These interpretations furnish rudimentary data of the apparent genotoxicity of NPs and MPs of Y2O3 as well as the biodistribution of Y. A no-observed adverse effect level of 30 mg/kg bw/day was found after oral exposure of rats to Y2O3 NPs.


Assuntos
Dano ao DNA , Nanopartículas Metálicas/toxicidade , Ítrio/toxicidade , Administração Oral , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Feminino , Intestino Delgado/citologia , Intestino Delgado/efeitos dos fármacos , Rim/citologia , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/metabolismo , Leucócitos/citologia , Leucócitos/enzimologia , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Ratos , Ratos Wistar , Baço/citologia , Baço/efeitos dos fármacos , Distribuição Tecidual , Ítrio/administração & dosagem
4.
J Appl Toxicol ; 38(6): 896-913, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29405315

RESUMO

The exigency of semiconductor and super capacitor tungsten oxide nanoparticles (WO3 NPs) is increasing in various sectors. However, limited information on their toxicity and biological interactions are available. Hence, we explored the underlying mechanisms of toxicity induced by WO3 NPs and their microparticles (MPs) using different concentrations (0-300 µg ml-1 ) in human lung carcinoma (A549) cells. The mean size of WO3 NPs and MPs by transmission electron microscopy was 53.84 nm and 3.88 µm, respectively. WO3 NPs induced reduction in cell viability, membrane damage and the degree of induction was size- and dose-dependent. There was a significant increase in the percentage tail DNA and micronuclei formation at 200 and 300 µg ml-1 after 24 hours of exposure. The DNA damage induced by WO3 NPs could be attributed to increased oxidative stress and inflammation through reactive oxygen species generation, which correlated with the depletion of reduced glutathione content, catalase and an increase in malondialdehyde levels. Cellular uptake studies unveiled that both the particles were attached/surrounded to the cell membrane according to their size. In addition, NP inhibited the progression of the cell cycle in the G2 /M phase. Other studies such as caspase-9 and -3 and Annexin-V-fluorescein isothiocyanate revealed that NPs induced intrinsic apoptotic cell death at 200 and 300 µg ml-1 concentrations. However, in comparison to NPs, WO3 MPs did not incite any toxic effects at the tested concentrations. Under these experimental conditions, the no-observed-significant-effect level of WO3 NPs was determined to be ≤200 µg ml-1 in A549 cells.


Assuntos
Adenocarcinoma Bronquioloalveolar/patologia , Dano ao DNA , Neoplasias Pulmonares/patologia , Nanopartículas Metálicas/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Óxidos/toxicidade , Tungstênio/toxicidade , Células A549 , Adenocarcinoma Bronquioloalveolar/genética , Adenocarcinoma Bronquioloalveolar/metabolismo , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/patologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Nível de Efeito Adverso não Observado , Estresse Oxidativo/efeitos dos fármacos , Óxidos/metabolismo , Tamanho da Partícula , Fatores de Tempo , Tungstênio/metabolismo
5.
J Appl Toxicol ; 37(12): 1379-1395, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28685832

RESUMO

The increasing use of yttrium oxide (Y2 O3 ) 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 Y2 O3 NPs and their microparticles (MPs) was carried out in female albino Wistar rats with 250, 500 and 1000 mg kg-1 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 Y2 O3 NP-induced significant DNA damage at higher dose (1000 mg kg-1 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, Y2 O3 NP-treated rats exhibited higher tissue distribution along with greater clearance through urine whereas Y2 O3 MP-dosed animals depicted the maximum amount of Y in the feces. Hence, the results indicated that bioaccumulation of Y2 O3 NPs via its Y ions may induce genotoxic effects.


Assuntos
Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Mutagênicos/toxicidade , Nanopartículas/toxicidade , Ítrio/toxicidade , Administração Oral , Animais , Ensaio Cometa , Feminino , Testes para Micronúcleos , Mutagênicos/farmacocinética , Especificidade de Órgãos , Tamanho da Partícula , Ratos Wistar , Distribuição Tecidual , Ítrio/farmacocinética
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