Environmental Health and Toxicology Lab, Department of Environmental Sciences, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India.
Vascular Research Laboratory, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu, India.
Chem Biol Interact. 2022 Jan 5;351:109719. doi: 10.1016/j.cbi.2021.109719. Epub 2021 Oct 23.
The precise toxico-pathogenic effects of zinc oxide nanoparticles (ZnO-NPs) on the cardiovascular system under normal and cardiovascular disease (CVD) risk factor milieu are unclear. In this study, we have investigated the dose-dependent effects of ZnO-NPs on developing chicken embryo and cell culture (H9c2 cardiomyoblast, HUVEC and aortic VSMC) models. In addition, the potentiation effect of ZnO-NPs on simulated risk factor conditions was evaluated using; 1. Reactive oxygen species (ROS) induced cardiac remodeling, 2. Angiotensin-II induced cardiac hypertrophy, 3. TNF-α induced HUVEC cell death and 4. Inorganic phosphate (Pi) induced aortic VSMC calcification models. The observed results illustrates that ZnO-NPs exposure down regulates vascular development and elevates oxidative stress in heart tissue. At the cellular level, ZnO-NPs exposure reduced the cell viability and increased the intracellular ROS generation, lipid peroxidation and caspase-3 activity in a dose-dependent manner in all three cell types. In addition, ZnO-NPs exposure significantly suppressed the endothelial nitric oxide (NO) generation, cardiac Ca - ATPase activity and enhanced the cardiac mitochondrial swelling. Moreover, inhibition of p38 MAPK and JNK signaling pathways influence the cytotoxicity. Overall, ZnO-NPs exposure affects the cardiovascular system under normal conditions and it exacerbates the cardiovascular pathogenesis under selected risk factor milieu.
氧化锌纳米粒子（ZnO-NPs）对心血管系统在正常和心血管疾病（CVD）风险因素环境下的精确毒理作用尚不清楚。在这项研究中，我们研究了 ZnO-NPs 对发育中的鸡胚和细胞培养（H9c2 心肌细胞、HUVEC 和主动脉 VSMC）模型的剂量依赖性影响。此外，还使用以下方法评估了 ZnO-NPs 对模拟风险因素条件的增强作用：1. 活性氧（ROS）诱导的心脏重构，2. 血管紧张素-II 诱导的心肌肥大，3. TNF-α诱导的 HUVEC 细胞死亡，4. 无机磷（Pi）诱导的主动脉 VSMC 钙化模型。观察到的结果表明，ZnO-NPs 暴露会下调血管发育并增加心脏组织中的氧化应激。在细胞水平上，ZnO-NPs 暴露以剂量依赖性方式降低了三种细胞类型的细胞活力，并增加了细胞内 ROS 的产生、脂质过氧化和 caspase-3 活性。此外，ZnO-NPs 暴露还显著抑制了内皮型一氧化氮（NO）的产生、心脏 Ca-ATPase 活性，并增强了心脏线粒体肿胀。此外，抑制 p38 MAPK 和 JNK 信号通路会影响细胞毒性。总体而言，ZnO-NPs 暴露会影响正常情况下的心血管系统，并在选定的风险因素环境下加剧心血管发病机制。
