PMID- 26934053 OWN - NLM STAT- MEDLINE DCOM- 20160718 LR - 20231213 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 3 DP - 2016 TI - A Health Threat to Bystanders Living in the Homes of Smokers: How Smoke Toxins Deposited on Surfaces Can Cause Insulin Resistance. PG - e0149510 LID - 10.1371/journal.pone.0149510 [doi] LID - e0149510 AB - 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. FAU - Adhami, Neema AU - Adhami N AD - Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America. FAU - Starck, Shelley R AU - Starck SR AD - Department of bioshemistry and Byophysics/ Howard Hughes Medical Institute, Universty of California San Francisco, San Francisco, California, United States of America. FAU - Flores, Cristina AU - Flores C AD - Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America. FAU - Martins Green, Manuela AU - Martins Green M AD - Department of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160302 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Air Pollutants) RN - 0 (Antioxidants) RN - 0 (Tobacco Smoke Pollution) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - H4N855PNZ1 (alpha-Tocopherol) SB - IM EIN - PLoS One. 2016;11(4):e0153382. PMID: 27050097 EIN - PLoS One. 2018 Nov 20;13(11):e0208056. PMID: 30458047 ECI - PLoS One. 2023 Aug 3;18(8):e0289810. PMID: 37535546 MH - Air Pollutants/*adverse effects MH - Animals MH - Antioxidants/pharmacology MH - Catalase/pharmacology MH - DNA Damage/drug effects MH - Diabetes Mellitus, Type 2/metabolism MH - Glutathione Peroxidase/metabolism MH - Hydrogen Peroxide/metabolism MH - Insulin Resistance/*physiology MH - Lipid Peroxidation/drug effects MH - Mice MH - Mice, Inbred C57BL MH - Oxidative Stress/drug effects MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Superoxide Dismutase/metabolism MH - Nicotiana/adverse effects MH - Tobacco Smoke Pollution/*adverse effects MH - alpha-Tocopherol/pharmacology PMC - PMC4774920 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2016/03/05 06:00 MHDA- 2016/07/19 06:00 PMCR- 2016/03/02 CRDT- 2016/03/03 06:00 PHST- 2015/06/24 00:00 [received] PHST- 2016/01/31 00:00 [accepted] PHST- 2016/03/03 06:00 [entrez] PHST- 2016/03/05 06:00 [pubmed] PHST- 2016/07/19 06:00 [medline] PHST- 2016/03/02 00:00 [pmc-release] AID - PONE-D-15-27616 [pii] AID - 10.1371/journal.pone.0149510 [doi] PST - epublish SO - PLoS One. 2016 Mar 2;11(3):e0149510. doi: 10.1371/journal.pone.0149510. eCollection 2016.