Pulmonary Toxicity Assessment of Aluminum Oxide Nanoparticles via Nasal Instillation Exposure

Abstract

Objective: The use of nanoparticle products is expected to present a potential harmful effect on consumers. Also, the lack of information regarding inhaled nanoparticles may pose a serious problem. In this study, we addressed this issue by studying pulmonary toxicity after nasal instillation of Al-NPs in SD rats. Methods: The animals were exposed to Al-NPs at 1 mg/kg body weight (low dose), 20 mg/kg body weight (medium dose) and 40 mg/kg body weight (high dose). To determine pulmonary toxicity, bronchoalveolar lavage (ts.AnBAL) fluid analysis and histopathological examination were conducted in rats. In addition, cell viability was investigated at 24 hours after the treatment with Al-NPs. Results: BAL fluid analysis showed that total cells (TC) count and total protein (TP) concentrations increased significantly in all treatment groups, approximately two to three times. Also, lactate dehydrogenase (LDH) and cytokines such as TNF-alpha and IL-6 dose-dependently increased following nasal instillation of Al-NPs. However, polymorphonuclear leukocytes (PMNs) levels showed no significant changes in a dose dependant manner in BAL fluid. In the cytotoxicity analysis, the treatment of Al-NPs significantly and dose-dependently induced cell viability loss (20 to 30%) and damage of cell membrane (5 to 10%) in rat normal lung epithelial cells (L2). Conclusions: Our results suggest that inhaled Al-NPs in the lungs may be removed quickly by alveolar macrophages with minimal inflammatory reaction, but Al-NPs have the potential to affect lung permeability. Therefore, extensive toxicity evaluations of Al-NPs are required prior to their practical application as consumer products.

Twenty-Eight-Day Repeated Inhalation Toxicity Study of Aluminum Oxide Nanoparticles in Male Sprague-Dawley Rats

“…More specifically, this was reflected by an increase in the absolute and relative lung weights in the 5 mg/m 3 group during exposure. This was in contrast to a previous study where intratracheal instillation of Al 2 O 3 NPs induced no changes in organ weight ( 7 ).…”

“…In addition, hematology and serum biochemistry results showed that there were no systemic effects related to the exposure to Al 2 O 3 NPs. Kwon et al showed similar results in SD rats, although the exposure to Al 2 O 3 NPs was through intratracheal instillation ( 7 ). Although no systemic effects were observed in the present study after Al 2 O 3 NP exposure, including body weight loss and clinical symptoms, the toxicological effects related to Al 2 O 3 NPs exposure were mainly observed in the lungs.…”

“…The levels of LDH, IL-6, and TNF-α increased significantly in the 5 mg/m 3 group during exposure; additionally, LDH and IL-6 concentrations increased significantly in the 5 mg/m 3 group during recovery. By contrast, Kwon et al ( 7 ) showed there were no significant changes in LDH, IL-6, and TNF-α levels in BALF, although they tended to increase in the middle and/or high dose-exposed groups. These opposing results might be attributed to the difference in the amount and/or particle size of Al 2 O 3 NPs that reach deep into the lungs via inhalation compared to tracheal instillation.…”

“…In the BALF analysis, we observed a significant increase in total cell counts, PMNs, and lymphocytes during exposure, whereas only PMNs increased during recovery. Kwon et al similarly reported an increase in the counts of total cells, PMNs, and lymphocytes after intratracheal instillation of Al 2 O 3 NPs at 1, 20, and 40 mg/kg ( 7 ). The levels of LDH, IL-6, and TNF-α increased significantly in the 5 mg/m 3 group during exposure; additionally, LDH and IL-6 concentrations increased significantly in the 5 mg/m 3 group during recovery.…”

“…Li et al demonstrated that Al 2 O 3 NPs induced mitochondrial-dependent apoptosis and oxidative stress in vitro and in vivo . Additionally, Kwon et al evaluated the cytotoxicity of Al 2 O 3 NPs in rat lung epithelial cells ( 3 , 7 ) and demonstrated that intratracheal instillation of Al 2 O 3 NPs could trigger an inflammatory response in the lungs. Generally, NPs can be inhaled more deeply than large particles, leaving sediment on the surface of the trachea, bronchi, and alveoli.…”