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Title: Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators

Abstract

Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5–200 μM). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO{sub 3} 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO{sub 3}. We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O{sub 2}{sup −}). At high doses it provokes the secretion of TNFα and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O{submore » 2}{sup −} may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O{sub 2}{sup −} may be blocked, prevailing damage to DNA by the TNFα route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium‐related diseases. -- Highlights: ► Uranyl nitrate effect on cultured macrophages is linked to the doses and independent of its solubility. ► At low doses uranyl nitrate induces generation of superoxide anion. ► At high doses uranyl nitrate provokes secretion of TNFα. ► Uranyl nitrate induces apoptosis through all the range of doses tested.« less

Authors:
 [1];  [1];  [2]
  1. School of Science and Technology, National University of General Martín, Avda Gral Paz 5445 (1650) San Martín, Buenos Aires (Argentina)
  2. (1122), Buenos Aires (Argentina)
Publication Date:
OSTI Identifier:
22215341
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 261; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; ANIONS; APOPTOSIS; DEPLETED URANIUM; DNA; DNA DAMAGES; DOSES; HEALTH HAZARDS; INFLAMMATION; INHALATION; MACROPHAGES; METABOLISM; NEOPLASMS; NUCLEAR FUELS; PHAGOCYTOSIS; RATS; SODIUM CARBONATES; SODIUM CHLORIDES; URANYL NITRATES

Citation Formats

Orona, N.S., Tasat, D.R., E-mail: deborah.tasat@unsam.edu.ar, and School of Dentistry, University of Buenos Aires, M. T. de Alvear 2142. Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.04.022.
Orona, N.S., Tasat, D.R., E-mail: deborah.tasat@unsam.edu.ar, & School of Dentistry, University of Buenos Aires, M. T. de Alvear 2142. Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators. United States. doi:10.1016/J.TAAP.2012.04.022.
Orona, N.S., Tasat, D.R., E-mail: deborah.tasat@unsam.edu.ar, and School of Dentistry, University of Buenos Aires, M. T. de Alvear 2142. Fri . "Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators". United States. doi:10.1016/J.TAAP.2012.04.022.
@article{osti_22215341,
title = {Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators},
author = {Orona, N.S. and Tasat, D.R., E-mail: deborah.tasat@unsam.edu.ar and School of Dentistry, University of Buenos Aires, M. T. de Alvear 2142},
abstractNote = {Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5–200 μM). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO{sub 3} 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO{sub 3}. We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O{sub 2}{sup −}). At high doses it provokes the secretion of TNFα and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O{sub 2}{sup −} may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O{sub 2}{sup −} may be blocked, prevailing damage to DNA by the TNFα route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium‐related diseases. -- Highlights: ► Uranyl nitrate effect on cultured macrophages is linked to the doses and independent of its solubility. ► At low doses uranyl nitrate induces generation of superoxide anion. ► At high doses uranyl nitrate provokes secretion of TNFα. ► Uranyl nitrate induces apoptosis through all the range of doses tested.},
doi = {10.1016/J.TAAP.2012.04.022},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 261,
place = {United States},
year = {2012},
month = {6}
}