Toxicological Implications of Platinum Nanoparticle Exposure: Stimulation of Intracellular Stress, Inflammatory Response, and Akt Signaling In Vitro

Labrador-Rached, Claudia J.; Browning, Rebecca T.; Braydich‐Stolle, Laura K.; Comfort, Kristen K.

doi:10.1155/2018/1367801

Cited by 31 publications

(21 citation statements)

References 36 publications

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“…The entire reaction was completed within 2 h due to the presence of pure phenolic compounds in the solution. The single sharp peak at 300 nm was attributed to the excitations of surface plasmon vibrations, indicating the synthesis of PtNPs (Figure 1A), which is in agreement with the results of previous reports [41,42]. Several studies have reported that metal nanoparticles can be synthesized using biomolecules as reducing and stabilizing agents.…”

Section: Resultssupporting

confidence: 90%

The Effects of Apigenin-Biosynthesized Ultra-Small Platinum Nanoparticles on the Human Monocytic THP-1 Cell Line

Gurunathan

Jeyaraj

Kang

et al. 2019

Cells

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Generally, platinum nanoparticles (PtNPs) are considered non-toxic; however, toxicity depends on the size, dose, and physico-chemical properties of materials. Owing to unique physico-chemical properties, PtNPs have emerged as a material of interest for several biomedical applications, particularly therapeutics. The adverse effect of PtNPs on the human monocytic cell line (THP-1) is not well-established and remains elusive. Exposure to PtNPs may trigger oxidative stress and eventually lead to inflammation. To further understand the toxicological properties of PtNPs, we studied the effect of biologically synthesized ultra-small PtNPs on cytotoxicity, genotoxicity, and proinflammatory responses in the human monocytic cell line (THP-1). Our observations clearly indicated that PtNPs induce cytotoxicity in a dose-dependent manner by reducing cell viability and proliferation. The cytotoxicity of THP-1 cells correlated with an increase in the leakage of lactate dehydrogenase, generation of reactive oxygen species, and production of malondialdehyde, nitric oxide, and carbonylated proteins. The involvement of mitochondria in cytotoxicity and genotoxicity was confirmed by loss of mitochondrial membrane potential, lower ATP level, and upregulation of proapoptotic and downregulation of antiapoptotic genes. Decreases in the levels of antioxidants such as reduced glutathione (GSH), oxidized glutathione (GSH: GSSG), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and thioredoxin (TRX) were indicative of oxidative stress. Apoptosis was confirmed with the significant upregulation of key apoptosis-regulating genes. Oxidative DNA damage was confirmed by the increase in the levels of 8-oxodG and 8-oxoG and upregulation of DNA damage and repair genes. Finally, the proinflammatory responses to PtNPs was determined by assessing the levels of multiple cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1). All the cytokines were significantly upregulated in a dose-dependent manner. Collectively, these observations suggest that THP-1 cells were vulnerable to biologically synthesized ultra-small PtNPs.

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Section: Resultssupporting

confidence: 90%

The Effects of Apigenin-Biosynthesized Ultra-Small Platinum Nanoparticles on the Human Monocytic THP-1 Cell Line

Gurunathan

Jeyaraj

Kang

et al. 2019

Cells

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“…Platinum NPs induce ROS generation by impairing receptor activator of nuclear factor κB ligand (RANKL) signaling [48]. For instance, incubating HepG2 cells with 68-nm PtNPs suggested that ROS are dose-dependently induced [34]. Ultra-small PtNPs also induce ROS generation in THP-1 cells [22].…”

Section: Platinum-based Nps Induce Ros Lipid Peroxidation (Lpo) Nitmentioning

confidence: 99%

“…Platinum NPs induce size-dependent toxicity in neuroblastoma, MDA-MB-231, and LNCaP cells, indicating that the diameter of these NPs plays a crucial role in cytotoxicity [33]. Graphene oxide and vanillin-functionalized graphene oxide induce pro-inflammatory cytokines in a human acute monocytic leukemia cell line [22], and PtNPs dose-dependently induce cytokines such as IL-1β, IL-8, and tumor necrosis factor alpha (TNFα) [34].…”

Section: Introductionmentioning

confidence: 99%

Anisotropic Platinum Nanoparticle-Induced Cytotoxicity, Apoptosis, Inflammatory Response, and Transcriptomic and Molecular Pathways in Human Acute Monocytic Leukemia Cells

