The Effect of Cerium Oxide Nanoparticle Valence State on Reactive Oxygen Species and Toxicity

Dunnick, Katherine M.; Pillai, Rajalekshmi C.; Pisane, Kelly L.; Stefaniak, Aleksandr B.; Sabolsky, Edward M.; Leonard, Stephen S.

doi:10.1007/s12011-015-0297-4

Cited by 89 publications

(66 citation statements)

References 27 publications

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“…Previous studies have shown that CeO 2 nanoparticles in therapeutic doses are non-toxic [14], relatively stable and accumulate in liver upon intravenous injection [15]. While some studies demonstrated toxicity of CeO 2 nanoparticles in high doses [16], it has now been shown that the toxicity is based on whether the particles exist in Ce +3 or Ce +4 and the relative ratio of Ce +3 /Ce +4 [17]. Furthermore, several studies have shown that CeO 2 nanoparticles can be used to treat stroke [18], ovarian cancer [19], cardiomyopathy [20], sepsis [21] and obesity [22].…”

Section: Introductionmentioning

confidence: 99%

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

Manne¹,

Arvapalli

Graffeo³

et al. 2017

Cell Physiol Biochem

554

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Background: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO 2 ) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO 2 nanoparticles on hepatic ischemia reperfusion injury. Methods: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO 2 nanoparticle only, hepatic ischemia reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO 2 nanoparticle group (IR+ CeO 2 ). Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. Results: Prophylactic treatment with CeO 2 nanoparticles (0.5mg/kg i.v (IR+CeO 2 group)) 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. Conclusion: Taken together, these data suggest that CeO 2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic agent to prevent hepatic injury associated with graft failure.Room 315,

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Section: Introductionmentioning

confidence: 99%

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

Manne¹,

Arvapalli

Graffeo³

et al. 2017

Cell Physiol Biochem

554

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“…Nanoceria has a large number of surface defects due to oxygen vacancies at its surface, which exponentially increase per gram of material as particle size decreases 11,21,22 . Thus, ceria nanoparticles have a natural tendency to agglomerate when its surface is not functionalized.…”

Section: Introductionmentioning

confidence: 99%

pH-Dependent Activity of Dextran-Coated Cerium Oxide Nanoparticles on Prohibiting Osteosarcoma Cell Proliferation

Alpaslan

Yazıcı

Golshan

et al. 2015

ACS Biomater. Sci. Eng.

117

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Cerium oxide nanoparticles (or nanoceria) have demonstrated great potential as antioxidants in various cell culture models. Despite such promise for reducing reactive oxygen species and ability for surface functionalization, nanoceria has not been extensively studied for cancer applications to date. Herein, we engineered the surface of nanoceria with dextran and observed its activity in the presence bone cancer cells (osteosarcoma cells) at different pH values resembling the cancerous and non-cancerous environment. We found that dextran coated nanoceria was much more effective at killing bone cancer cells at slightly acidic (pH=6) compared to physiological and basic pH values (pH=7 and pH=9). In contrast, minimal toxicity was observed for healthy (noncancerous) bone cells when cultured with nanoceria at pH=6 after one day of treatment in the concentration range of 10-1000 µg/mL. Although healthy bone cancer cell viability decreased after treatment with high ceria nanoparticle concentrations (250-1000 µg/mL) for longer time periods at pH=6 (3 days and 5 days), approximately 2-3 fold higher healthy bone cell viabilities were observed compared to osteosarcoma cell viability at similar conditions. Very low toxicity was observed for healthy osteoblasts cultured with nanoceria for any concentration at any time period at pH=7. In this manner, this study provides the first evidence that nanoceria can be a promising nanoparticle for treating bone cancer without adversely affecting healthy bone cells and, thus, deserves further investigation.

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“…Gd-doped CeO 2 nanopowder was prepared as previously described (Dunnick et al, 2015). Briefly, a hydrothermal method was used in which cerium (IV) ammonium nitrate and gadolinium nitrate hexahydrate were dissolved in deionized water and mixed together.…”

Section: Methodsmentioning

confidence: 99%

“…X-ray photoelectron spectroscopy (XPS) was utilized to determine the changes in valence state between samples as previously described (Dunnick et al, 2015). To determine the relative size of the nanoparticles in phosphate-buffered saline (PBS), dynamic light scattering (DLS) was performed using a Nano ZS90 instrument (Malvern Instruments, Worcestershire, UK).…”

Section: Methodsmentioning

confidence: 99%

“…Pure, unaltered CeO 2 nanoparticles were also tested in addition to a Gd 2 O 3 nanoparticle control to ensure any effects seen between compounds were due to valence state and oxygen vacancies rather than the presence of Gd 2 O 3 , which is known to induce acute lung toxicity (Yoneda et al, 1995). Initial in vitro tests by our group determined that as particle doping increased, the antioxidant potential of CeO 2 nanoparticles decreased in both RLE-6TN alveolar epithelial and NR8383 alveolar macrophage rat cells (Dunnick et al, 2015). Others have also shown that valence state had no effect on in vitro toxicity, but as the 3+ / 4+ ratio decreased, the antioxidant potential of the nanoparticles also decreased (Celardo et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the effect of valence state on cerium oxide nanoparticle toxicity following intratracheal instillation in rats

et al. 2016

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Cerium (Ce) is becoming a popular metal for use in electrochemical applications. When in the form of cerium oxide (CeO2), Ce can exist in both 3 + and 4 + valence states, acting as an ideal catalyst. Previous in vitro and in vivo evidence have demonstrated that CeO2 has either anti- or pro-oxidant properties, possibly due to the ability of the nanoparticles to transition between valence states. Therefore, we chose to chemically modify the nanoparticles to shift the valence state toward 3+. During the hydrothermal synthesis process, 10 mol% gadolinium (Gd) and 20 mol% Gd, were substituted into the lattice of the CeO2 nanoparticles forming a perfect solid solution with various A-site valence states. These two Gd-doped CeO2 nanoparticles were compared to pure CeO2 nanoparticles. Preliminary characteristics indicated that doping results in minimal size and zeta potential changes but alters valence state. Following characterization, male Sprague-Dawley rats were exposed to 0.5 or 1.0 mg/kg nanoparticles via a single intratracheal instillation. Animals were sacrificed and bronchoalveolar lavage fluid and various tissues were collected to determine the effect of valence state and oxygen vacancies on toxicity 1-, 7-, or 84-day post-exposure. Results indicate that damage, as measured by elevations in lactate dehydrogenase, occurred within 1-day post-exposure and was sustained 7-day post-exposure, but subsided to control levels 84-day post-exposure. Furthermore, no inflammatory signaling or lipid peroxidation occurred following exposure with any of the nanoparticles. Our results implicate that valence state has a minimal effect on CeO2 nanoparticle toxicity in vivo.

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The Effect of Cerium Oxide Nanoparticle Valence State on Reactive Oxygen Species and Toxicity

Cited by 89 publications

References 27 publications

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

pH-Dependent Activity of Dextran-Coated Cerium Oxide Nanoparticles on Prohibiting Osteosarcoma Cell Proliferation

Evaluation of the effect of valence state on cerium oxide nanoparticle toxicity following intratracheal instillation in rats

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