The adverse pathophysiological effects of outdoor air pollution on the body tissues
Long-term exposure to outdoor air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. There are many published studies about the pathophysiological mechanisms involved in response of the body tissues to outdoor air pollution exposure. The aim of our review was to investigate the problem of outdoor air pollution and health effects of pathological mechanisms, with specific goal to point out public health intervention strategies based upon a clearer understanding of pathophysiological mechanisms of outdoor air pollution. A systematic literature review was carried out in two bibliographic databases, Science Direct and PubMed, in the period from January 1995 to December 2015. We conducted a systematic analysis of 95 studies, 43 of them being review studies and 52 original studies. The systematic analysis was done in three steps, for each body tissue separately (respiratory diseases, cardiovascular diseases, neurologic diseases and diabetes mellitus). This insight into literature review may help foster more effective preventive measures at the public health level as well as potential intervention strategies based upon a clearer understanding of the involved pathways.
Faustini A, Stafoggia M, Colais P, Berti G, Bisanti L, Cadum E, et al. EpiAir Collaborative Group. Air pollution and multiple acute respiratory outcomes. Eur Respir J. 2013 Aug;42(2):304–13.
Raaschou-Nielsen O, Andersen ZJ, Beelen R, Samoli E, Stafoggia M, Weinmayr G, et al. Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Lancet Oncol. 2013 Aug;14(9):813–22.
Pope CA 3rd, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, et al. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA. 2002 Mar;287(9):1132–41.
Nishimura KK, Galanter JM, Roth LA, Oh SS, Thakur N, Nguyen EA, et al. Early-life air pollution and asthma risk in minority children. The GALA II and SAGE II studies. Am J Respir Crit Care Med. 2013 Aug;188(3):309–18.
Global l Initiative for Chronic Obstructive Lung Disease . Available from: http://www.goldcopd.org.
Yamamoto SS, Phalkey R, Malik AA. A systematic review of air pollution as a risk factor for cardiovascular disease in South Asia: limited evidence from India and Pakistan. Int J Hyg Environ Health. 2014 Mar;217(2–3):133–44.
Brucker N, Charão MF, Moro AM, Ferrari P, Bubols G, Sauer E, et al. Atherosclerotic process in taxi drivers occupationally exposed to air pollution and co-morbidities. Environ Res. 2014 May;131:31–8.
Foraster M, Basagaña X, Aguilera I, Rivera M, Agis D, Bouso L, et al. Association of long-term exposure to traffic-related air pollution with blood pressure and hypertension in an adult population-based cohort in Spain (the REGICOR study). Environ Health Perspect. 2014 Apr;122(4):404–11.
Dong GH, Qian ZM, Xaverius PK, Trevathan E, Maalouf S, Parker J, et al. Association between long-term air pollution and increased blood pressure and hypertension in China. Hypertension. 2013 Mar;61(3):578–84.
Wu S, Deng F, Huang J, Wang H, Shima M, Wang X, et al. Blood pressure changes and chemical constituents of particulate air pollution: results from the healthy volunteer natural relocation (HVNR) study. Environ Health Perspect. 2013 Jan;121(1):66–72.
Block ML, Calderón-Garcidueñas L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. 2009 Sep;32(9):506–16.
Craig L, Brook R, Chiotti Q, et al. Air pollution and public health: a guidance document for risk managers. Journal of Toxicology and Environmental health. 2008;(71)9,10:588–698.
Brook RD, Jerrett M, Brook JR, Bard RL, Finkelstein MM. The relationship between diabetes mellitus and traffic-related air pollution. J Occup Environ Med. 2008 Jan;50(1):32–8.
Krämer U, Herder C, Sugiri D, Strassburger K, Schikowski T, Ranft U, et al. Traffic-related air pollution and incident type 2 diabetes: results from the SALIA cohort study. Environ Health Perspect. 2010 Sep;118(9):1273–9.
