Peroxiredoxin 1 - Multifunctional antioxidant enzyme, protects from oxidative damages and increases the survival rate of mice exposed to total body irradiation

Abstract

Purpose: Peroxiredoxin 1 (Prx1) is known to be a multifunctional antioxidant enzyme playing an essential role in protecting the organism against oxidative stress. We hypothesized that administration of exogenous recombinant Prx1 may provide additional protection of the mammalian organism during the development of acute oxidative stress induced by ionizing radiation. Hence, the aim of the present work was to study the radioprotective properties of exogenous Prx1.

Materials and methods: Recombinant Prx1 was obtained by genetic engineering. The properties of Prx1 were studied using physicochemical methods. An immunoblotting and ELISA were used for the determination of the level of endogenous and exogenous Prx1 in animal blood. The survival rate of irradiated animals was assessed for 30 days with various modes of administration (intraperitoneal, intramuscular, intravenously) Prx1. Using a hematological analyzer and microscopic analysis, the changes in the level of leukocytes and platelets were assessed in animals that received and did not receive an intravenous injection of Prx1 before irradiation. Genoprotective properties of Prx1 were confirmed by micronucleus test. Real-time PCR was used to investigate the effect of Prx1 on the expression of genes involved in response to oxidative stress.

Results: Recombinant Prx1 was shown to significantly reduce oxidative damage to biological macromolecules. Prx1 is an effective radioprotector which decreases the severity of radiation-induced leuko- and thrombocytopenia, plus protects bone marrow cells from damage. The half-life of Prx1 in the bloodstream is more than 1 h, while within 1 h there is a loss of the antioxidant activity of Prx1 by almost 50%, which limits its use long (2 h) before irradiation. The introduction of Prx1 after irradiation has no significant radiomitigating effect. The most effective way of using Prx1 is intravenous administration shortly (15-30 min) before exposure to ionizing radiation, with a dose reduction factor of 1.3. Under the action of ionizing radiation a dose-dependent appearance of endogenous Prx1 in the bloodstream was also observed. The appearance of Prx1 in the bloodstream alters the expression of stress response genes (especial antioxidant response and DNA repair) in the cells of red bone marrow, promoting the activation of repair processes.

Conclusion: The recombinant Prx1 can be considered as an effective radioprotector for minimizing the risks of injury of animal's body by ionizing radiation.

Keywords: Ionizing radiation; Oxidative stress; Peroxiredoxin 1 (Prx1); Radioprotection.