Beijing Institute of Medical Device Testing, Beijing Center for Testing and Research of Medical Biological Protective Equipment, Beijing 101111, China.
Beijing Institute of Technology, School of Life Science, Beijing 100081, China.
Molecules. 2023 Jul 30;28(15):5757. doi: 10.3390/molecules28155757.
Nickel nanoparticles (NiNPs) have wide applications in industry and biomedicine due to their unique characteristics. The liver is the major organ responsible for nutrient metabolism, exogenous substance detoxification and biotransformation of medicines containing nanoparticles. Hence, it is urgent to further understand the principles and potential mechanisms of hepatic effects on NiNPs administration. In this study, we explored the liver impacts in male C57/BL6 mice through intraperitoneal injection with NiNPs at doses of 10, 20 and 40 mg/kg/day for 7 and 28 days. The results showed that NiNPs treatment increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and induced pathological changes in liver tissues. Moreover, hepatic triglyceride (TG) content and lipid droplet deposition identified via lipogenesis (DNL) progression were enhanced after NiNPs injection. Additionally, sustained NiNPs exposure induced a remarkable hepatic inflammatory response, significantly promoted endoplasmic reticulum stress (ER stress) sensors Ire1α, Perk and Atf6, and activated the occurrence of liver cell apoptosis. Overall, the research indicated that NiNPs exposure induced liver injury and disturbance of lipid metabolism. These findings revealed the public hazard from extreme exposure to NiNPs and provided new information on biological toxicity and biosafety evaluation.
镍纳米颗粒（NiNPs）由于其独特的特性，在工业和生物医学中有广泛的应用。肝脏是负责营养代谢、外源物质解毒和含纳米颗粒药物生物转化的主要器官。因此，迫切需要进一步了解肝脏对 NiNPs 给药的作用原理和潜在机制。在这项研究中，我们通过腹腔注射不同剂量（10、20 和 40mg/kg/天）的 NiNPs 来研究雄性 C57/BL6 小鼠的肝脏影响，持续 7 天和 28 天。结果表明，NiNPs 处理会增加血清中丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的水平，并导致肝脏组织发生病理变化。此外，通过脂肪生成（DNL）的进展，肝组织甘油三酯（TG）含量和脂质滴沉积增加。此外，持续的 NiNPs 暴露会引起明显的肝炎症反应，显著促进内质网应激（ER stress）传感器 Ire1α、Perk 和 Atf6 的激活，并促进肝细胞凋亡的发生。总的来说，该研究表明 NiNPs 暴露会导致肝损伤和脂质代谢紊乱。这些发现揭示了极端暴露于 NiNPs 所带来的公共危害，并为生物毒性和生物安全性评估提供了新的信息。
