Oxidative stress and inflammatory responses of rat following acute inhalation exposure to iron oxide nanoparticles.

In this research, we investigated the toxicity responses of rat following a continuous 4 h inhalation exposure of only the head and nose to iron oxide nanoparticles (Fe(3)O(4) NPs, size = 15-20 nm). The rats for the investigation were exposed to a concentration of 640 mg/m(3) Fe(3)O(4) NPs. Markers of lung injury and proinflammatory cytokines (interleukin-1β, tumor necrosis factor-α, and interleukin-6) in bronchoalveolar lavage fluid (BALF) and blood, oxidative stress in lungs, and histopathology were assessed on 24 h, 48 h, and 14 days of postexposure periods. Our results showed a significant decrease in the cell viability, with the increase in the levels of lactate dehydrogenase, total protein, and alkaline phosphatase in the BALF. Total leukocyte count and the percentage of neutrophils in BALF increased within 24 h of postexposure. Immediately following acute exposure, rats showed increased inflammation with significantly higher levels of lavage and blood proinflammatory cytokines and were consistent throughout the observation period. Fe(3)O(4) NPs exposure markedly increased malondialdehyde concentration, while intracellular reduced glutathione and antioxidant enzyme activities were significantly decreased in lung tissue within 24-h postexposure period. On histological observation, the lung showed an early activation of pulmonary clearance and a size-dependant biphasic nature of the Fe(3)O(4) NPs in causing the structural alteration. Collectively, our data illustrate that Fe(3)O(4) NPs inhalation exposure may induce cytotoxicity via oxidative stress and lead to biphasic inflammatory responses in Wistar rat.