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Modeling the Kinetic Behavior of Reactive Oxygen Species with Cerium Dioxide Nanoparticles
Open AccessFeature PaperArticle

Antioxidant Enzyme-Mimetic Activity and Neuroprotective Effects of Cerium Oxide Nanoparticles Stabilized with Various Ratios of Citric Acid and EDTA

1
Biology Department, St. Lawrence University, Canton, NY 13617, USA
2
Psychology Department, St. Lawrence University, Canton, NY 13617, USA
3
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
4
Department of Emergency Medicine, Wright State University, Boonshoft School of Medicine, Dayton, OH 45435, USA
5
Department of Neuroscience, Cell Biology, and Physiology, Wright State University, Boonshoft School of Medicine, Dayton, OH 45435, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current Address: Department of Chemistry, University of Virginia, Charlottesville, VA 22904, USA.
Biomolecules 2019, 9(10), 562; https://doi.org/10.3390/biom9100562
Received: 14 August 2019 / Revised: 25 September 2019 / Accepted: 26 September 2019 / Published: 3 October 2019
Cerium oxide (CeO2) nanoparticles (CeNPs) are potent antioxidants that are being explored as potential therapies for diseases in which oxidative stress plays an important pathological role. However, both beneficial and toxic effects of CeNPs have been reported, and the method of synthesis as well as physico-chemical, biological, and environmental factors can impact the ultimate biological effects of CeNPs. In the present study, we explored the effect of different ratios of citric acid (CA) and EDTA (CA/EDTA), which are used as stabilizers during synthesis of CeNPs, on the antioxidant enzyme-mimetic and biological activity of the CeNPs. We separated the CeNPs into supernatant and pellet fractions and used commercially available enzymatic assays to measure the catalase-, superoxide dismutase (SOD)-, and oxidase-mimetic activity of each fraction. We tested the effects of these CeNPs in a mouse hippocampal brain slice model of ischemia to induce oxidative stress where the fluorescence indicator SYTOX green was used to assess cell death. Our results demonstrate that CeNPs stabilized with various ratios of CA/EDTA display different enzyme-mimetic activities. CeNPs with intermediate CA/EDTA stabilization ratios demonstrated greater neuroprotection in ischemic mouse brain slices, and the neuroprotective activity resides in the pellet fraction of the CeNPs. The neuroprotective effects of CeNPs stabilized with equal proportions of CA/EDTA (50/50) were also demonstrated in two other models of ischemia/reperfusion in mice and rats. Thus, CeNPs merit further development as a neuroprotective therapy for use in diseases associated with oxidative stress in the nervous system. View Full-Text
Keywords: cerium dioxide; nanoceria; ROS; catalase; superoxide dismutase; ischemia; angiotensin II; neuroprotection cerium dioxide; nanoceria; ROS; catalase; superoxide dismutase; ischemia; angiotensin II; neuroprotection
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Estevez, A.Y.; Ganesana, M.; Trentini, J.F.; Olson, J.E.; Li, G.; Boateng, Y.O.; Lipps, J.M.; Yablonski, S.E.R.; Donnelly, W.T.; Leiter, J.C.; Erlichman, J.S. Antioxidant Enzyme-Mimetic Activity and Neuroprotective Effects of Cerium Oxide Nanoparticles Stabilized with Various Ratios of Citric Acid and EDTA. Biomolecules 2019, 9, 562.

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