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重复给予 Wistar 大鼠氧化镍纳米颗粒的口服毒性研究:组织病理学和生物化学角度。

Repeated oral dose toxicity study of nickel oxide nanoparticles in Wistar rats: a histological and biochemical perspective.

机构信息

Toxicology Lab, Applied Biology Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

出版信息

J Appl Toxicol. 2019 Jul;39(7):1012-1029. doi: 10.1002/jat.3790. Epub 2019 Mar 6.

DOI:10.1002/jat.3790
PMID:30843265
Abstract

Despite the increasing use of nickel oxide (NiO) nanoparticles (NPs), limited information is available on their toxicological effects. Health consequences of 28 days repeated oral exposure to NiO NPs have not been explored thoroughly. Hence, toxicity investigations were performed after 28-day daily exposure in albino Wistar rats with NiO NPs following Organization for Economic Co-operation and Development test guideline 407. Histopathology, biochemical indices including oxidative stress and biodistribution patterns were evaluated to decipher the toxicological impact of NiO NPs. NiO NP characterization by transmission electron microscopy showed an average size of 12.9 (±3.4) nm. Histological studies depicted a prominent impact on the vital organs of the rats. A dose-dependent rise in both aminotransferase enzyme values was recorded in the homogenates of liver and kidney tissues. A significant decrease in superoxide dismutase activity and increase in catalase activity was noted. Further, a dose-dependent decrease in reduced glutathione content was recorded in rats, which suggested generation of reactive oxygen species and oxidative stress. Increase in the malondialdehyde levels was observed with an increase in the dose substantiating the antioxidant enzyme activity profiles. Biodistribution studies indicated maximum accumulation of Ni content in liver followed by kidney. Excretion of Ni was predominantly through feces and a little through renal clearance. Our study indicated that NiO NPs adversely alter the biochemical profile of the rats and cause histological damage. Further investigations are warranted to address the mechanism by which physiological path these NiO NPs exhibit their toxic nature in in vivo.

摘要

尽管氧化镍 (NiO) 纳米颗粒 (NPs) 的使用越来越多,但关于其毒理学效应的信息有限。NiO NPs 重复口服 28 天的健康后果尚未得到充分探索。因此,根据经济合作与发展组织测试指南 407,在白化 Wistar 大鼠中进行了 28 天每日暴露后,进行了毒性研究。评估了组织病理学、生化指标(包括氧化应激和生物分布模式),以阐明 NiO NPs 的毒理学影响。透射电子显微镜对 NiO NP 的表征显示平均粒径为 12.9(±3.4)nm。组织学研究表明 NiO NPs 对大鼠的重要器官有明显影响。在肝和肾组织匀浆中,两种氨基转移酶值均呈剂量依赖性升高。超氧化物歧化酶活性显著降低,过氧化氢酶活性增加。此外,大鼠的还原型谷胱甘肽含量呈剂量依赖性下降,表明活性氧和氧化应激的产生。随着剂量的增加,丙二醛水平增加,证实了抗氧化酶活性谱。生物分布研究表明,Ni 含量在肝脏中的积累最大,其次是肾脏。Ni 的排泄主要通过粪便,少量通过肾脏清除。我们的研究表明,NiO NPs 会改变大鼠的生化特征并引起组织学损伤。需要进一步研究以阐明 NiO NPs 在体内表现出其毒性的生理途径的机制。

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