Dose-, Treatment- and Time-Dependent Toxicity of Superparamagnetic Iron Oxide Nanoparticles on Primary Rat Hepatocytes

Gokduman, Kurtulus; Bestepe, Furkan; Li, Lei; Yarmush, Martin L.; Usta, O. Berk

doi:10.2217/nnm-2017-0387

Cited by 33 publications

(20 citation statements)

References 82 publications

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“…The exposure of hepatocytes to 50 ppm of P25 and anatase resulted in relatively highest ROS production while exposure to the same concentration of rutile demonstrated lesser ROS production.30TiO 2 Pure rutile50–TiO 2 Pure anatase50–SPION10–Primary rat hepatocytes0–400 μg/mL48 hrsThe LD50 values were calculated as 328.51 ± 18.25 and 319.79 ± 25.73 for one-shot and cumulative treatment styles, respectively. The time-dependent ROS production data from the current study illustrates that ROS can be used as an early and potent diagnostic marker for SPION-induced toxicity as well as other nanotoxicological inquiries in the liver.76Fe 3 O 4 -TiO 2 20–25–HL-7702Ti: 0; 6.25; 15.625 25 µg/cm 2 12 hrsFe 3 O 4 -TiO 2 NPs induced cellular ROS generation, reduced cell viability, and induced apoptosis in a dose-dependent manner in HL7702 cells. Mitochondrial membrane was damaged and cytochrome c was released, followed by regulation of apoptosis-related proteins.96 Abbreviations: HSCs, hepatic stellate cells; MMP, matrix metalloprotein; IC50, half-maximal inhibitory concentration; PVA, Polyvinyl alcohol; GSH, glutathione; NLRP3:NLRs, pyrin domain containing 3; LC50, median lethal concentration; MAPK, mitogen-activated protein kinase; AKT, protein kinase B; CHANG, human Chang liver cells; LD50, median lethal dose; SPION, superparamagnetic iron oxide nanoparticles.…”

Section: The Hepatocytes and Metallic Nanoparticles Toxicitymentioning

confidence: 68%

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The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes

Ying¹,

Zang²,

Qu³

et al. 2019

IJN

142

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Metallic nanoparticles (MNPs) are new engineering materials with broad prospects for biomedical applications; thus, their biosafety has drawn great concern. The liver is the main detoxification organ of vertebrates. However, many issues concerning the interactions between MNPs and biological systems (cells and tissues) are unclear, particularly the toxic effects of MNPs on hepatocytes and other liver cells. Numerous researchers have shown that some MNPs can induce decreased cell survival rate, production of reactive oxygen species (ROS), mitochondrial damage, DNA strand breaks, and even autophagy, pyroptosis, apoptosis, or other forms of cell death. Our review focuses on the recent researches on the liver toxicity of MNPs and its mechanisms at cellular and subcellular levels to provide a scientific basis for the subsequent hepatotoxicity studies of MNPs.

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Section: The Hepatocytes and Metallic Nanoparticles Toxicitymentioning

confidence: 68%

“…In vitro studies, Fe 3 O 4 NPs exposure to primary rat hepatocytes showed that the excessive production of ROS was mainly due to the damage of mitochondria by MNPs 7677.…”

Section: Mechanisms Of Hepatotoxicity Induced By Metallic Nanoparticlesmentioning

confidence: 99%

The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes

Ying¹,

Zang²,

Qu³

et al. 2019

IJN

142

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“…Gokduman et al investigated the dose, treatment, and time-dependent toxicity of superparamagnetic Fe 3 O 4 NPs (10 nm, 0–400 μg/mL) on primary rat hepatocytes. The obtained results suggested that the response of ROS increased with increasing concentrations of Fe 3 O 4 NPs [39,40].…”

Section: Discussionmentioning

confidence: 99%

The Toxicity Assessment of Iron Oxide (Fe3O4) Nanoparticles on Physical and Biochemical Quality of Rainbow Trout Spermatozoon

