Ultrasmall superparamagnetic iron oxide nanoparticles acutely promote thrombosis and cardiac oxidative stress and DNA damage in mice

Nemmar, Abderrahim; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Tariq, Saeed; Attoub, Samir; Ali, Badreldin H.

doi:10.1186/s12989-016-0132-x

Cited by 98 publications

(63 citation statements)

References 60 publications

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“…Single-cell suspensions of the different lungs, hearts, livers, kidneys, spleens, and brains were obtained and analyzed according to the method described in our previous publications [27–30]. …”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…The degree of platelet aggregation following CeO 2 NP exposure was calculated as a fall in the number of single platelets counted and expressed as a % of control (saline-treated blood). 27 In vitro measurement of prothrombin time (PT) and activated partial thromboplastin time (aPTT) After anesthesia, blood from untreated mice was withdrawn, as described earlier. The PT was measured on freshly collected, platelet-poor plasma with human, relipidated, recombinant thromboplastin (Recombiplastin; Instrumentation Laboratory, Orangeburg, NY, USA) in combination with an MC 1 VET (Merlin).…”

Section: Experimental Pial Cerebral Arteriole Thrombosis Modelmentioning

confidence: 99%

“…27,37,45 In this model, the damage to endothelial cells causes the platelets to adhere at the site of endothelial damage and then aggregate. 27,37,45 The data of the present study show that acute IT administration of CeO 2 NPs induced a significant and dose-dependent shortening of the thrombotic occlusion time in pial arterioles and venules, indicating that CeO 2 NPs possess prothrombotic effects. Along with thrombosis in vivo, a dose-dependent and significant increase in the concentrations of the coagulation factor, fibrinogen, and PAI-1 in the plasma following acute exposure to CeO 2 NPs was found.…”

mentioning

confidence: 99%

The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

Al-Salam¹,

Beegam²,

Yuvaraju³

et al. 2017

IJN

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Cerium oxide nanoparticles (CeO 2 NPs), used as a diesel fuel catalyst, can be emitted into the ambient air, resulting in exposure to humans by inhalation. Recent studies have reported the development of lung toxicity after pulmonary exposure to CeO 2 NPs. However, little is known about the possible thrombotic effects of these NPs. The present study investigated the acute (24 hours) effect of intratracheal (IT) instillation of either CeO 2 NPs (0.1 or 0.5 mg/kg) or saline (control) on pulmonary and systemic inflammation and oxidative stress and thrombosis in mice. CeO 2 NPs induced a significant increase of neutrophils into the bronchoalveolar lavage (BAL) fluid with an elevation of tumor necrosis factor α (TNFα) and a decrease in the activity of the antioxidant catalase. Lung sections of mice exposed to CeO 2 NPs showed a dose-dependent infiltration of inflammatory cells consisting of macrophages and neutrophils. Similarly, the plasma levels of C-reactive protein and TNFα were significantly increased, whereas the activities of catalase and total antioxidant were significantly decreased. Interestingly, CeO 2 NPs significantly and dose dependently induced a shortening of the thrombotic occlusion time in pial arterioles and venules. Moreover, the plasma concentrations of fibrinogen and plasminogen activator inhibitor-1 were significantly elevated by CeO 2 NPs. The direct addition of CeO 2 NPs (1, 5, or 25 μg/mL) to mouse whole blood, collected from the inferior vena cava, in vitro neither caused significant platelet aggregation nor affected prothrombin time or partial thromboplastin time, suggesting that the thrombotic events observed in vivo may have resulted from systemic inflammation and/or oxidative stress induced by CeO 2 NPs. This study concludes that acute pulmonary exposure to CeO 2 NPs induces pulmonary and systemic inflammation and oxidative stress and promotes thrombosis in vivo.

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“…Particle phagocytosis by monocytes induced significant oxidative stress and result in severe endothelial toxicity (118). In mice, intravenous injection of FeO-NP (0.4,2 and 10 μg/kg) caused significant prothrombotic effects in pial arterioles and venules as early as 1-hour post-exposure, along with increased cardiac levels of markers of oxidative stress, including lipid peroxidation, ROS levels and increased superoxide dismutase activity (120). …”

Section: Examples Of Enm Vascular Toxicitymentioning

confidence: 99%

“…The ability to generate highly reactive ROS may also account for the inflammatory and cardiovascular effects caused by FeO-NP (120). Moreover, the release of ions within the plasma has also been linked to severe conditions such as hemochromatosis associated with iron overload.…”

Section: Examples Of Enm Vascular Toxicitymentioning

confidence: 99%

Metal Nanomaterial Toxicity Variations Within the Vascular System

Abukabda

Stapleton

Nurkiewicz

2016

Curr Envir Health Rpt

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Engineered nanomaterials (ENM) are anthropogenic materials with at least one dimension less than 100 nm. Their ubiquitous employment in biomedical and industrial applications in the absence of full toxicological assessments raises significant concerns over their safety on human health. This is a significant concern, especially for metal and metal oxide ENM as they may possess the greatest potential to impair human health. A large body of literature has developed that reflects adverse systemic effects associated with exposure to these materials, but an integrated mechanistic framework for how ENM exposure influences morbidity remains elusive. This may be due in large part to the tremendous diversity of existing ENM and the rate at which novel ENM are produced. In this review, the influence of specific ENM physicochemical characteristics and hemodynamic factors on cardiovascular toxicity are discussed. Additionally, the toxicity of metallic, and metal oxide ENM is presented in the context of the cardiovascular system and its discrete anatomical and functional components. Finally, future directions and understudied topics are presented. While it is clear that the nanotechnology boom has increased our interest in ENM toxicity, it is also evident that the field of cardiovascular nanotoxicology remains in its infancy and continued, expansive research is necessary in order to determine the mechanisms via which ENM exposure contributes to cardiovascular morbidity.

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Ultrasmall superparamagnetic iron oxide nanoparticles acutely promote thrombosis and cardiac oxidative stress and DNA damage in mice

Cited by 98 publications

References 60 publications

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

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

The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

Metal Nanomaterial Toxicity Variations Within the Vascular System

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