Magnetite induces oxidative stress and apoptosis in lung epithelial cells

Ramesh, Vani; Ravichandran, Prabakaran; Copeland, Clinton L.; Gopikrishnan, Ramya; Biradar, Santhoshkumar; Goornavar, Virupaxi; Ramesh, Govindarajan T.; Hall, Joseph

doi:10.1007/s11010-011-1174-x

Cited by 31 publications

(23 citation statements)

References 41 publications

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“…Abundant in all cell compartments, it constitutes the first line of the cellular defense mechanism against oxidative injury [16]. Previous studies demonstrated that ROS generation following GSH depletion caused mitochondrial damage and up-regulation of pro-apoptosis mediators [2,7,18]. We found MgNPs also significantly reduced the GSH level.…”

Section: Resultssupporting

confidence: 52%

“…Among MgNPs, Fe 3 O 4 -containing MgNPs (MgNP-Fe 3 O 4 ; magnetite) are the only MgNPs approved for clinical use. Magnetite has a cubic inverse spinel structure with oxygen forming a face-centered cubic (FCC) closed packing; the interstitial tetrahedral and octahedral sites are occupied by Fe cations [2]. Due to their unique physical, chemical, and mechanical features, MgNPs-Fe 3 O 4 have been used as magnetic resonance imaging contrast agents, targeted drug delivery systems, and hyperthermic agents when placed in an external magnetic field [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Fe3O4 Magnetic Nanoparticles on A549 Cells

Watanabe

Yoneda

Morohashi

et al. 2013

IJMS

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Fe3O4 magnetic nanoparticles (MgNPs-Fe3O4) are widely used in medical applications, including magnetic resonance imaging, drug delivery, and in hyperthermia. However, the same properties that aid their utility in the clinic may potentially induce toxicity. Therefore, the purpose of this study was to investigate the cytotoxicity and genotoxicity of MgNPs-Fe3O4 in A549 human lung epithelial cells. MgNPs-Fe3O4 caused cell membrane damage, as assessed by the release of lactate dehydrogenase (LDH), only at a high concentration (100 μg/mL); a lower concentration (10 μg/mL) increased the production of reactive oxygen species, increased oxidative damage to DNA, and decreased the level of reduced glutathione. MgNPs-Fe3O4 caused a dose-dependent increase in the CD44+ fraction of A549 cells. MgNPs-Fe3O4 induced the expression of heme oxygenase-1 at a concentration of 1 μg/mL, and in a dose-dependent manner. Despite these effects, MgNPs-Fe3O4 had minimal effect on cell viability and elicited only a small increase in the number of cells undergoing apoptosis. Together, these data suggest that MgNPs-Fe3O4 exert little or no cytotoxicity until a high exposure level (100 μg/mL) is reached. This dissociation between elevated indices of cell damage and a small effect on cell viability warrants further study.

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Section: Resultssupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Effects of Fe3O4 Magnetic Nanoparticles on A549 Cells

Watanabe

Yoneda

Morohashi

et al. 2013

IJMS

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“…In detail, 24 hours after Saos-2 cells were plated, 4 different concentrations of FeHA and HA nanoparticles, in a range from 200 μg/ml up to 2000 μg/ml, were added to the culture medium. It should be noted that the concentrations used in this study were significantly higher than the normal concentration used in several nanoparticles studies, in fact even the lowest concentration (200 μg/ml) is in many cases nearly the highest concentration adopted by several groups [21,27,28]. In this regard, the aim of this study was to verify any toxic effects induced by the FeHA MNPs compared to the HA nanoparticles, keeping in mind future in vivo applications, where high nanoparticle accumulation in the cells could influence cell behaviour.…”

Section: Resultsmentioning

confidence: 88%

Intrinsically superparamagnetic Fe-hydroxyapatite nanoparticles positively influence osteoblast-like cell behaviour

et al. 2012

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BackgroundSuperparamagnetic nanoparticles (MNPs) have been progressively explored for their potential in biomedical applications and in particular as a contrast agent for diagnostic imaging, for magnetic drug delivery and more recently for tissue engineering applications. Considering the importance of having safe MNPs for such applications, and the essential role of iron in bone remodelling, this study developed and analysed novel biocompatible and bioreabsorbable superparamagnetic nanoparticles, that avoid the use of poorly tolerated magnetite based nanoparticles, for bone tissue engineering applications.ResultsMNPs were obtained by doping hydroxyapatite (HA) with Fe ions, by directly substituting Fe2+ and Fe3+ into the HA structure yielding superparamagnetic bioactive phase. In the current study, we have investigated the effects of increasing concentrations (2000 μg/ml; 1000 μg/ml; 500 μg/ml; 200 μg/ml) of FeHA MNPs in vitro using Saos-2 human osteoblast-like cells cultured for 1, 3 and 7 days with and without the exposure to a static magnetic field of 320 mT. Results demonstrated not only a comparable osteoblast viability and morphology, but increased in cell proliferation, when compared to a commercially available Ha nanoparticles, even with the highest dose used. Furthermore, FeHA MNPs exposure to the static magnetic field resulted in a significant increase in cell proliferation throughout the experimental period, and higher osteoblast activity.In vivo preliminary results demonstrated good biocompatibility of FeHA superparamagnetic material four weeks after implantation into a critical size lesion of the rabbit condyle.ConclusionsThe results of the current study suggest that these novel FeHA MNPs may be particularly relevant for strategies of bone tissue regeneration and open new perspectives for the application of a static magnetic field in a clinical setting of bone replacement, either for diagnostic imaging or magnetic drug delivery.

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“…Foreign particles, infectious agents and chemicals can induce an inflammatory response in the lung leading to oxidative stress. Also with regard to magnetite, exposure to it has been shown to induce oxidative stress and deplete antioxidant levels in the lung epithelial cells, stimulating the apoptotic pathway for cell death 14 . Furthermore, magnetite particles have been revealed to induce concentration-dependent DNA damage and enhance reactive oxygen species production 6 and micronuclei induction 28 .…”

Section: Discussionmentioning

confidence: 99%

“…Iron is a transition metal that is considered to play a pivotal role in modulating oxidative stress and other biological responses 13 , 14 , which are speculated to be the critical mechanisms in eliciting the adverse effects of iron particulate matter exposure. The Organization for Economic Cooperation and Development (OECD) has generated a list of 14 commercially important nanoparticulate materials, in order to explore the possible health effects and regulate occupational and nonoccupational exposure scenarios, and iron oxide is included in the list 15 .…”

Section: Introductionmentioning

confidence: 99%

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe<sub>3</sub>O<sub>4</sub>) Nanoparticles for 52 Weeks in Fischer 344 Rats

et al. 2013

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Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233–239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes

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Magnetite induces oxidative stress and apoptosis in lung epithelial cells

Cited by 31 publications

References 41 publications

Effects of Fe3O4 Magnetic Nanoparticles on A549 Cells

Effects of Fe3O4 Magnetic Nanoparticles on A549 Cells

Intrinsically superparamagnetic Fe-hydroxyapatite nanoparticles positively influence osteoblast-like cell behaviour

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe<sub>3</sub>O<sub>4</sub>) Nanoparticles for 52 Weeks in Fischer 344 Rats

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