Özgür

Ulu

Balcıoğlu

et al. 2018

Toxics

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The aim of this study was to evaluate the in vitro effect of different doses (50, 100, 200, 400, and 800 mg/L) of Fe3O4 nanoparticles (NPs) at 4 °C for 24 h on the kinematics of rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) spermatozoon. Firstly, Fe3O4 NPs were prepared at about 30 nm from Iron (III) chloride, Iron (II) chloride, and NH3 via a co-precipitation synthesis technique. Then, the prepared Fe3O4 NPs were characterized by different instrumental techniques for their chemical structure, purity, morphology, surface properties, and thermal behavior. The size, microstructure, and morphology of the prepared Fe3O4 NPs were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) spectroscopy, and scanning electron microscopy (SEM) equipped with an energy-dispersive X-ray spectrometer (EDS). The thermal properties of the Fe3O4 NPs were determined with thermogravimetric analysis (TGA), differential thermal analysis (DTA), and differential scanning calorimeter (DSC) analysis techniques. According to our results, there were statistically significant (p < 0.05) decreases in the velocities of spermatozoon after treatment with 400 mg/L Fe3O4 NPs. The superoxide dismutase (SOD) and catalase (CAT) activities were significant (p < 0.05) decrease after 100 mg/L in after exposure to Fe3O4 NPs in 24 h. As the doses of Fe3O4 NPs increases, the level of malondialdehyde (MDA) and total glutathione (tGSH) significantly (p < 0.05) increased at doses of 400 and 800 mg/L.

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“…In this study, the findings showed that cells transfected with SPIONs acted similarly to viability, proliferation, and differentiation of ADSC cells and these findings are in agreement with the findings obtained by Ankamwar. 60,61 A stable magnetite colloid prepared by true purification is done by magnetite separation in ultrapure water. This was the protocol used in our study and is in agreement with other studies.…”

Section: Dovepressmentioning

confidence: 99%

Homing of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) Labeled Adipose-Derived Stem Cells by Magnetic Attraction in a Rat Model of Parkinson’s Disease

Moayeri¹,

Darvishi²,

Amraei³

2020

IJN

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Introduction: Stem cell therapies for neurodegenerative diseases such as Parkinson's disease (PD) are intended to replace lost dopaminergic neurons. The basis of this treatment is to guide the migration of transplanted cells into the target tissue or injury site. The aim of this study is an evaluation of the homing of superparamagnetic iron oxide nanoparticles (SPIONs) labeled adipose-derived stem cells (ADSC) by an external magnetic field in a rat model of PD. Methods: ADSCs were obtained from perinephric regions of male adult rats and cultured in a DMEM medium. ADSC markers were assessed by immunostaining with CD90, CD105, CD49d, and CD45. The SPION was coated using poly-L-lysine hydrobromide and transfection was determined in rat ADSC using the GFP reporter gene. For this in vivo study, rats with PD were divided into five groups: a positive control group, a control group with PD (lesion with 6-HD injection), and three treatment groups: the PD/ADSC group (PD transplant with ADSCs transfected by BrdU), PD/ADSC/SPION group (PD transplant with ADSCs labeled with SPION and transfected by GFP), and the PD/ADSC/SPION/EM group (PD transplant with ADSCs labeled with SPION and transfected by GFP induced with external magnet). Results: ADSCs were immunoreactive to fat markers CD90 (90.73±1.7), CD105 (87.4±2.9) and CD49d (79.6±2.6), with negative immunostaining at the hematopoietic stem cell marker (CD45: 1.4±0.4). The efficiency of cells with SPION/PLL was about 96% of ADSC. The highest number of GFP-positive cells was in the ADSC/SPION/EM group (54.5±1.3), which was significantly different from that in ADSC/SPION group (30.83±3 and P<0.01). Conclusion: Transfection of ADSC by SPION/PLL is an appropriate protocol for cell therapy. External magnets can be used for the delivery and homing of transplanted stem cells in the target tissue.

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Dose-, Treatment- and Time-Dependent Toxicity of Superparamagnetic Iron Oxide Nanoparticles on Primary Rat Hepatocytes

Abstract: A combination of various biomarkers should be employed for the evaluation of the effect of superparamagnetic iron oxide nanoparticles on liver, and each biomarker should be analyzed in a time- and exposure-dependent manner.

Cited by 33 publications

References 82 publications

<p>The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes</p>

<p>The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes</p>

The Toxicity Assessment of Iron Oxide (Fe3O4) Nanoparticles on Physical and Biochemical Quality of Rainbow Trout Spermatozoon

<p>Homing of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) Labeled Adipose-Derived Stem Cells by Magnetic Attraction in a Rat Model of Parkinson’s Disease</p>

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