title: Acute respiratory and systemic toxicity of pulmonary exposure to rutile Fe-doped TiO(2) nanorods.
abstract: Nanomaterials are extensively used in medicines, industry and daily life, but little is known about their possible health effects. Titanium dioxide (TiO₂) nonmaterial-based photocatalysis is useful in the complete mineralization of organic pollutants in waste water and air. While the Fe-doping of TiO₂ enhances their photocatalytic activity, their potential pathophysiologic effects are unknown. Here, rutile Fe-doped (9%) pure titanium dioxide (TiO₂) nanorods were prepared and characterized. Subsequently, we assessed the acute (24 h) pulmonary and extrapulmonary effects of intratracheal (i.t.) instillation of these nanorods (1 and 5 mg/kg) in Wistar rats. In the bronchoalveolar lavage, the treatment induced a significant and dose-dependent increase of neutrophils, an increase of interleukin-6 (IL-6, at 5 mg/kg), and caused a dose-dependent-decrease of superoxide dismutase (SOD) activity. The lung sections of rats exposed to rutile Fe-TiO₂ nanorods showed infiltration of inflammatory cells in dose-dependent manner. Similarly, the heart rate, systolic blood pressure, plasma IL-6, and leukocyte and platelet numbers were increased at 5 mg/kg. The plasma SOD and reduced glutathaione activities were dose-dependently decreased after exposure to the nanorods. Histopathologically, the liver showed mild inflammatory cells infiltration of few portal tracts, but the kidneys and heart were unaffected. In plasma, the levels of lactate dehydrogenase and hepatic enzymes, i.e., alanine aminotranferease and aspartate aminotransferase were increased significantly. The in vitro exposure of human lung cancer cells NCI-H460-Luc2 and human hepatoma cells HepG2 to FeTiO₂ (6.25-100 μg/ml) dose-dependently reduced cellular viability. Also, the In vitro direct addition of these nanorods (0.1-1 μg/ml) to untreated rat blood, significantly and dose-dependently induced platelet aggregation. In conclusion, exposure to rutile Fe-TiO₂ promotes pulmonary and systemic inflammation and oxidative stress. It affects the liver, enhances thrombotic potential, heart rate and systolic blood pressure. Moreover, the rutile Fe-TiO₂ elicited direct toxicity on NCI-H460-Luc2 and HepG2 cells.
authors.affiliation: Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates. anemmar@hotmail.com
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Nemmar
authors.forename: Khaled
authors.initials: K
authors.lastname: Melghit
authors.forename: Suhail
authors.initials: S
authors.lastname: Al-Salam
authors.forename: Shaheen
authors.initials: S
authors.lastname: Zia
authors.forename: Subramanian
authors.initials: S
authors.lastname: Dhanasekaran
authors.forename: Samir
authors.initials: S
authors.lastname: Attoub
authors.forename: Issa
authors.initials: I
authors.lastname: Al-Amri
authors.forename: Badreldin H
authors.initials: BH
authors.lastname: Ali
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D007501:Iron / Q000737:chemistry*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D043942:Nanotubes; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D014025:Titanium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
chemical_list: D015850:Interleukin-6; C009495:titanium dioxide; D014025:Titanium; D007501:Iron; D013482:Superoxide Dismutase