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/m(3) 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.

Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study

“…[24][25][26] We have previously shown that a 14-day continuous exposure of rats to ZnONPs caused significant cardiopulmonary impairment observed after a 28-day follow-up period. 9 However, the mechanisms underlying the acute and subacute effects of ZnONP exposure may be different. Also, a previous study showed that there was 0.14% of 65 ZnONPs remaining in the lungs after 28 days post-IT exposure.…”

“…1 In a rat model, pulmonary impairment and degeneration as well as necrosis of the myocardium were detected after 30 days of repeated exposure to ZnONPs. 9 Time-dependent responses, including mitochondrial dysfunction and oxidative stress, were observed in rat alveolar epithelial cell monolayers. 10 Together, these results imply that the health effects of ZnONP exposure may depend on the time following exposure.…”

“…9 Briefly, the ZnONPs were investigated via adhesion to 12 mm carbon adhesive tabs on 13 mm aluminum SEM stubs. The SEM stubs were coated with platinum (Pt), with an average thickness of 10 nm using a sputter coater.…”

Physiologically based pharmacokinetic modeling of zinc oxide nanoparticles and zinc nitrate in mice

“…Yet, the simulation of 65 Zn(NO) 3 was well fitted with the experimental data. Therefore, it is likely that 65 ZnO NPs gradually decompose into zinc ion after 7 days.…”

“…1 The biodistribution of NPs might markedly influence their biological effects in vivo, such as in inflammatory and oxidative responses related to cardiopulmonary toxicity. 2,3 Zinc oxide nanoparticles (ZnO NPs) are commonly used in sunscreens in particle sizes ranging from 70 nm to 100 nm because of strong ultraviolet absorptive properties. ZnO NPs also have potential application in the delivery of therapeutic agents for tumors and autoimmune diseases.…”