Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
J Biochem Mol Toxicol. 2019 Jul;33(7):e22324. doi: 10.1002/jbt.22324. Epub 2019 Apr 5.
Due to their unique properties including cellular uptake and the delivery efficiency to biological systems, nanoparticles are used in various preclinical and clinical applications. The aim of this study was to investigate the toxicity impacts of zinc oxide nanoparticles (ZnO-NPs) on morphology and functionality of the rat's liver and spleen and illustrated its safe-therapeutic doses.
The 28 female Swiss albino rats (180-220 g) and two human hepatocyte cell lines (HepG2 and HUH7) were designed as an in vivo and in vitro study, respectively. Samples were treated with certain doses of ZnO-NPs. The rat's liver morphology and functionality and apoptotic genes expression profile (Bax, Bcl-2, and P53) were analyzed to detect the cytotoxicity and antitumor impacts of ZnO-NPs, respectively.
The results showed a positive significant association between the increasing doses of ZnO-NPs and alanine aminotransferase/aspartate aminotransferase values. Moreover, a meaningful correlation was detected between the rat's liver and spleen weight and ZnO-NPs doses. Furthermore, the histopathological analysis of rat's liver showed the individual cytotoxic properties of ZnO-NPs. Finally, the positive significant correlation was detected among the expression of Bax and P53 genes with ZnO-NPs. In addition, the negative correlation was demonstrated between the expression of Bcl-2 and ZnO-NPs.
In general, in the current study, the antitumor effects of ZnO-NPs were confirmed by the enhancement of P53 and Bax genes expression profile, which are indicated the apoptotic induction in HUH7 cell line. Moreover, we introduced a safe-clinical ZnO-NPs dosage, have antitumor effects.
由于具有细胞摄取和向生物系统输送效率等独特性质，纳米粒子被应用于各种临床前和临床应用中。本研究旨在研究氧化锌纳米粒子（ZnO-NPs）对大鼠肝脏和脾脏形态和功能的毒性影响，并阐明其安全治疗剂量。
将 28 只雌性瑞士白化大鼠（180-220g）和两种人肝细胞系（HepG2 和 HUH7）分别设计为体内和体外研究。用一定剂量的 ZnO-NPs 处理样本。分析大鼠肝脏形态和功能以及凋亡基因表达谱（Bax、Bcl-2 和 P53），以分别检测 ZnO-NPs 的细胞毒性和抗肿瘤作用。
结果表明，随着 ZnO-NPs 剂量的增加，丙氨酸氨基转移酶/天冬氨酸氨基转移酶值呈正相关。此外，大鼠肝脏和脾脏重量与 ZnO-NPs 剂量之间存在有意义的相关性。此外，大鼠肝脏的组织病理学分析显示了 ZnO-NPs 的个体细胞毒性特性。最后，检测到 Bax 和 P53 基因与 ZnO-NPs 之间存在正相关。此外，Bcl-2 与 ZnO-NPs 之间表现出负相关。
总的来说，在本研究中，通过增强 P53 和 Bax 基因表达谱证实了 ZnO-NPs 的抗肿瘤作用，这表明在 HUH7 细胞系中诱导了细胞凋亡。此外，我们引入了一种安全的临床 ZnO-NPs 剂量，具有抗肿瘤作用。
