Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

Abstract

Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe.

The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

“…[46][47][48] It has been shown that a 4-week inhalation exposure to DECe in rats induced an increase of tissue factor, but not in PAI-1 concentration. 19 The discrepancy between the latter study showing the absence of an increase of PAI-1 …”

“…16,17 It is well-established that particulate air pollution and some engineered NPs affect the cardiovascular system either through inflammatory mediators produced in the lungs and released into the circulation or via their ability to cross the alveolar-capillary barrier and reach the cardiovascular system. 5,18 Since CeO 2 NPs have been shown to cross the alveolar-capillary barrier to reach extrapulmonary sites 19,20 and cause lung inflammation, 14,15,20 the present study hypothesized that these NPs can plausibly interact with the circulating platelets and vasculature and induce thrombotic events. This has not been investigated before, and, consequently, the aim of this study was to assess the acute (24 hours) effect of CeO 2 NPs on pulmonary and systemic inflammation and oxidative stress in mice and to evaluate their effects on coagulation in vivo and in vitro.…”

“…24,37 It has been recently demonstrated that aortic RNA expression of endothelial nitric oxide synthase, tissue factor, and TNFα were significantly increased by 4-week inhalation exposure to whole CeO 2 NPs added to diesel fuel (DECe) or gas-phase components of DECe. 19 However, the latter results are in conflict with the data from another study which implied that the addition of a Ce-based fuel-borne catalyst may decrease the atherosclerotic burden induced by exposure to diesel fuel in atherosclerosis-prone mice. 43 Also, it has been shown that CeO 2 NPs improve microvascular reactivity in hypertensive rats.…”

“…19,49 This study wanted to verify whether the CeO 2 NPs can directly induce platelet aggregation and affect PT and aPTT in vitro. The concentration of 1 μg/mL CeO 2 NPs used here in vitro is similar to that employed recently to induce prothrombotic effects of DEPs in vitro.…”

A book review; "Rare earth elements in human and environmental health; at the crossroads between toxicity and safety"

“…The third and most widespread source of REE-related air and soil pollution may refer to the global use of nCeO 2 as catalytic additives in diesel fuel. The limited number of publications in the literature thus far points to nCeO 2 as components of diesel exhaust particulate matter (Cassee et al 2011;2012;Ma et al 2014;Snow et al 2014), thus prompting investigations on the relevance and possible health implications of diesel exhaust particulate matter following human exposure to these elements at work or in the environment. Stunted animal growth and decreased chlorophyll production are among the forms of damage to animals and plants, respectively, that have been reviewed in separate chapters (4, 6, and 7; by Philippe J. Thomas, Giovanni Pagano, and Rahime Oral).…”