World Health Organization. WHO Air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide. Global update 2005. Summary of risk assessment [Internet]. Geneva: WHO; 2006 [2017 May14]. Available from: http://whqlibdoc.who.int/hq/2006/WHO_SDE_PHE_OEH_06.02_eng.pdf?ua=1.
World Health Organization. Media centre. Ambient (outdoor) air quality and health. Fact sheet. Geneva: WHO [2017 Apr 14]. Available from: http://www.who.int/mediacentre/factsheets/fs313/en/.
Evropska Agencija za Okolje. Kakovost zraka v zaprtih prostorih, 2016[2017 May 4]. Available from: http://www.eea.europa.eu/sl/eea-signali/signali-2013/clanki/kakovost-zraka-v-zaprtih-prostorih.
Mazzoli-Rocha F, Fernandes S, Einicker-Lamas M, Zin WA. Roles of oxidative stress in signaling and inflammation induced by particulate matter. Cell Biol Toxicol. 2010 Oct;26(5):481–98.
Nemmar A, Hoet PH, Vanquickenborne B, Dinsdale D, Thomeer M, Hoylaerts MF, et al. Passage of inhaled particles into the blood circulation in humans. Circulation. 2002 Jan;105(4):411–4.
Chuang GC, Yang Z, Westbrook DG, Pompilius M, Ballinger CA, White CR, et al. Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L209–16.
Wang XB, Jin HF, Tang CS, Du JB. The biological effect of endogenous sulfur dioxide in the cardiovascular system. Eur J Pharmacol. 2011 Nov;670(1):1–6.
Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, et al. American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation. 2010 Jun;121(21):2331–78.
Dutta A, Ray MR, Banerjee A. Systemic inflammatory changes and increased oxidative stress in rural Indian women cooking with biomass fuels. Toxicol Appl Pharmacol. 2012 Jun;261(3):255–62.
Ghio AJ, Devlin RB. Inflammatory lung injury after bronchial instillation of air pollution particles. Am J Respir Crit Care Med. 2001 Aug;164(4):704–8.
Donaldson K, Stone V, Borm PJ, Jimenez LA, Gilmour PS, Schins RP, et al. Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10). Free Radic Biol Med. 2003 Jun;34(11):1369–82.
WHO. Air quality guidelines global update 2005. Particulate metter, ozone, nitrogen dioxid and sulfur dioxide. Denmark: World Health Organisation Regional Office for Evrope, 2006 [2015 Apr 6]. Available from: http://www.who.int/phe/health_topics/outdoorair/outdoorair_aqg/en/.
Bruce N, Perez-Padilla R, Albalak R. The health effects of indoor air pollution exposure in developing countries. Geneva. World Health organisation; 2002. pg. 11.
Grigg J. Effect of biomass smoke on pulmonary host defence mechanisms. Paediatr Respir Rev. 2007 Dec;8(4):287–91.
Nemmar A, Vanbilloen H, Hoylaerts MF, Hoet PH, Verbruggen A, Nemery B. Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. Am J Respir Crit Care Med. 2001 Nov;164(9):1665–8.
Liu L, Poon R, Chen L, Frescura AM, Montuschi P, Ciabattoni G, et al. Acute effects of air pollution on pulmonary function, airway inflammation, and oxidative stress in asthmatic children. Environ Health Perspect. 2009 Apr;117(4):668–74.
Perzanowski MS, Chew GL, Divjan A, Jung KH, Ridder R, Tang D, et al. Early-life cockroach allergen and polycyclic aromatic hydrocarbon exposures predict cockroach sensitization among inner-city children. J Allergy Clin Immunol. 2013 Mar;131(3):886–93.
Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014 Mar;20(7):1126–67.
Patel MM, Chillrud SN, Deepti KC, Ross JM, Kinney PL. Traffic-related air pollutants and exhaled markers of airway inflammation and oxidative stress in New York City adolescents. Environ Res. 2013 Feb;121:71–8.
