Biochemistry Laboratory, Animal Facility, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow 226028, Uttar Pradesh, India.
Water Analysis Laboratory, Nanotherapeutics and Nanomaterials Toxicology Group, CSIR-Indian Institute of Toxicology Research, (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226001, Uttar Pradesh, India.
J Trace Elem Med Biol. 2019 Mar;52:270-287. doi: 10.1016/j.jtemb.2019.01.008. Epub 2019 Jan 14.
Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanomaterials. Following oral exposure, these NPs can accumulate in various organs and induce the toxicity due to their physiochemical characteristics. In present study to reduce the toxicity, surface engineered ZnO NPs (c-ZnO NPs) were in-situ synthesized by using polyacrylamide grafted guar gum (PAm-g-GG) polymer in alkaline media. Further, the comparative effect of bared ZnO NPs (b-ZnO NPs) and c-ZnO NPs were assessed on secondary target organ liver and kidneys of Swiss mice at doses of 10, 50 and 300 mg/kg following 28 days repeated oral treatment. The b-ZnO NPs were incited severe damages in liver and kidney tissue than c-ZnO NPs as seen by transmission electron microscopy and histopathology. The increased levels of serum biomarkers (AST, ALT, ALP, creatinine, uric acid, and urea) were also observed, that remarking a disturbance in the function of liver and kidney. After sub-acute oral treatment of b-ZnO NPs, the hepatic pro-inflammatory cytokines (IL-6, TNF-α, and MMP-9) were up-regulated that causes the activation of acute phase response (APR). We also observed significantly increased in expression of hepatic acute phase proteins (hepcidin and haptoglobin) and altered interlinked iron (Fe) signaling biomarkers (hephaestin, TF, TFR-1, LDH, and ferroportin). This study emphasizes that exposure to ZnO NPs may cause inflammation mediated APR through ultra-structural damage of tissue that could escort the progression of anemia. Nevertheless, the capping with PAm-g-GG in c- ZnO NPs has reduced the toxicity by altering the surface reactive property of ZnO NPs.
氧化锌纳米粒子（ZnO NPs）是应用最广泛的纳米材料之一。经口服暴露后，由于其物理化学特性，这些 NPs 可在各种器官中积累并引发毒性。在本研究中，为了降低毒性，在碱性介质中使用接枝有聚丙烯酰胺的瓜尔胶（PAm-g-GG）聚合物原位合成了表面修饰的 ZnO NPs（c-ZnO NPs）。进一步，在 28 天重复口服处理后，在剂量为 10、50 和 300mg/kg 时，评估了 bare ZnO NPs（b-ZnO NPs）和 c-ZnO NPs 对瑞士小鼠的次级靶器官肝脏和肾脏的比较作用。透射电子显微镜和组织病理学观察到，b-ZnO NPs 比 c-ZnO NPs 更能激发肝脏和肾脏组织的严重损伤。还观察到血清生物标志物（AST、ALT、ALP、肌酐、尿酸和尿素）水平升高，表明肝脏和肾脏功能受到干扰。在 b-ZnO NPs 的亚急性口服处理后，肝促炎细胞因子（IL-6、TNF-α 和 MMP-9）上调，导致急性相反应（APR）的激活。我们还观察到肝脏急性期蛋白（hepcidin 和 haptoglobin）的表达显著增加，并改变了相互关联的铁（Fe）信号生物标志物（hephaestin、TF、TFR-1、LDH 和 ferroportin）。本研究强调，暴露于 ZnO NPs 可能会通过组织的超微结构损伤引起炎症介导的 APR，从而导致贫血的进展。然而，在 c-ZnO NPs 中用 PAm-g-GG 进行包封，通过改变 ZnO NPs 的表面反应性降低了毒性。
