1 / 19

Oxidant Mechanisms in Response to Ambient Air Particles Beatriz González-Flecha

Oxidant Mechanisms in Response to Ambient Air Particles Beatriz González-Flecha Department of Environmental Health Harvard School of Public Health Boston, MA, USA. Oxygen toxicity: early evidence. Mice. Mice. Drosophila. Rats. Paramecia. Rats. Paramecia.

knowlesm
Download Presentation

Oxidant Mechanisms in Response to Ambient Air Particles Beatriz González-Flecha

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Oxidant Mechanisms in Response to Ambient Air Particles • Beatriz González-Flecha • Department of Environmental Health • Harvard School of Public Health • Boston, MA, USA

  2. Oxygen toxicity: early evidence Mice Mice Drosophila Rats Paramecia Rats Paramecia

  3. Oxygen poisoning and X-irradiation: A mechanism in common R. Gershman et al. Nature, 1954 First demonstration of the involvement of oxygen free radicals in the mechanism of oxygen toxicity

  4. Oxygen Free Radicals = Reactive Oxygen Species (ROS) e- e- e- e- O2-. H2O2 HO• H2O O2 Superoxide anion Hydrogen peroxide Hydroxyl radical • Produced in association to aerobic • metabolism (1952)(1970’s) • Able to promote cell proliferation and • enzyme induction at sublethal • concentrations (1962)(1990) • Toxic at high concentrations (1954) • (1970’s)

  5. Main sources of ROS in mammalian tissues Intracellular source Species 1. Mitochondrial Respiratory Chain Ubiquinone O2-. NADH dehydrogrenase O2-. 2. Enoplasmic Reticulum NADH-cytochrome reductase O2-. or H2O2 Cytochrome P450 O2-. Cytochrome b5 O2-. 3. Plasma Membrane Lipoxygenase 1O2 Prostaglandin synthase 1O2 NADH oxidase (PMN) O2-. 4. Cytosol a) soluble enzymes and proteins Hemoglobin O2-. Xanthine oxidase O2-. b) small molecules Flavins O2-. or H2O2 Thiols O2-.

  6. Radical Chain Protective mechanisms O 2 SOD 10 -11 M •- O O + H O 2 2 2 2 Catalase 10 -7 M H O O + H O 2 2 2 2 • HO Carotene 10 -13 M 1 O O 2 2 Modified from Chance et al. Physiol. Rev. 59, 527-605 (1979).

  7. Radical Chain Protective mechanisms O 2 SOD Damage to cellular components •- O O + H O 2 2 2 2 Catalase H O O + H O 2 2 2 2 • HO Carotene 1 O O 2 2 Modified from Chance et al. Physiol. Rev. 59, 527-605 (1979).

  8. Pulmonary Responses to Oxygen 20% O2Normoxia 85% O2Adaptive responses: Proliferation of epithelial cells Induction of antioxidant enzymes 100 % O2Damage to the lung epithelium Inflammation Edema Post-100% O2Reparative responses: Epithelial remodeling Enzyme induction

  9. Cellular Responses to ROS ROS concentration

  10. Health Effects of Ambient Air Particles

  11. 1943- Los Angeles, CA Visibility 3 Blocks. Numerous complaints watery eyes, nausea, & respiratory discomfort

  12. 20 People and 1,000's animals dead, 6,000 ill

  13. 1952- London, England 4,000 Dead

  14. Ambient air particles have intrinsic toxicity Particle pollution, and not other pollutants, leads to increased death across much of the USA (HEI:www.healtheffects.org.news)

  15. Particle Sources • Anthropogenic sources • Transportation • Power plants • Incinerators • Wood burning • Natural Sources • Volcanoes • Erosion • Forest fires • Sea spray • Soil • Biological (pollen, spores)

  16. Ambient Air Particles and Oxidants • CAPs increase luminol-enhanced chemiluminescence, and the oxidation of redox-sensitive fluorescent markers in PMN and alveolar macrophages in vitro • Quinone radicals were detected in air particles @ 1010 per mg • PM inhalation induces anti-oxidant enzymes • Oxidants induce expression of pro-inflammatory cytokines

  17. Mechanism of Pulmonary Oxidative Stress and Toxicity by PM • Particle/cell interactions • Direct action on intracellular sources of ROS • Potentiation by macrophage-derived cytokines • TNF-alpha, IL-8, etc.

  18. Cardiac Effects of PM Neural mechanisms sympathetic/parasympathetic stimulation of the heart Inflammatory mechanisms release of cytokine/chemokine into circulation Direct action on the heart Soluble components (inorganic and organic) Insoluble (ultrafine/fine particles)

  19. Summary • The health effects of PM in humans as well as the biological effects of CAPs in animal and cell models are well documented • The existing evidence strongly suggests that ROS are involved in the initiation steps of the mechanistic pathways leading from PM exposure to inflammatory effects and cardiopulmonary toxicity • The cellular mechanisms of PM toxicity are currently under investigation

More Related