Diaz-Sanchez D, Tsien A, Fleming J, Saxon A. Combined diesel exhaust particulate and ragweed allergen challenge markedly enhances human in vivo nasal ragweed-specific IgE and skews cytokine production to a T helper cell 2-type pattern. J Immunol. 1997 Mar;158(5):2406–13.
Diaz-Sanchez D. The role of diesel exhaust particles and their associated polyaromatic hydrocarbons in the induction of allergic airway disease. Allergy. 1997;52(38 Suppl):52–6.
Diaz-Sanchez D, Penichet-Garcia M, Saxon A. Diesel exhaust particles directly induce activated mast cells to degranulate and increase histamine levels and symptom severity. J Allergy Clin Immunol. 2000 Dec;106(6):1140–6.
van Zijverden M, Granum B. Adjuvant activity of particulate pollutants in different mouse models. Toxicology. 2000 Nov;152(1–3):69–77.
Taylor A, Verhagen J, Akdis CA, Akdis M. T regulatory cells and allergy. Microbes Infect. 2005 Jun;7(7–8):1049–55.
Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, et al. Ambient air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol. 2010 Oct;126(4):845–852.e10.
Koppelman GH, Nawijn MC. Recent advances in the epigenetics and genomics of asthma. Curr Opin Allergy Clin Immunol. 2011 Oct;11(5):414–9.
Holloway JW, Savarimuthu Francis S, Fong KM, Yang IA. Genomics and the respiratory effects of air pollution exposure. Respirology. 2012 May;17(4):590–600.
Carlsten C, Melén E. Air pollution, genetics, and allergy: an update. Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):455–60.
Erridge C. Endogenous ligands of TLR2 and TLR4: agonists or assistants? J Leukoc Biol. 2010 Jun;87(6):989–99.
Becker S, Dailey L, Soukup JM, Silbajoris R, Devlin RB. TLR-2 is involved in airway epithelial cell response to air pollution particles. Toxicol Appl Pharmacol. 2005 Feb;203(1):45–52.
Becker S, Fenton MJ, Soukup JM. Involvement of microbial components and toll-like receptors 2 and 4 in cytokine responses to air pollution particles. Am J Respir Cell Mol Biol. 2002 Nov;27(5):611–8.
Auerbach A, Hernandez ML. The effect of environmental oxidative stress on airway inflammation. Curr Opin Allergy Clin Immunol. 2012 Apr;12(2):133–9.
Hollingsworth JW, Maruoka S, Li Z, Potts EN, Brass DM, Garantziotis S, et al. Ambient ozone primes pulmonary innate immunity in mice. J Immunol. 2007 Oct;179(7):4367–75.
Williams AS, Leung SY, Nath P, Khorasani NM, Bhavsar P, Issa R, et al. Role of TLR2, TLR4, and MyD88 in murine ozone-induced airway hyperresponsiveness and neutrophilia. J Appl Physiol (1985). 2007 Oct;103(4):1189–95.
Kerkhof M, Postma DS, Brunekreef B, Reijmerink NE, Wijga AH, de Jongste JC, et al. Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma. Thorax. 2010 Aug;65(8):690–7.
Boland S, Baeza-Squiban A, Fournier T, Houcine O, Gendron MC, Chévrier M, et al. Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production. Am J Physiol. 1999 Apr;276(4 Pt 1):L604–13.
Fujii T, Hayashi S, Hogg JC, Mukae H, Suwa T, Goto Y, et al. Interaction of alveolar macrophages and airway epithelial cells following exposure to particulate matter produces mediators that stimulate the bone marrow. Am J Respir Cell Mol Biol. 2002 Jul;27(1):34–41.
Becher R, Bucht A, Øvrevik J, Hongslo JK, Dahlman HJ, Samuelsen JT, et al. Involvement of NADPH oxidase and iNOS in rodent pulmonary cytokine responses to urban air and mineral particles. Inhal Toxicol. 2007 Jun;19(8):645–55.
Quay JL, Reed W, Samet J, Devlin RB. Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-kappaB activation. Am J Respir Cell Mol Biol. 1998 Jul;19(1):98–106.
