Titanium oxide nanoparticle instillation induces inflammation and inhibits lung development in mice

Abstract

Nanoparticles are used in an increasing number of biomedical, industrial, and food applications, but their safety profiles in developing organisms, including the human fetus and infant, have not been evaluated. Titanium oxide (TiO(2)) nanoparticles, which are commonly used in cosmetics, sunscreens, paints, and food, have been shown to induce emphysema and lung inflammation in adult mice. We hypothesized that exposure of newborn mice to TiO(2) would induce lung inflammation and inhibit lung development. C57BL/6 mice were exposed to TiO(2) (anatase; 8-10 nm) nanoparticles by intranasal instillation as a single dose on postnatal day 4 (P4) or as three doses on postnatal days 4, 7, and 10 (each dose = 1 μg/g body wt). Measurements of lung function (compliance and resistance), development (morphometry), inflammation (histology; multiplex analysis of bronchoalveolar lavage fluid for cytokines; PCR array and multiplex analysis of lung homogenates for cytokines) was performed on postnatal day 14. It was observed that a single dose of TiO(2) nanoparticles led to inflammatory cell influx, and multiple doses led to increased inflammation and inhibition of lung development without significant effects on lung function. Macrophages were noted to take up the TiO(2) nanoparticles, followed by polymorphonuclear infiltrate. Multiple cytokines and matrix metalloproteinase-9 were increased in lung homogenates, and VEGF was reduced. These results suggest that exposure of the developing lung to nanoparticles may lead to ineffective clearance by macrophages and persistent inflammation with resulting effects on lung development and may possibly impact the risk of respiratory disorders in later life.

Recent advances in the mechanisms of lung alveolarization and the pathogenesis of bronchopulmonary dysplasia

“…Nanoparticles are present in cosmetics, paint, sunscreens, and food (287). Using titanium oxide nanoparticles (average diameter 8 -10 nm), Ambalavanan and coworkers (22) reported that exposure of mouse pups at P4 to single or multiple doses of nanoparticles provoked an increase in the expression of proinflammatory mediators and blunted lung development (assessed at P14; by MLI and RAC). In a related study, Chan and coworkers (60) described the muted expression of Cyp1A1, a cytochrome P-450 superfamily member, in neonatal, but not adult rats, after exposure to ultrafine particular matter, which is a key component of vehicle exhaust.…”

The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway

“…Although various toxicities of nano-TiO 2 have been studied with different cell and animal models, [20][21][22][23][24] the research on their possible impacts on the cardiovascular system is relatively limited, especially the underlying toxicological mechanisms remain unclear. 2,25 Thus, it is meaningful to deeply study the effects of nano-TiO 2 on the cardiovascular system and the underlying biological mechanisms, which will in turn provide scientific data for the risk assessment and developing novel strategies to mitigate their toxicities.…”

TiO2 Nanoparticles Induce Lung Fibrosis and Proteinosis through Influence on Matrix Metalloproteinase Expression

“…The coefficients of tissue are shown in the table [2]. It was defined as grams (wet weight of tissue/body weight).…”

“…Titanium dioxide nanoparticles (TiO 2 NP), which generally utilized in prettifying, paints, sunscreens, and nutrition, induced emphysema and lung sore in mice (2). TiO 2 particles are not immunologically active and may be an essential supplement in beat normal gut cell hypo-responsiveness to endogenous luminal molecules.…”