Abstract
Due to its unique redox chemistry, nanoceria is considered as potent free radical scavenger and antioxidant. However, their protective capacity in aging organisms remains controversial. To detect the anti-aging effects associated with the redox activity of 2 and 10 nm nano-CeO2, different test systems were used, including in vitro analysis, in situ assay of mitochondria function and in vivo studies of suitable nano-CeO2 on aging of male Wistar rats from 22 months-old to the end of life. The 2 nm nanoparticles exhibited not only antioxidant (·OH scavenging; chemiluminescence assay; decomposition of H2O2, phosphatidylcholine autooxidation) but also prooxidant properties (reduced glutathione and reduced nicotinamide adenine dinucleotide phosphate oxidation) as well as affected mitochondria whereas in most test systems 10 nm nano-CeO2 showed less activity or was inert. Prolonged use of the more redox active 2 nm nano-CeO2 (0.25–0.3 mg/kg/day) in vivo with drinking water resulted in improvement in physiological parameters and normalization of the prooxidant/antioxidant balance in liver and blood of aging animals. Survival analysis using Kaplan–Meier curve and Gehan tests with Yates' correction showed that by the time the prooxidant-antioxidant balance was assessed (32 months), survival rates exceeded the control values most considerably. The apparent median survival for the control rats was 900 days, and for the experimental rats—960 days. In general, the data obtained indicate the ability of extra-small 2 nm nano-CeO2 to improve quality of life and increase the survival rate of an aging organism.
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The datasets generated during and/or analyzed during the current study are available from the corresponding authors on reasonable request.
Abbreviations
- Aco:
-
Aconitase
- CD:
-
Conjugated dienes
- CR:
-
Calorie restricted diet
- CR-mimetics:
-
Calorie restriction mimetics
- G-6-PDG:
-
Glucose-6-phosphate dehydrogenase
- GPx:
-
Glutathione peroxidase
- GR:
-
Glutathione reductase
- Grx:
-
Glutaredoxin
- ICDG:
-
Isocitrate dehydrogenase
- LHPO:
-
Lipid hydroperoxide
- LPO:
-
Lipid peroxidation
- MC:
-
Mitochondrial fraction of liver
- MDA:
-
Malonic dialdehyde
- MDG:
-
Malate dehydrogenase
- NADPH:
-
Reduced nicotinamide adenine dinucleotide phosphate
- NPs:
-
Nanoparticles
- PCh:
-
Phosphatidylcholine
- PMC:
-
Post-mitochondrial fraction of liver
- R.C.I.:
-
Respiratory control index
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The authors strongly appreciated to Mrs. Olga Sedyh for her assistance with nanoparticles synthesis.
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This work was supported by National Academy of Sciences of Ukraine (Project № 0117U000989), National Academy of Sciences of Ukraine (Development of multifunctional nanomaterials with controlled properties for biomedical and technical applications (code: Immortel)), State Fund for Fundamental Research (project № Ф64/29–2016).
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The idea of the research was developed by YN, VS, and AB with the assistance of VK, NSK, and SY. Nanocrystals were synthesized by VK. In vitro and in situ tests were carried out by YN, NSK, and VK. In vivo tests were carried out by YN, IN, NK. YN, NSK, IN and NK drafted the manuscript text. All authors have read and approved the final manuscript.
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All manipulations with animals were carried out in accordance with The International Convention of working with animals and Ukraine Law “On animals protection from cruel treatment”. The Commission on Bioethics of the Research Institute of Biology of V. N. Karazin Kharkiv National University found no violations during the research work (protocol № 8 of 19.10.2017).
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Nikitchenko, Y.V., Klochkov, V.K., Kavok, N.S. et al. CeO2 nanoparticles improve prooxidant/antioxidant balance, life quality and survival of old male rats. Biogerontology 24, 47–66 (2023). https://doi.org/10.1007/s10522-022-09987-6
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DOI: https://doi.org/10.1007/s10522-022-09987-6