Anti-aging Effects of Antioxidant Rare-Earth Orthovanadate Nanoparticles in Wistar Rats

Biomedical application of rare-earth-based nanoparticles attracts much attention due to their unique optical and redox properties and quite low toxicity. Earlier, we found age-related beneficial effects of rare-earth-based orthovanadate nanoparticles (OV NPs) on the prooxidant/antioxidant balance in liver and blood of Wistar rats, as reported by Nikitchenko et al. (Biol Trace Elem Res (2020). https://doi.org/10.1007/s12011-020-02196-7 ). However, the question remained unclear whether OV NPs' redox activity directly defines the protection ability. In the present work, antiradical, antioxidant, and membrane-protective properties of GdYVO₄/Eu³⁺ NPs (1-2 nm), GdVO₄/Eu³⁺ NPs (8 × 25 nm), LaVO₄/Eu³⁺ (57 × 8 nm) were assayed in a comparative manner in various model systems. All OV NPs demonstrated the protective properties, but extra-small GdYVO₄/Eu³⁺ NPs revealed the weakest antioxidant efficacy. In isolated mitochondria, OV NPs lowered (most evidently-extra-small NPs) respiration and oxidative phosphorylation, as well as ATP concentration. We conclude that not only the direct antioxidant effect but also slight suppression of bioenergetic processes by the OV NPs as well as the triggering of GSH-dependent antioxidant system may represent the principal mechanisms of their beneficial influences in an aged organism. This statement is consistent with improvement of the oxidative balance of 33-month-old rats due to prolonged administration of GdVO₄ /Eu³⁺ NPs (for 11 months) accompanied by retention of the GSH signaling of the old rats at the level of 12 months mature animals. Consequently, an increase of antioxidant defense upon prolonged usage of OV NPs will lead to oxidative balance stabilization increasing the health span and survival of an organism.