Shukla A, Timblin C, BeruBe K, Gordon T, McKinney W, Driscoll K, et al. Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. Am J Respir Cell Mol Biol. 2000 Aug;23(2):182–7.
Tamagawa E, Bai N, Morimoto K, Gray C, Mui T, Yatera K, et al. Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction. American Journal of Physiology. 2008 Jul;295(1):L79-85.
Törnqvist H, Mills NL, Gonzalez M, Miller MR, Robinson SD, Megson IL, et al. Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am J Respir Crit Care Med. 2007 Aug;176(4):395–400.
Van Eden SF, Tan WC, Suwa T, Mukae H, Terashima T, Fujii T, et al. et al. Cytokines involved in systematic inflammatory response induced by exposure to particulat matter air pollutants (PM (10)). A. J Respir. Crit Care Med. 2001;164(5):826–30.
Gong H Jr, Linn WS, Terrell SL, Anderson KR, Clark KW, Sioutas C, et al. Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution. Inhal Toxicol. 2004 Oct-Nov;16(11–12):731–44.
Ghio AJ, Hall A, Bassett MA, Cascio WE, Devlin RB. Exposure to concentrated ambient air particles alters hematologic indices in humans. Inhal Toxicol. 2003 Dec;15(14):1465–78.
Frampton MW, Stewart JC, Oberdörster G, Morrow PE, Chalupa D, Pietropaoli AP, et al. Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. Environ Health Perspect. 2006 Jan;114(1):51–8.
Gold DR, Mittleman MA. New insights into pollution and the cardiovascular system: 2010 to 2012. Circulation. 2013 May;127(18):1903–13.
Peters A, Veronesi B, Calderón-Garcidueñas L, Gehr P, Chen LC, Geiser M, et al. Translocation and potential neurological effects of fine and ultrafine particles a critical update. Part Fibre Toxicol. 2006 Sep;3(1):13.
L Hou, Zhu Z Z, Zhang X, Nordio F, Bonzini M, Schwartz J, et al. Airborne particulate matter and mitochondrial damage: a cross-sectional study. Environmental Health A. 2010;9: article 48.
Higgins GC, Beart PM, Shin YS, Chen MJ, Cheung NS, Nagley P. Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury. J Alzheimers Dis. 2010;20(20 Suppl 2):S453–73.
Orrenius S, Nicotera P, Zhivotovsky B. Cell death mechanisms and their implications in toxicology. Toxicol Sci. 2011 Jan;119(1):3–19.
Martinon F, Glimcher LH. Regulation of innate immunity by signaling pathways emerging from the endoplasmic reticulum. Curr Opin Immunol. 2011 Feb;23(1):35–40.
Laing S, Wang G, Briazova T, Zhang C, Wang A, Zheng Z, et al. Airborna particulatze matter selectively activates endoplasmatic reticulum stress response in the lung and liver tissue. Am J Physiol. 2010;4(299):736–49.
Watterson TL, Hamilton B, Martin R, Coulombe RA Jr. Urban particulate matter causes ER stress and the unfolded protein response in human lung cells. Toxicol Sci. 2009 Nov;112(1):111–22.
Jung EJ, Avliyakulov NK, Boontheung P, Loo JA, Nel AE. Pro-oxidative DEP chemicals induce heat shock proteins and an unfolding protein response in a bronchial epithelial cell line as determined by DIGE analysis. Proteomics. 2007 Nov;7(21):3906–18.
WHO. Systemic review of air pollution, a glaobal update. 2006.
Pope CA 3rd, Dockery DW. Health effects of fine particulate air pollution: lines that connect. J Air Waste Manag Assoc. 2006 Jun;56(6):709–42.
Brunekreef B, Holgate ST. Air pollution and health. Lancet. 2002 Oct;360(9341):1233–42.
Cunningham C, Campion S, Lunnon K, Murray CL, Woods JF, Deacon RM, et al. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry. 2009 Feb;65(4):304–12.
Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 Jan;9(1):46–56.
