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急性经口给予大鼠后纳米和微米级氧化钇的遗传毒性和生物分布评估。

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

机构信息

Toxicology Unit, Pharmacology and Toxicology Division, CSIR - Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India.

Academy of Scientific and Innovative Research, CSIR - Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India.

出版信息

J Appl Toxicol. 2017 Dec;37(12):1379-1395. doi: 10.1002/jat.3505. Epub 2017 Jul 7.

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.

摘要

氧化钇(Y 2 O 3 )纳米颗粒(NPs)的使用日益增多,因此需要更好地了解其对环境和人类健康的潜在影响。本研究采用雌性白化 Wistar 大鼠,以 250、500 和 1000 mg/kg 体重的剂量,进行了 Y 2 O 3 NPs 和其微颗粒(MPs)的急性经口毒性试验。在进行遗传毒性评估之前,通过透射电子显微镜、动态光散射和激光多普勒测速对颗粒进行了表征。遗传毒性研究采用微核和彗星试验进行。结果表明,Y 2 O 3 NP 在较高剂量(1000 mg/kg 体重)下可诱导外周血白细胞和肝细胞的 DNA 显著损伤,骨髓和外周血细胞中的微核形成。生化分析结果显示,在较高剂量下,血清、肝脏和肾脏中的天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、丙二醛、超氧化物歧化酶、还原型谷胱甘肽、过氧化氢酶和乳酸脱氢酶水平均发生显著变化。此外,还通过电感耦合等离子体发射光谱法分析了两种颗粒在体内的组织分布。两种颗粒的钇(Y)在所有组织中的生物累积均显著,且与剂量、时间和器官有关。此外,Y 2 O 3 NP 处理的大鼠表现出更高的组织分布和通过尿液的更快清除,而 Y 2 O 3 MP 处理的动物在粪便中显示出最大量的 Y。因此,结果表明,Y 2 O 3 NPs 通过其 Y 离子的生物累积可能会引起遗传毒性。

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