Please cite this article in press as: S. Manzetti, O. Andersen, Biochemical and physiological effects from exhaust emissions. A review of the relevant literature, Pathophysiology (2016), http://dx.doi.org/10.1016/j.pathophys.2016.10.002 ARTICLE IN PRESS G Model PATPHY-882; No. of Pages 9 Pathophysiology xxx (2016) xxx–xxx Contents lists available at ScienceDirect Pathophysiology jo ur nal ho me page: www.elsevier.com/locate/pathophys Review Biochemical and physiological effects from exhaust emissions. A review of the relevant literature Sergio Manzetti a , Otto Andersen b,* a Fjordforsk AS, Midtun, 6894 Vangsnes, Norway b Vestlandsforskning, Fosshaugane Campus, 6851 Sogndal, Norway a r t i c l e i n f o Article history: Received 27 June 2016 Accepted 20 October 2016 Available online xxx Keywords: Exhaust Emissions Biochemistry Cell responses Molecular biology Disease mechanisms a b s t r a c t Exhaust emissions are to date ranked among the most frequent causes of premature deaths worldwide. The combustion of fuels such as diesel, gasoline, and bio-blends provokes a series of pathophysiological responses in exposed subjects, which are associated with biochemical and immunological triggering. It is critical to understand these mechanisms, which are directly related to the levels of aerosol, liquid and gaseous components in fuel exhaust (e.g. nanoparticles, particulate matter, volatile compounds), so to cast attention on their toxicity and gradually minimize their use. This review reports findings in the recent literature concerning the biochemical and cellular pathways triggered during intoxication by exhaust emissions, and links these findings to pathophysiological responses such as inflammation and vasoconstriction. This study provides critical in vitro and in vivo data for the reduction of emissions in urban centers, with an emphasis on the prevention of exposure of groups such as children, the elderly, and other affected groups, and shows how the exposure to exhaust emissions induces mechanisms of patho- genesis related to cardiopulmonary pathologies and long-term diseases such as asthma, allergies, and cancer. This review summarizes the cellular and physiological responses of humans to exhaust emissions in a comprehensive fashion, and is important for legislative developments in fuel politics. © 2016 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1.1. Cadherin related responses to exhaust emissions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1.2. Cytokines and interleukins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1.3. Glutathione synthesis pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1.4. Reactive oxygen species (ROS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1.5. P450 and ARNT mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1.6. General inflammatory responses to exhaust emissions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1.7. DNA/RNA responses to exhaust emissions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 1. Introduction Exhaust emissions are ranked as one of the prime causes of death worldwide, and are reported to induce strokes, heart arrhythmia, heart infarct, and cardiac arrest [1,2]. The cause of many of these * Corresponding author. E-mail address: oan@vestforsk.no (O. Andersen). conditions is directly related to the properties of the toxic com- ponents of air pollution; for instance, PM 2.5 and PM 10 (particulate matter with diameter less than 2.5 m and 10 m, respectively) have a strong impact on cardiac function [2,3], while ultra-small nanoparticles tend to affect lung function by causing asthma, chronic bronchitis, and pulmonary disorders [4–7]. The effects from emissions of fuel combustion are also closely related to the chemical characteristics of the pollution components, and as these compounds are continuously changing with the development of http://dx.doi.org/10.1016/j.pathophys.2016.10.002 0928-4680/© 2016 Elsevier B.V. All rights reserved.