Lagrish J P, Unosson J, Bosson J, Barath S, Muala A, Blackwell S, et al. Altered nitriic oxide bioavailability contributes to disel exhaust inhalation-induced cardiovascular dysfunction in man. J Am Heart Assoc. 2013;2: e004309.
Lucking AJ, Lundbäck M, Barath SL, Mills NL, Sidhu MK, Langrish JP, et al. Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men. Circulation. 2011 Apr;123(16):1721–8.
Brook RD, Bard RL, Morishita M, Dvonch JT, Wang L, Yang HY, et al. Hemodynamic, autonomic, and vascular effects of exposure to coarse particulate matter air pollution from a rural location. Environ Health Perspect. 2014 Jun;122(6):624–30.
Painschab MS, Davila-Roman VG, Gilman RH, Vasquez-Villar AD, Pollard SL, Wise RA, et al. CRONICAS Cohort Study Group. Chronic exposure to biomass fuel is associated with increased carotid artery intima-media thickness and a higher prevalence of atherosclerotic plaque. Heart. 2013 Jul;99(14):984–91.
Schwartz J, Alexeeff SE, Mordukhovich I, Gryparis A, Vokonas P, Suh H, et al. Association between long-term exposure to traffic particles and blood pressure in the Veterans Administration Normative Aging Study. Occup Environ Med. 2012 Jun;69(6):422–7.
Chen H, Burnett RT, Kwong JC, Villeneuve PJ, Goldberg MS, Brook RD, et al. Spatial association between ambient fine particulate matter and incident hypertension. Circulation. 2014 Feb;129(5):562–9.
Fuks KB, Weinmayr G, Foraster M, Dratva J, Hampel R, Houthuijs D, et al. Arterial blood pressure and long-term exposure to traffic-related air pollution: an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Environ Health Perspect. 2014 Sep;122(9):896–905.
Tsai DH, Riediker M, Wuerzner G, Maillard M, Marques-Vidal P, Paccaud F, et al. Short-term increase in particulate matter blunts nocturnal blood pressure dipping and daytime urinary sodium excretion. Hypertension. 2012 Oct;60(4):1061–9.
Jacobs L, Emmerechts J, Hoylaerts MF, Mathieu C, Hoet PH, Nemery B, et al. Traffic air pollution and oxidized LDL. PLoS One. 2011 Jan;6(1):e16200.
Franchini M, Mannucci PM. Thrombogenicity and cardiovascular effects of ambient air pollution. Blood. 2011 Sep;118(9):2405–12.
Kilinç E, Schulz H, Kuiper GJ, Spronk HM, Ten Cate H, Upadhyay S, et al. The procoagulant effects of fine particulate matter in vivo. Part Fibre Toxicol. 2011 Mar;8(1):12.
Tarantini L, Bonzini M, Tripodi A, Angelici L, Nordio F, Cantone L, et al. Blood hypomethylation of inflammatory genes mediates the effects of metal-rich airborne pollutants on blood coagulation. Occup Environ Med. 2013 Jun;70(6):418–25.
Pieters N, Plusquin M, Cox B, Kicinski M, Vangronsveld J, Nawrot TS. An epidemiological appraisal of the association between heart rate variability and particulate air pollution: a meta-analysis. Heart. 2012 Aug;98(15):1127–35.
Marchini T, Magnani N, D’Annunzio V, Tasat D, Gelpi RJ, Alvarez S, et al. Impaired cardiac mitochondrial function and contractile reserve following an acute exposure to environmental particulate matter. Biochim Biophys Acta. 2013 Mar;1830(3):2545–52.
Elbaz A, Moisan F. Update in the epidemiology of Parkinson’s disease. Curr Opin Neurol. 2008 Aug;21(4):454–60.
Lauer K. Environmental risk factors in multiple sclerosis. Expert Rev Neurother. 2010 Mar;10(3):421–40.
Mateen FJ, Brook RD. Air pollution as an emerging global risk factor for stroke. JAMA. 2011 Mar;305(12):1240–1.
