title: The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice.
abstract: BACKGROUND
  Cerium oxide (CeO(2)) nanoparticles improve the burning efficiency of fuel, however, little is known about health impacts of altered emissions from the vehicles.
  
  
  METHODS
  Atherosclerosis-prone apolipoprotein E knockout (ApoE(-/-)) mice were exposed by inhalation to diluted exhaust (1.7 mg/m(3), 20, 60 or 180 min, 5 day/week, for 4 weeks), from an engine using standard diesel fuel (DE) or the same diesel fuel containing 9 ppm cerium oxide nanoparticles (DCeE). Changes in hematological indices, clinical chemistry, atherosclerotic burden, tissue levels of inflammatory cytokines and pathology of the major organs were assessed.
  
  
  RESULTS
  Addition of CeO(2) to fuel resulted in a reduction of the number (30%) and surface area (10%) of the particles in the exhaust, whereas the gaseous co-pollutants were increased (6-8%). There was, however, a trend towards an increased size and complexity of the atherosclerotic plaques following DE exposure, which was not evident in the DCeE group. There were no clear signs of altered hematological or pathological changes induced by either treatment. However, levels of proinflammatory cytokines were modulated in a brain region and liver following DCeE exposure.
  
  
  CONCLUSIONS
  These results imply that addition of CeO(2) nanoparticles to fuel decreases the number of particles in exhaust and may reduce atherosclerotic burden associated with exposure to standard diesel fuel. From the extensive assessment of biological parameters performed, the only concerning effect of cerium addition was a slightly raised level of cytokines in a region of the central nervous system. Overall, the use of cerium as a fuel additive may be a potentially useful way to limit the health effects of vehicle exhaust. However, further testing is required to ensure that such an approach is not associated with a chronic inflammatory response which may eventually cause long-term health effects.
authors.affiliation: National Institute for Public Health and the Environment, PO box 1, 3720 BA Bilthoven, The Netherlands. flemming.cassee@rivm.nl
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
authors.forename: Arezoo
authors.initials: A
authors.lastname: Campbell
authors.forename: A John F
authors.initials: AJ
authors.lastname: Boere
authors.forename: Steven G
authors.initials: SG
authors.lastname: McLean
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.forename: Petra
authors.initials: P
authors.lastname: Krystek
authors.forename: Ilse
authors.initials: I
authors.lastname: Gosens
authors.forename: Mark R
authors.initials: MR
authors.lastname: Miller
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001921:Brain / Q000276:immunology; D002563:Cerium / Q000633:toxicity*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D007150:Immunohistochemistry; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D011897:Random Allocation; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D006454:Hemoglobins; D052638:Particulate Matter; D001335:Vehicle Emissions; D002563:Cerium; C030583:ceric oxide