Repeated intratracheal instillation of zinc oxide nanoparticles induced pulmonary damage and a systemic inflammatory response in cynomolgus monkeys

Autor:	Seung Hyeun Lee, Junhee Park, Jae Woo Cho, Gwang Hee Lee, Hyun Ji Lim, Jeongah Song, Eun-Jung Park, Cheolho Yoon, Soo Nam Kim, Dong Wan Kim, Hong Soo Lee, Min-Sung Kang, Inhee Choi
Rok vydání:	2021
Předmět:	Programmed cell death Globulin Biomedical Engineering Chromosomal translocation 02 engineering and technology 010501 environmental sciences Pharmacology Toxicology 01 natural sciences Fibrin medicine Animals Lung 0105 earth and related environmental sciences biology business.industry C-reactive protein Albumin 021001 nanoscience & nanotechnology Systemic Inflammatory Response Syndrome Macaca fascicularis medicine.anatomical_structure biology.protein Biomarker (medicine) Nanoparticles Zinc Oxide 0210 nano-technology business
Zdroj:	Nanotoxicology. 15(5)
ISSN:	1743-5404
Popis:	Recently, some researchers have demonstrated that inhaled zinc oxide nanoparticles (ZnONPs) induce an acute systemic inflammatory response in workers. Considering nonhuman primates are preferably considered an animal model for translational research due to their proven similarity with humans in terms of genetics and physiology, we intratracheally instilled ZnONPs to cynomolgus monkey for 14 days and identified the toxic mechanism and bioaccumulation. ZnONPs were rapidly ionized or aggregated in a simulated pulmonary fluid, and they attracted neutrophils to the lungs and increased the pulmonary level of inflammatory mediators. Additionally, thickened alveolar walls, fibrin clots, and hemorrhages were observed in the lungs of the monkeys instilled with the higher dose accompanied by cell debris in the alveolar ducts and alveoli. Dark-field microscopy images revealed translocation of ZnONPs into other tissues accompanied by an increase in the relative weight of livers to body weight. In addition, when instilled at the higher dose, the albumin/globulin ratio notably decreased compared to the control, whereas the C-reactive protein (CRP) level was significantly elevated. ZnONPs also clearly induced apoptotic cell death in a 24 h exposure to alveolar macrophages. Taken together, part of inhaled ZnONPs may be ionized in the lung, resulting in acute toxic effects, including cell death and tissue damage, and the rest may move to other tissues in the form of particles, causing a systemic inflammatory response. Based on the proven evidence among workers, we also suggest that the CRP level can be recommended as a biomarker for ZnONPs-induced adverse health effects.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b5bbbcd6656b78031665b37ddda5626 https://pubmed.ncbi.nlm.nih.gov/33870832 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.