The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level.

Department of Animal Physiology and Immunology Faculty of Science Masaryk University Brno 625 00 Czech Republic

Department of Histology and Embryology Faculty of Medicine Masaryk University Brno 625 00 Czech Republic

Department of Pathological Morphology and Parasitology Faculty of Veterinary Medicine University of Veterinary and Pharmaceutical Sciences Brno 612 42 Czech Republic

Institute of Analytical Chemistry v v i Czech Academy of Sciences Veveř and 237; 97 Brno 602 00 Czech Republic

Institute of Animal Physiology and Genetics v v i Czech Academy of Sciences Brno 602 00 Czech Republic

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Sub-chronic inhalation of lead oxide nanoparticles revealed their broad distribution and tissue-specific subcellular localization in target organs