Effects of short-term exposure to titanium dioxide on pulmonary endothelial function
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Nanotechnology, the manipulation and manufacturing of particles less than 100 nm in size, is at the forefront of scientific research. However, there is evidence that the size-dependent properties of nanoparticles give rise to high toxicity levels. Studies have shown that exposure to inhaled nanoparticles, including titanium dioxide (Ti02), is associated with increased reactive oxygen species (ROS), leading to endothelial dysfunction. To date, most studies on nanoparticle toxicity are based on the effects on cells after particles have been internalized. However, we hypothesized that internalization is not necessary to cause dysfunction. To test our hypothesis, we examined changes in endothelial dilation in response to a vasodilator, ionomycin. We expected percent vasodilation to be lower in groups treated with Ti02, indicating dysfunction. Particle exposure was accomplished using two separate doses ofTi02 (0.05% v/v, 0.1 % v Iv) using the isolated perfused lung preparation of 17 rat lungs. Lungs were exposed for 1 hour, a time period over which we expected no internalization of Ti02. We observed an increase in pulmonary arterial resistance after the addition ofTi02 to the perfusate, which we can attribute to an increase in shear stress. We found a significant increase in percent dilation with increasing amounts of ionomycin; however, our data showed no significant difference in percent dilation between groups at each individual dose of ionomycin. Therefore, our initial hypothesis was not supported, and we concluded that internalization of Ti02 may indeed be necessary to cause pulmonary endothelial dysfunction. Future studies should analyze the localization of Ti02 within the endothelial cells to conclusively determine whether the particles were internalized or not, and should also examine the effects of other nanoparticles on endothelial function.