title: Potent In Vitro Protection Against PM₂.₅-Caused ROS Generation and Vascular Permeability by Long-Term Pretreatment with Ganoderma tsugae.
abstract: Epidemiological studies show increased particulate matter (PM[Formula: see text]) particles in ambient air are correlated with increased myocardial infarctions. Given the close association of capillaries and alveoli, the dysfunction is caused when inhaled PM[Formula: see text] particles come in close proximity to capillary endothelial cells. We previously suggested that the inhalation of PM[Formula: see text] diesel exhaust particles (DEP) induces oxidative stress and upregulates the Nrf2/HO-1 pathway, inducing vascular permeability factor VEGFA secretion, which results in cell-cell adherens junction disruption and PM[Formula: see text] transmigratation into circulation. Here, we minimized the level that PM[Formula: see text] traveled in the bloodstream by pre-supplementing with a traditional Chinese medicine (TCM) Ganoderma tsugae DMSO extract (GTDE) prior to PM[Formula: see text] exposure. Our results show that PM[Formula: see text] caused alterations in enzyme activities and cellular anti-oxidant balance. We found decreased glutathione levels, a reduced cellular redox ratio, increased ROS generation and cytotoxicity in the cellular fractions. The oxidative stress caused DNA damage and apoptosis, likely causing downstream molecular events that trigger vasculature permeabilization and, eventually, cardiovascular disorders. Our results show long-term GTDE treatment increased endogenous glutathione level, while PM[Formula: see text]-reduced glutathione levels and the cellular redox ratio. GTDE was protective against the genotoxic and apoptotic effects initiated by PM[Formula: see text] oxidative stress. Vascular permeability revealed that PM[Formula: see text] only accumulated on the surface of cells after GTDE treatment; no penetration was detected. After two weeks of GTDE treatment, VEGFA secretion was significantly reduced in human umbilical vein endothelial cells (HUVEC) and endothelial cell migration was blocked. Our results suggest GTDE prevents PM[Formula: see text] transmigration into the bloodstream, and the resultant dysfunction, by inhibiting oxidative stress production and endothelial permeability.
authors.affiliation: * Department of Biomedical Engineering.|‡ Department of Bioscience Technology, Chung Yuan Christian University Taoyuan City 32023, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Tseng
authors.affiliation: ‡ Department of Bioscience Technology, Chung Yuan Christian University Taoyuan City 32023, Taiwan.
authors.forename: Meng-Chi
authors.initials: MC
authors.lastname: Chung
authors.affiliation: ‡ Department of Bioscience Technology, Chung Yuan Christian University Taoyuan City 32023, Taiwan.
authors.forename: Jhih-Syuan
authors.initials: JS
authors.lastname: Wang
authors.affiliation: ‡ Department of Bioscience Technology, Chung Yuan Christian University Taoyuan City 32023, Taiwan.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: ‡ Department of Bioscience Technology, Chung Yuan Christian University Taoyuan City 32023, Taiwan.
authors.forename: Jing-Fen
authors.initials: JF
authors.lastname: Chang
authors.affiliation: ‡ Department of Bioscience Technology, Chung Yuan Christian University Taoyuan City 32023, Taiwan.
authors.forename: Chin-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: § Department of Biochemical Science and Technology, National Taiwan University, Da-an District, Taipei 10617, Taiwan.
authors.forename: Ruey-Shyang
authors.initials: RS
authors.lastname: Hseu
authors.affiliation: † Center of Nanotechnology.|‡ Department of Bioscience Technology, Chung Yuan Christian University Taoyuan City 32023, Taiwan.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chao
mesh_terms: D002199:Capillary Permeability / Q000187:drug effects*; D032902:Ganoderma / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D009203:Myocardial Infarction / Q000139:chemically induced; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000009:adverse effects* / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D052638:Particulate Matter; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005978:Glutathione
keywords: Ganoderma tsugae DMSO Extracts; PM; Permeability; ROS; Traditional Chinese Medicine