title: Oxidative-stress potency of organic extracts of diesel exhaust and urban fine particles in rat heart microvessel endothelial cells.
abstract: Exposure to fine particulate materials is associated with an increase in mortality rate of cardiovascular diseases. Particles deposited in the lung may affect the vascular system both directly (leaching of soluble components from particles) and indirectly (via cytokines and mediators). The present study addressed cytotoxicity and oxidative stress potency of organic extracts of diesel exhaust particles (OE-DEP) and urban fine particles (OE-UFP) in rat heart microvessel endothelial (RHMVE) cells. The LC(50) values of OE-DEP and OE-UFP were calculated to be 17 and 34 microg/ml, respectively, suggesting that OE-DEP was more cytotoxic than OE-UFP. The viability of OE-DEP- and OE-UFP-exposed cells was ameliorated by N-acetyl-L-cysteine (NAC). The cell monolayer was exposed to 0 (control), 1, 3, and 10 microg/ml OE-DEP for 6 h and mRNA levels of antioxidant enzymes such as heme oxygenase-1 (HO-1), thioredoxin peroxidase 2 (TRPO), glutathione S-transferase P subunit (GST-P), and NADPH dehydrogenase (NADPHD) were quantitated by northern analysis. All those mRNA levels increased dose-dependently with OE-DEP and HO-1 mRNA showed the most marked response to OE-DEP. mRNA levels of those antioxidant enzymes and heat shock protein 72 (HSP72) in OE-DEP-exposed cells were higher than those of OE-UFP-exposed cells as compared at the same concentration. The transcription levels of HO-1 and HSP72 in OE-DEP- and OE-UFP-exposed cells were also reduced by NAC. Those results suggest that the organic fraction of particulate materials in the urban air has a potency to cause oxidative stress to endothelial cells and may be implicated in cardiovascular diseases through functional changes of endothelial cells.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. seishiro@nies.go.jp
authors.forename: Seishiro
authors.initials: S
authors.lastname: Hirano
authors.forename: Akiko
authors.initials: A
authors.lastname: Furuyama
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005982:Glutathione Transferase / Q000187:drug effects / Q000235:genetics; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000235:genetics; D009206:Myocardium / Q000166:cytology; D009252:NADPH Dehydrogenase / Q000187:drug effects / Q000235:genetics; D009363:Neoplasm Proteins; D018384:Oxidative Stress; D010316:Particle Size; D010544:Peroxidases / Q000187:drug effects / Q000235:genetics; D054464:Peroxiredoxins; D051381:Rats; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D001335:Vehicle Emissions; D010544:Peroxidases; D054464:Peroxiredoxins; D006419:Heme Oxygenase (Decyclizing); D009252:NADPH Dehydrogenase; D005982:Glutathione Transferase; D000111:Acetylcysteine