MohanKumar SM, Campbell A, Block M, Veronesi B. Particulate matter, oxidative stress and neurotoxicity. Neurotoxicology. 2008 May;29(3):479–88.
Chakraborty S, Kaushik DK, Gupta M, Basu A. Inflammasome signaling at the heart of central nervous system pathology. J Neurosci Res. 2010 Jun;88(8):1615–31.
Bauernfeind F, Ablasser A, Bartok E, Kim S, Schmid-Burgk J, Cavlar T, et al. Inflammasomes: current understanding and open questions. Cell Mol Life Sci. 2011 Mar;68(5):765–83.
Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nat Immunol. 2008 Aug;9(8):857–65.
Trendelenburg G. Acute neurodegeneration and the inflammasome: central processor for danger signals and the inflammation response. 2008; (28)5:867–881. https://doi.org/10.1038/sj.jcbfm.9600609.
Teeling JL, Perry VH. Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: underlying mechanisms. Neuroscience. 2009 Feb;158(3):1062–73.
Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009 Jun;9(6):418–28.
Calderón-Garcidueñas L, Solt AC, Henríquez-Roldán C, Torres-Jardón R, Nuse B, Herritt L, et al. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid β-42 and α-synuclein in children and young adults. Toxicol Pathol. 2008 Feb;36(2):289–310.
Calderón-Garcidueñas L, Mora-Tiscareño A, Ontiveros E, Gómez-Garza G, Barragán-Mejía G, Broadway J, et al. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cogn. 2008 Nov;68(2):117–27.
Møller P, Jacobsen NR, Folkmann JK, Danielsen PH, Mikkelsen L, Hemmingsen JG, et al. Role of oxidative damage in toxicity of particulates. Free Radic Res. 2010 Jan;44(1):1–46.
Møller P, Loft S. Oxidative damage to DNA and lipids as biomarkers of exposure to air pollution. Environ Health Perspect. 2010 Aug;118(8):1126–36.
Migliore L, Coppedè F. Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat Res. 2009 Mar;674(1–2):73–84.
Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 2010 Dec;345(1–2):91–104.
Fernández-Checa JC, Fernández A, Morales A, Marí M, García-Ruiz C, Colell A. Oxidative stress and altered mitochondrial function in neurodegenerative diseases: lessons from mouse models. CNS Neurol Disord Drug Targets. 2010 Aug;9(4):439–54.
Geiser M, Rothen-Rutishauser B, Kapp N, Schürch S, Kreyling W, Schulz H, et al. Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect. 2005 Nov;113(11):1555–60.
Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the nanolevel. Science. 2006 Feb;311(5761):622–7.
Colvin VL, Kulinowski KM. Nanoparticles as catalysts for protein fibrillation. Proc Natl Acad Sci USA. 2007 May;104(21):8679–80.
Linse S, Cabaleiro-Lago C, Xue WF, Lynch I, Lindman S, Thulin E, et al. Nucleation of protein fibrillation by nanoparticles. Proc Natl Acad Sci USA. 2007 May;104(21):8691–6.
Cuervo AM, Wong ES, Martinez-Vicente M. Protein degradation, aggregation, and misfolding. Mov Disord. 2010;25(25 Suppl 1):S49–54.
Nakamura T, Lipton SA. Cell death: protein misfolding and neurodegenerative diseases. Apoptosis. 2009 Apr;14(4):455–68.
Sisó S, Jeffrey M, González L. Sensory circumventricular organs in health and disease. Acta Neuropathol. 2010 Dec;120(6):689–705.
Lewis J, Bench G, Myers O, Tinner B, Staines W, Barr E, et al. Trigeminal uptake and clearance of inhaled manganese chloride in rats and mice. Neurotoxicology. 2005 Jan;26(1):113–23.
Wang J, Liu Y, Jiao F, Lao F, Li W, Gu Y, et al. Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO(2) nanoparticles. Toxicology. 2008 Dec;254(1–2):82–90.
