Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia; A.R. Al-Jeraisy Chair for DNA Research, Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
Int J Biol Macromol. 2017 Dec;105(Pt 1):228-237. doi: 10.1016/j.ijbiomac.2017.07.032. Epub 2017 Jul 6.
The unique properties of nickel oxide nanoparticles (NiO-NPs) distinguish it from traditional nickel containing materials, and enable its industrial application as an advanced nanomaterial. Despite the benefits, the in vivo toxicological studies on NiO-NPs have been mainly focused on its pulmonary pathology. However, NiO-NPs exposure via oral route and its subsequent toxic effects in exposed animals are still lacking. Hence, we evaluated the NiO-NPs oral toxicity in male Wistar rats. NiO-NPs induced significant increase in chromosomal aberrations (CAs), micronuclei (MN) formation and, DNA damage in rats. Flow cytometric analysis showed apoptosis, ROS generation and dysfunction of mitochondrial membrane potential (ΔΨm). Imbalance of antioxidant enzymes, along with histological alterations was found in liver. Taking together, these results unequivocally suggested that NiO-NPs induced toxicity was through cyto-genetic alterations, oxidative stress, apoptosis and liver toxicity. The western blotting data validated the interplay of p53 and MAPKAPK-2 signalling via activation of caspases 8, 3, cyto c, pro-apoptotic bax and anti-apoptotic bcl-2 proteins.
氧化镍纳米粒子（NiO-NPs）的独特性质使其有别于传统的含镍材料，并使其能够作为一种先进的纳米材料应用于工业领域。尽管 NiO-NPs 有诸多益处，但目前对其体内毒理学的研究主要集中在其肺部病理方面。然而，通过口服途径暴露于 NiO-NPs 及其随后对暴露动物的毒性效应仍不清楚。因此，我们评估了 NiO-NPs 对雄性 Wistar 大鼠的口服毒性。NiO-NPs 可导致大鼠染色体畸变（CAs）、微核（MN）形成和 DNA 损伤显著增加。流式细胞术分析显示细胞凋亡、ROS 生成和线粒体膜电位（ΔΨm）功能障碍。还发现肝脏中的抗氧化酶失衡以及组织学改变。综上所述，这些结果明确表明 NiO-NPs 诱导的毒性是通过细胞遗传学改变、氧化应激、细胞凋亡和肝毒性产生的。Western blot 数据分析验证了 p53 和 MAPKAPK-2 信号通路的相互作用，通过激活半胱天冬酶 8、3、细胞色素 c、促凋亡 bax 和抗凋亡 bcl-2 蛋白。
