title: A Health Threat to Bystanders Living in the Homes of Smokers: How Smoke Toxins Deposited on Surfaces Can Cause Insulin Resistance.
abstract: Thirdhand smoke (THS) is the accumulation of secondhand smoke on environmental surfaces. THS is found on the clothing and hair of smokers as well as on surfaces in homes and cars of smokers. Exposure occurs by ingestion, inhalation and dermal absorption. Children living in homes of smokers are at highest risk because they crawl on the floor, touch parents' clothing/hair and household objects. Using mice exposed to THS under conditions that mimic exposure of humans, we show that THS increases cellular oxidative stress by increasing superoxide dismutase (SOD) activity and hydrogen peroxide (H2O2) levels while reducing the activity of antioxidant enzymes catalase and glutathione peroxidase (GPx) that break down H2O2 into H2O and O2. This results in lipid peroxidation, protein nitrosylation and DNA damage. Consequences of these cell and molecular changes are hyperglycemia and insulinemia. Indeed, we found reduced levels of insulin receptor, PI3K, AKT, all important molecules in insulin signaling and glucose uptake by cells. To determine whether these effects on THS-induced insulin resistance are due to increase in oxidative stress, we treated mice exposed to THS with the antioxidants N-acetyl cysteine (NAC) and alpha-tocopherol (alpha-toc) and showed that the oxidative stress, the molecular damage, and the insulin resistance, were significantly reversed. Conversely, feeding the mice with chow that mimics "western diet", which is known to increase oxidative stress, while exposing the mice to THS, further increased the oxidative stress and aggravated hyperglycemia and insulinemia. In conclusion, THS exposure results in insulin resistance in the form of non-obese type II diabetes (NODII) through oxidative stress. If confirmed in humans, these studies could have a major impact on how people view exposure to environmental tobacco toxins, in particular to children, elderly and workers in environments where tobacco smoke has taken place.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.
authors.forename: Neema
authors.initials: N
authors.lastname: Adhami
authors.affiliation: Department of bioshemistry and Byophysics/ Howard Hughes Medical Institute, Universty of California San Francisco, San Francisco, California, United States of America.
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Starck
authors.affiliation: Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.
authors.forename: Cristina
authors.initials: C
authors.lastname: Flores
authors.affiliation: Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.
authors.forename: Manuela
authors.initials: M
authors.lastname: Martins Green
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D014028:Tobacco Smoke Pollution; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D024502:alpha-Tocopherol