Wang B, Feng WY, Wang M, Shi JW, Zhang F, Ouyang H, et al. Transport of intranasally instilled fine Fe2O3 particles into the brain: micro-distribution, chemical states, and histopathological observation. Biol Trace Elem Res. 2007 Sep;118(3):233–43.
Illum L. Is nose-to-brain transport of drugs in man a reality? J Pharm Pharmacol. 2004 Jan;56(1):3–17.
Oberdörster G, Elder A, Rinderknecht A. Nanoparticles and the brain: cause for concern? J Nanosci Nanotechnol. 2009 Aug;9(8):4996–5007.
Gackière F, Saliba L, Baude A, Bosler O, Strube C. Ozone inhalation activates stress-responsive regions of the CNS. J Neurochem. 2011 Jun;117(6):961–72.
Sun Q, Yue P, Deiuliis JA, Lumeng CN, Kampfrath T, Mikolaj MB, et al. Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation. 2009 Feb;119(4):538–46.
Xu X, Liu C, Xu Z, Tzan K, Zhong M, Wang A, et al. Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue. Toxicol Sci. 2011 Nov;124(1):88–98.
CD-Creative Diagnostic [2017 May 14]. Available from:http://www.creative-diagnostics.com/PI3K-AKT-Signaling-Pathway.htm.
Yan YH, Chou CC, Lee CT, Liu JY, Cheng TJ. Enhanced insulin resistance in diet-induced obese rats exposed to fine particles by instillation. Inhal Toxicol. 2011 Aug;23(9):507–19.
Xu X, Yavar Z, Verdin M, Ying Z, Mihai G, Kampfrath T, et al. Effect of early particulate air pollution exposure on obesity in mice: role of p47phox. Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2518–27.
Turner RC, Holman RR, Matthews D, Hockaday TD, Peto J. Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabolism. 1979 Nov;28(11):1086–96.
Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011 Nov;334(6059):1081–6.
Laing S, Wang G, Briazova T, Zhang C, Wang A, Zheng Z, et al. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues. Am J Physiol Cell Physiol. 2010 Oct;299(4):C736–49.
Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science. 2005 Jan;307(5708):384–7.
Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006 Nov;116(11):3015–25.
Li Z, Potts-Kant EN, Garantziotis S, Foster WM, Hollingsworth JW. Hyaluronan signaling during ozone-induced lung injury requiers TLR4, MyD88, and TIRAP. PLoS One. 2011;6(11):27137.
Sun L, Yu Z, Ye X, Zou S, Li H, Yu D, et al. A marker of endotoxemia is associated with obesity and related metabolic disorders in apparently healthy Chinese. Diabetes Care. 2010 Sep;33(9):1925–32.
Lepper PM, Schumann C, Triantafilou K, Rasche FM, Schuster T, Frank H, et al. Association of lipopolysaccharide-binding protein and coronary artery disease in men. J Am Coll Cardiol. 2007 Jul;50(1):25–31.
Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012 Jan;122(1):153–62.
Purkayastha S, Zhang H, Zhang G, Ahmed Z, Wang Y, Cai D. Neural dysregulation of peripheral insulin action and blood pressure by brain endoplasmic reticulum stress. Proc Natl Acad Sci USA. 2011 Feb;108(7):2939–44.
Nakane H. Translocation of particles deposited in the respiratory system: a systematic review and statistical analysis. Environ Health Prev Med. 2012 Jul;17(4):263–74.
Olofsson PS, Rosas-Ballina M, Levine YA, Tracey KJ. Rethinking inflammation: neural circuits in the regulation of immunity. Immunol Rev. 2012 Jul;248(1):188–204.
Fonken LK, Xu X, Weil ZM, Chen G, Sun Q, Rajagopalan S, et al. Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology. Mol Psychiatry. 2011 Oct;16(10):987–95.
Künzli N, Rapp R, Perez L. Breathe Clean Air: the role of physicians and healthcare proffesionals. Breathe (Sheff). 2014;10(4):2015–9.
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