Article

Particulate matter induced enhancement of inflammatory markers in the brains of apolipoprotein E knockout mice.

Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, California 91766-1854, USA.
Journal of Nanoscience and Nanotechnology (Impact Factor: 1.34). 08/2009; 9(8):5099-104. DOI: 10.1166/jnn.2009.GR07
Source: PubMed

ABSTRACT Exposure to air particulate matter (PM) present in urban environments have been shown to induce systemic prooxidant and proinflammatory effects in apolipoprotein E knockout (ApoE-/-) mice and proinflammatory central nervous system (CNS) effects in BALB/c mice. We hypothesize that ApoE-/- mice would exhibit a greater propensity to develop PM-induced CNS effects due to their greater susceptibility to CNS inflammation. We studied the brains of ApoE-/- mice exposed in a previous study to concentrated air particles of different sizes (fine vs. ultrafine) or filtered-air to evaluate the effect of PM exposure on the development of CNS proinflammatory effects in a genetically susceptible background. This was important because, although the use of nano-sized materials opens an exciting potential for their use as diagnostic or therapeutic tools, not much is known about the possible CNS toxicity of these particles. Neuroinflammation has been shown to exacerbate progression of neurodegeneration. Since the onset and progression of idiopathic forms of neurodegenerative disorders are likely to be multifactorial and involve gene-environment interactions, we determined the possibility of particles in ambient air pollution to enhance neuroinflammation. Our results indicate that in the brain, there was significant modulation in the activation of the transcription factors NF-kappaB and AP-1 after exposure to the ultrafine fractions. Levels of two pro-inflammatory cytokines (TNF-alpha and IL-1alpha) were also increased in the brain of exposed animals and this was independent of the size fraction of PM. Since inflammatory processes have been shown to contribute to the pathology associated with neurodegenerative diseases, it will be important to further evaluate the role ambient particles may play in the potentiation of existing CNS damage and progression of neurodegenerative disorders.

1 Follower
 · 
127 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Air pollution has persistently been the major cause of respiratory-related illness and death. Environmental pollutants such as diesel and petrol exhaust particles (PEPs) are the major contributors to urban air pollution. The aim of the present study was to characterize and investigate the in vitro cytotoxicity, oxidative stress, DNA damage and inflammation induced by PEPs. Cultured type II epithelium cells (human A549 lung cells) and alveolar macrophages (murine RAW 264.7 cells) were exposed to control, vehicle control and to different concentrations of PEPs for up to 24h. Each treatment was evaluated by cell viability, cytotoxicity, oxidative stress, DNA damage and inflammatory parameters. Overall in vitro studies demonstrated that both cell lines showed similar patterns in response to the above studies induced by petrol exhaust nanoparticles (PENPs). Vehicle control showed no changes compared with the control. In both cell lines, significant changes at the dose of 20 and 50μg/mL (A549 cell lines) and 10and 20μg/mL (macrophages) for PENPs were found. The reactive oxygen species production in both cell lines shot up in minutes, reached the maximum within an hour and came down after 4h. Hence, exposure to PENPs resulted in dose-dependent toxicity in cultured A549 cells and RAW 264.7 cells and was closely correlated to increased oxidative stress, DNA damage and inflammation.
    Environmental Toxicology and Pharmacology 08/2014; 38(2):518-530. DOI:10.1016/j.etap.2014.08.003 · 1.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inhalation of airborne particulate matter (PM) derived from urban traffic is associated with pathology in the arteries, heart, and lung; effects on brain are also indicated but are less documented. We evaluated rodent brain responses to urban nanoscale (< 200 nm) PM (nPM). Ambient nPM collected near an urban freeway was transferred to aqueous suspension and reaerosolized for 10-week inhalation exposure of mice or directly applied to rat brain cell cultures. Free radicals were detected by electron paramagnetic resonance in the nPM 30 days after initial collection. Chronic inhalation of reaerosolized nPM altered selected neuronal and glial activities in mice. The neuronal glutamate receptor subunit (GluA1) was decreased in hippocampus, whereas glia were activated and inflammatory cytokines were induced [interleukin-1α (IL-1α), tumor necrosis factor-α (TNFα)] in cerebral cortex. Two in vitro models showed effects of nPM suspensions within 24-48 hr of exposure that involved glutamatergic functions. In hippocampal slice cultures, nPM increased the neurotoxicity of NMDA (N-methyl-d-aspartic acid), a glutamatergic agonist, which was in turn blocked by the NMDA antagonist AP5 [(2R)-amino-5-phosphonopentanoate]. In embryonic neuron cultures, nPM impaired neurite outgrowth, also blocked by AP5. Induction of IL-1α and TNFα in mixed glia cultures required higher nPM concentrations than did neuronal effects. Because conditioned media from nPM-exposed glia also impaired outgrowth of embryonic neurites, nPM can act indirectly, as well as directly, on neurons in vitro. nPM can affect embryonic and adult neurons through glutamatergic mechanisms. The interactions of nPM with glutamatergic neuronal functions suggest that cerebral ischemia, which involves glutamatergic excitotoxicity, could be exacerbated by nPM.
    Environmental Health Perspectives 04/2011; 119(7):1003-9. DOI:10.1289/ehp.1002973 · 7.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiologic and clinical studies have linked elevated concentrations of ambient ultrafine particles (UFPs) to adverse health effects. In particular, has been demonstrated an association between UFPs exposure and occurrence of acute respiratory infections, lung cancer, chronic chronic obstructive pulmonary diseases and cardiovascular diseases. Although the biological mechanisms behind these associations are not fully understood, the results of in vitro toxicological research have shown that UFPs induces several types of adverse cellular effects, including cytotoxicity, mutagenicity, DNA oxidative damage and stimulation of proinflammatory cytokine production. In this reviewer are summarized the results of the recent epidemiological and toxicological studies on adverse health effects from exposure to UFPs.
    Giornale italiano di medicina del lavoro ed ergonomia 32(4 Suppl):348-51.