Cardiopulmonary toxicity of pulmonary exposure to occupationally relevant zinc oxide nanoparticles

Abstract

Exposure to zinc oxide (ZnO) metal fumes is linked to adverse human health effects; however, the hazards of ZnO nanoparticles (ZnONPs) remain unclear. To determine pulmonary exposure to occupationally relevant ZnONPs cause cardiopulmonary injury, Sprague-Dawley rats were exposed to ZnONPs via intratracheal (IT) instillation and inhalation. The relationship between intrapulmonary zinc levels and pulmonary oxidative-inflammatory responses 72 h after ZnONP instillation was determined in bronchoalveolar lavage fluid (BALF). Instilled ZnONPs altered zinc balance and increased the levels of total cells, neutrophils, lactate dehydrogenase (LDH) and total protein in BALF and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in blood after 72 h. The ZnONPs accumulated predominantly in the lungs over 24 h, and trivial amounts of zinc were determined in the heart, liver, kidneys and blood. Furthermore, the inflammatory-oxidative responses induced by occupationally relevant levels of 1.1 and 4.9 mg/m³ of ZnONP inhalation for 2 weeks were determined in BALF and blood at 1, 7 and 30 days post-exposure. Histopathological examinations of the rat lungs and hearts were performed. Inhalation of ZnONP caused an inflammatory cytological profile. The total cell, neutrophil, LDH and total protein levels were acutely increased in the BALF, and there was an inflammatory pathology in the lungs. There were subchronic levels of white blood cells, granulocytes and 8-OHdG in the blood. Cardiac inflammation and the development of fibrosis were detected 7 days after exposure. Degeneration and necrosis of the myocardium were detected 30 days after exposure. The results demonstrate that ZnONPs cause cardiopulmonary impairments. These findings highlight the occupational health effects for ZnONP-exposed workers.

Keywords::

• cardiac injury
• inflammation
• oxidative stress
• zinc ion
• zinc oxide nanoparticle

Acknowledgements

The authors wish to thank H.-M. Chein, Y.-J. Lin and J.-Y. Lui for the technical assistance of this research.

Declaration of interest

H.-C. Chuang contributed substantially to the completion of interpretation of the data and the manuscript. H.-T. Juan contributed substantially to the completion of the study. Y.-H. Yan and H.-C. Chen contributed to the interpretation of the data. C.-N. Chang, T.-H. Yuan and Y.-H. Hwang contributed to the chemical analysis. J.-S. Wang and C.-H. Lee contributed to the histopathological analyses. T.-J. Cheng contributed substantially to the concept, the design and the completion of the study, the statistical analyses and critically revising the manuscript for important intellectual content. All authors have read and approved the final manuscript. This study was founded by the National Science Council of Taiwan (grant number 99-2621-M-002-006 and 100-2621-M-002-005). The authors declare that they have no conflict of interest.