School of Medicine, University of Zagreb, Šalata 3, 10 000, Zagreb, Croatia.
Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000, Zagreb, Croatia.
Part Fibre Toxicol. 2021 Oct 18;18(1):38. doi: 10.1186/s12989-021-00425-y.
Silver nanoparticles (AgNPs) are widely used in biomedicine due to their strong antimicrobial, antifungal, and antiviral activities. Concerns about their possible negative impacts on human and environmental health directed many researchers towards the assessment of the safety and toxicity of AgNPs in both in vitro and in vivo settings. A growing body of scientific information confirms that the biodistribution of AgNPs and their toxic effects vary depending on the particle size, coating, and dose as well as on the route of administration and duration of exposure. This study aimed to clarify the sex-related differences in the outcomes of oral 28 days repeated dose exposure to AgNPs.
Wistar rats of both sexes were gavaged daily using low doses (0.1 and 1 mg Ag/kg b.w.) of polyvinylpyrrolidone (PVP)-coated small-sized (10 nm) AgNPs. After exposure, blood and organs of all rats were analysed through biodistribution and accumulation of Ag, whereas the state of the liver and kidneys was evaluated by the levels of reactive oxygen species (ROS) and glutathione (GSH), catalase (CAT) activity, superoxide dismutase (SOD) and glutathione peroxidase (GPx), expression of metallothionein (Mt) genes and levels of Mt proteins.
In all animals, changes in oxidative stress markers and blood parameters were observed indicating the toxicity of AgNPs applied orally even at low doses. Sex-related differences were noticed in all assessed parameters. While female rats eliminated AgNPs from the liver and kidneys more efficiently than males when treated with low doses, the opposite was observed for animals treated with higher doses of AgNPs. Female Wistar rats exposed to 1 mg PVP-coated AgNPs/kg b.w. accumulated two to three times more silver in the blood, liver, kidney and hearth than males, while the accumulation in most organs of digestive tract was more than ten times higher compared to males. Oxidative stress responses in the organs of males, except the liver of males treated with high doses, were less intense than in the organs of females. However, both Mt genes and Mt protein expression were significantly reduced after treatment in the liver and kidneys of males, while they remained unchanged in females.
Observed toxicity effects of AgNPs in Wistar rats revealed sex-related differences in response to an oral 28 days repeated exposure.
由于银纳米粒子（AgNPs）具有很强的抗菌、抗真菌和抗病毒活性，因此在生物医药领域得到了广泛应用。由于担心它们可能对人类和环境健康造成负面影响，许多研究人员开始评估 AgNPs 在体外和体内环境中的安全性和毒性。越来越多的科学信息证实，AgNPs 的生物分布及其毒性作用因颗粒大小、涂层、剂量以及给药途径和暴露时间的不同而有所不同。本研究旨在阐明口服 28 天重复剂量暴露于 AgNPs 后，雄性和雌性大鼠的结果存在性别差异。
使用低剂量（0.1 和 1mg Ag/kg bw）的聚乙烯吡咯烷酮（PVP）包覆的小尺寸（10nm）AgNPs 通过灌胃的方式每天对雄性和雌性 Wistar 大鼠进行处理。暴露后，通过 Ag 的生物分布和积累分析所有大鼠的血液和器官，通过活性氧（ROS）和谷胱甘肽（GSH）的水平、过氧化氢酶（CAT）活性、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）、金属硫蛋白（Mt）基因的表达和 Mt 蛋白的水平来评估肝脏和肾脏的状态。
所有动物的氧化应激标志物和血液参数均发生变化，表明即使在低剂量下，口服 AgNPs 也具有毒性。所有评估的参数都存在性别差异。当用低剂量处理时，雌性大鼠比雄性大鼠更有效地从肝脏和肾脏中排出 AgNPs，但当用更高剂量的 AgNPs 处理时则相反。暴露于 1mg PVP 包覆的 AgNPs/kg bw 的雌性 Wistar 大鼠血液、肝脏、肾脏和心脏中的银积累量比雄性大鼠高 2 到 3 倍，而在大多数消化器官中的积累量比雄性大鼠高 10 倍以上。除了高剂量处理的雄性大鼠的肝脏外，雄性大鼠的器官中的氧化应激反应不如雌性大鼠强烈。然而，无论是在肝脏还是肾脏，雄性大鼠的 Mt 基因和 Mt 蛋白表达在治疗后都显著降低，而在雌性大鼠中则保持不变。
在 Wistar 大鼠中观察到的 AgNPs 的毒性作用表明，口服 28 天重复暴露会导致对雄性和雌性大鼠的反应存在性别差异。
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