Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

doi:10.1007/s11051-015-3249-1

Cited by 58 publications

(92 citation statements)

References 30 publications

(43 reference statements)

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“…Relevant to this finding, a significant increase of WBCs, neutrophils, lymphocytes, and monocytes in hematology tests was observed in the same groups. Several cases of granulomatous inflammation in the lung were reported in recent toxicity studies using CeO 2 nanoparticles (Toya et al, ; Srinivas et al, ; Aalapati et al, ; Keller et al, ; Peng et al, ), and these were caused by oxidative stress (Srinivas et al, ; Peng et al, ; Hong et al, ; Morimoto et al, ). Specifically, Peng et al () reported that a single intratracheal instillation of CeO 2 nanoparticles to mice caused two waves of lung injury: BAL inflammation and cytotoxicity in the early stage and redox‐activity‐evoked lipid peroxidation, as well as proinflammation in the latter stage.…”

Section: Discussionmentioning

confidence: 99%

Twenty‐eight‐day repeated inhalation toxicity study of nano‐sized lanthanum oxide in male sprague‐dawley rats

Shin

Lim

Kim

et al. 2016

Environmental Toxicology

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Although the use of lanthanum has increased in field of high-tech industry worldwide, potential adverse effects to human health and to the environment are largely unknown. The present study aimed to investigate the potential toxicity of nano-sized lanthanum oxide (La O ) following repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed nose-only to nano-sized La O for 28 days (5 days/week) at doses of 0, 0.5, 2.5, and 10 mg/m . In the experimental period, we evaluated treatment-related changes including clinical signs, body weight, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology findings. We also analyzed lanthanum distribution in the major organs and in the blood, bronchoalveolar lavage fluids (BALF), and oxidative stress in lung tissues. Lanthanum level was highest in lung tissues and showed a dose-dependent relation. Alveolar proteinosis was observed in all treatment groups and was accompanied by an increase in lung weight; moreover, lung inflammation was observed in the 2.5 mg/m and higher dose groups and was accompanied by an increase in white blood cells. In the BALF, total cell counts including macrophages and neutrophils, lactate dehydrogenase, albumin, nitric oxide, and tumor necrosis factor-alpha increased significantly in all treatment groups. Furthermore, these changes tended to deteriorate in the 10 mg/m group at the end of the recovery period. In the present experimental conditions, we found that the lowest-observed-adverse-effect level of nano-sized La O was 0.5 mg/m in male rats, and the target organ was the lung. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1226-1240, 2017.

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Section: Discussionmentioning

confidence: 99%

Twenty‐eight‐day repeated inhalation toxicity study of nano‐sized lanthanum oxide in male sprague‐dawley rats

Shin

Lim

Kim

et al. 2016

Environmental Toxicology

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“…instillation or inhalation CeO 2 NPs [15–18, 42]. However, as far as we are aware, no study has investigated systematically the oxidative stress (LPO, ROS, SOD, GSH, and total NO), inflammation (TNF- α , IL-6, and IL-1 β ), and DNA damage in the lung and important secondary organs including heart, liver, kidney, spleen, and brain.…”

Section: Discussionmentioning

confidence: 99%

Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

Nemmar

Yuvaraju

Beegam

et al. 2017

Oxidative Medicine and Cellular Longevity

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CeO2 nanoparticles (CeO2 NPs) which are used as a diesel fuel additive are emitted in the particulate phase in the exhaust, posing a health concern. However, limited information exists regarding the in vivo acute toxicity of CeO2 NPs on multiple organs. Presently, we investigated the acute (24 h) effects of intratracheally instilled CeO2 NPs in mice (0.5 mg/kg) on oxidative stress, inflammation, and DNA damage in major organs including lung, heart, liver, kidneys, spleen, and brain. Lipid peroxidation measured by malondialdehyde production was increased in the lungs only, and reactive oxygen species were increased in the lung, heart, kidney, and brain. Superoxide dismutase activity was decreased in the lung, liver, and kidney, whereas glutathione increased in lung but it decreased in the kidney. Total nitric oxide was increased in the lung and spleen but it decreased in the heart. Tumour necrosis factor-α increased in all organs studied. Interleukin- (IL-) 6 increased in the lung, heart, liver, kidney, and spleen. IL-1β augmented in the lung, heart, kidney, and spleen. Moreover, CeO2 NPs induced DNA damage, assessed by COMET assay, in all organs studied. Collectively, these findings indicate that pulmonary exposure to CeO2 NPs causes oxidative stress, inflammation, and DNA damage in multiple organs.

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“…Inhalation of CeO 2 induced pulmonary inflammation in a concentration-dependent manner with post-exposure persistency [3, 17, 22, 23]. Respective studies further indicated distribution of cerium to extra-pulmonary organs [16, 17, 22] and impaired nanoparticle clearance at high dose levels (≥ 5 mg/m 3 ) [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats

et al. 2017

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BackgroundNanomaterials like cerium oxide and barium sulfate are frequently processed in industrial and consumer products and exposure of humans and other organisms is likely. Generally less information is given on health effects and toxicity, especially regarding long-term exposure to low nanoparticle doses. Since inhalation is still the major route of uptake the present study focused on pulmonary effects of CeO2NM-212 (0.1, 0.3, 1.0, 3.0 mg/m3) and BaSO4NM-220 nanoparticles (50.0 mg/m3) in a 90-day exposure setup. To define particle-related effects and potential mechanisms of action, observations in histopathology, bronchoalveolar lavage and immunohistochemistry were linked to pulmonary deposition and clearance rates. This further allows evaluation of potential overload related effects.ResultsLung burden values increased with increasing nanoparticle dose levels and ongoing exposure. At higher doses, cerium clearance was impaired, suggesting lung overload. Barium elimination was extremely rapid and without any signs of overload. Bronchoalveolar lavage fluid analysis and histopathology revealed lung tissue inflammation with increasing severity and post-exposure persistency for CeO2. Also, marker levels for genotoxicity and cell proliferation were significantly increased. BaSO4 showed less inflammation or persistency of effects and particularly affected the nasal cavity.ConclusionCeO2 nanoparticles penetrate the alveolar space and affect the respiratory tract after inhalation mainly in terms of inflammation. Effects at low dose levels and post-exposure persistency suggest potential long-term effects and a notable relevance for human health. The generated data might be useful to improve nanoparticle risk assessment and threshold value generation. Mechanistic investigations at conditions of non-overload and absent inflammation should be further investigated in future studies.

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Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

Cited by 58 publications

References 30 publications

Twenty‐eight‐day repeated inhalation toxicity study of nano‐sized lanthanum oxide in male sprague‐dawley rats

Twenty‐eight‐day repeated inhalation toxicity study of nano‐sized lanthanum oxide in male sprague‐dawley rats

Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats

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