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Toxicology of Titanium Dioxide (TiO2) Nanoparticles: In vitro and in vivo evaluation of macrophage uptake of TiO2
Author(s) -
Miller Terry J,
Knapton Alan,
Adeyemo Oluwafunke O,
Noory Laila S,
Weaver James L,
Hanig Joseph P,
Honchel Ronald,
Zhang Jun,
Espandiari Parvaneh,
Benedick Matthew F,
Umbreit Thomas H,
TomazicJezic Vesna J,
Sadrieh Nakissa
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a812
Subject(s) - oxidative stress , cytokine , chemistry , viability assay , macrophage , in vivo , phagocytosis , toxicity , neutral red , spleen , pharmacology , in vitro , microbiology and biotechnology , andrology , cytotoxicity , biology , immunology , biochemistry , medicine , organic chemistry
New Hampshire Ave, Silver Spring, MD, 20993 Potential health risks from TiO 2 in sunscreens and medical products remains unknown. Balb/C mice were injected IV with TiO 2 in saline (size 4.7 nm, 5.6 mg /mouse/day for 2 days) and necropsied on days 3 & 5. The mice showed white discoloration of lungs, liver, and spleen, as well as phagocytosis of TiO 2 aggregates by macrophages in these organs by light microscopy. Kidney and brain of treated mice appeared unchanged. To model macrophage response to TiO 2 in vitro, cultured J774 cells were treated with TiO 2 (0.025–6.3 mg/mL) up to 24 hours and examined for viability, oxidative stress, and cytokine production. TiO 2 ‐treated J774 cells showed dose & time dependent loss of viability via MTT assay. Increased ROS production and loss of cell membrane integrity was observed at higher TiO 2 doses and longer exposure times, by fluorescence microscopy. However, antioxidants α‐tocopherol & trolox failed to prevent TiO 2 ‐induced ROS and cell death, suggesting that oxidative stress may not be the predominant mechanism of TiO 2 toxicity. Cytokine analysis of treated cells revealed an increased release of TNF‐α, IL‐1β, IL‐6, and MIP‐2 with increasing dose and time of exposure to TiO 2 . These data suggest that macrophage uptake and accumulation of large amounts of TiO 2 aggregates may result in cytokine release and potential cytotoxicity in cells and tissues responsible for clearance of TiO 2 from circulation.