Gurunathan

Jeyaraj

et al. 2020

IJMS

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The thermoplasmonic properties of platinum nanoparticles (PtNPs) render them desirable for use in diagnosis, detection, therapy, and surgery. However, their toxicological effects and impact at the molecular level remain obscure. Nanotoxicology is mainly focused on the interactions of nanostructures with biological systems, particularly with an emphasis on elucidating the relationship between the physical and chemical properties such as size and shape. Therefore, we hypothesized whether these unique anisotropic nanoparticles could induce cytotoxicity similar to that of spherical nanoparticles and the mechanism involved. Thus, we synthesized unique and distinct anisotropic PtNPs using lycopene as a biological template and investigated their biological activities in model human acute monocytic leukemia (THP-1) macrophages. Exposure to PtNPs for 24 h dose-dependently decreased cell viability and proliferation. Levels of the cytotoxic markers lactate dehydrogenase and intracellular protease significantly and dose-dependently increased with PtNP concentration. Furthermore, cells incubated with PtNPs dose-dependently produced oxidative stress markers including reactive oxygen species (ROS), malondialdehyde, nitric oxide, and carbonylated protein. An imbalance in pro-oxidants and antioxidants was confirmed by significant decreases in reduced glutathione, thioredoxin, superoxide dismutase, and catalase levels against oxidative stress. The cell death mechanism was confirmed by mitochondrial dysfunction and decreased ATP levels, mitochondrial copy numbers, and PGC-1α expression. To further substantiate the mechanism of cell death mediated by endoplasmic reticulum stress (ERS), we determined the expression of the inositol-requiring enzyme (IRE1), (PKR-like ER kinase) PERK, activating transcription factor 6 (ATF6), and activating transcription factor 4 ATF4, the apoptotic markers p53, Bax, and caspase 3, and the anti-apoptotic marker Bcl-2. PtNPs could activate ERS and apoptosis mediated by mitochondria. A proinflammatory response to PtNPs was confirmed by significant upregulation of interleukin-1-beta (IL-1β), interferon γ (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL-6). Transcriptomic and molecular pathway analyses of THP-1 cells incubated with the half maximal inhibitory concentration (IC50) of PtNPs revealed the altered expression of genes involved in protein misfolding, mitochondrial function, protein synthesis, inflammatory responses, and transcription regulation. We applied transcriptomic analyses to investigate anisotropic PtNP-induced toxicity for further mechanistic studies. Isotropic nanoparticles are specifically used to inhibit non-specific cellular uptake, leading to enhanced in vivo bio-distribution and increased targeting capabilities due to the higher radius of curvature. These characteristics of anisotropic nanoparticles could enable the technology as an attractive platform for nanomedicine in biomedical applications.

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“…The authors observed that high doses of PtNPs (70 nm, citrate coated) induced HepG2 cytotoxicyty. Lower concentrations did not induce direct toxicity, but the combined presence of intracellular stress, active inflammatory responses with upregulated signal transduction might have influence on long-term health hazards [42].…”

Section: In Vitro Studiesmentioning

confidence: 90%

Are platinum nanoparticles safe to human health?

Czubacka

Czerczak

2019

Med Pr

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Platinum nanoparticles (PtNPs) have been widely used not only in industry, but above all in medicine and diagnostics. However, there are disturbing reports related to the toxic effects of nanoplatinum, which is the main reason why the authors of this study have decided to review and analyze literature data related to its toxicity and impact on human health. While PtNPs may be absorbed by the respiratory and digestive tract, and can penetrate through the epidermis, there is no evidence concerning their absorption through the skin. Platinum nanoparticles accumulate mainly in the liver and spleen although they also reach other internal organs, such as lungs, kidneys or heart. Toxicokinetics of platinum nanoparticles depends strongly on the particle size. Only few studies regarding platinum nanoparticles toxicity have been conducted. Animals intratracheally exposed to platinum nanoparticles have demonstrated an increased level of proinflammatory cytokines in bronchoalveolar lavage which confirms inflammatory response in the lungs. Oral administration of PtNPs can cause inflammatory response and induce oxidative stress. Nanoplatinum has been found to induce hepatotoxicity and nephrotoxicity via the intravenous route. It can cause DNA damage and cellular apoptosis without significant cytotoxicity. There are no research studies on its carcinogenicity. Fetal or maternal toxicity has not been observed, but an increased mortality and a decreased growth of the offspring have been demonstrated. Platinum nanoparticles may permeate the skin barrier but there is no evidence for their absorption. Due to the insufficient number of tests that have been carried out to date, it is not possible to clearly determine the occupational exposure limit value; however, caution is recommended to employees exposed to their effects.

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Toxicological Implications of Platinum Nanoparticle Exposure: Stimulation of Intracellular Stress, Inflammatory Response, and Akt Signaling In Vitro

Cited by 31 publications

References 36 publications

The Effects of Apigenin-Biosynthesized Ultra-Small Platinum Nanoparticles on the Human Monocytic THP-1 Cell Line

The Effects of Apigenin-Biosynthesized Ultra-Small Platinum Nanoparticles on the Human Monocytic THP-1 Cell Line

Anisotropic Platinum Nanoparticle-Induced Cytotoxicity, Apoptosis, Inflammatory Response, and Transcriptomic and Molecular Pathways in Human Acute Monocytic Leukemia Cells

Are platinum nanoparticles safe to human health?

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