title: Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing.
abstract: Third hand smoke (THS) is the accumulation of second hand smoke (SHS) toxins on surfaces in homes, cars, clothing and hair of smokers. It is known that 88M US nonsmokers ≥3 years old living in homes of smokers are exposed to THS toxicants and show blood cotinine levels of ≥0.05 ng/ml, indicating that the toxins are circulating in their circulatory systems. The goal of the present study is to investigate the mechanisms by which THS causes impaired wound healing. We show that mice living under conditions that mimic THS exposure in humans display delayed wound closure, impaired collagen deposition, altered inflammatory response, decreased angiogenesis, microvessels with fibrin cuffs and a highly proteolytic wound environment. Moreover, THS-exposed mouse wounds have high levels of oxidative stress and significantly lower levels of antioxidant activity leading to molecular damage, including protein nitration, lipid peroxidation and DNA damage that contribute to tissue dysfunction. Furthermore, we show that elastase is elevated, suggesting that elastin is degraded and the plasticity of the wound tissue is decreased. Taken together, our results lead us to conclude that THS toxicants delay and impair wound healing by disrupting the sequential processes that lead to normal healing. In addition, the lack of elastin results in loss of wound plasticity, which may be responsible for reopening of wounds.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA 92521, U.S.A.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dhall
authors.affiliation: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA 92521, U.S.A.
authors.forename: Raquelle
authors.initials: R
authors.lastname: Alamat
authors.affiliation: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA 92521, U.S.A.
authors.forename: Anthony
authors.initials: A
authors.lastname: Castro
authors.affiliation: Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, U.S.A.
authors.forename: Altaf H
authors.initials: AH
authors.lastname: Sarker
authors.affiliation: Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, U.S.A.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.affiliation: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA 92521, U.S.A.
authors.forename: Alex
authors.initials: A
authors.lastname: Chan
authors.affiliation: Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, U.S.A.
authors.forename: Bo
authors.initials: B
authors.lastname: Hang
authors.affiliation: Department of Cell Biology and Neuroscience, University of California at Riverside, Riverside, CA 92521, U.S.A. manuela.martins@ucr.edu.
authors.forename: Manuela
authors.initials: M
authors.lastname: Martins-Green
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D018925:Chemokines / Q000096:biosynthesis; D003094:Collagen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014945:Wound Healing
chemical_list: D018925:Chemokines; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D014028:Tobacco Smoke Pollution; D003094:Collagen
keywords: DNA damage; angiogenesis; cytokine; inflammation; reactive oxygen species and antioxidants; toxicants