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A radioprotective effect of exogenous recombinant peroxiredoxin 2 (Prx2) was revealed and characterized using an animal model of whole body X-ray irradiation at sublethal and lethal doses. Prx2 belongs to an evolutionarily ancient family of peroxidases that are involved in enzymatic degradation of a wide variety of organic and inorganic hydroperoxides. Apart from that, the oxidized form of Prx2 also exhibits chaperone activity, thereby preventing protein misfolding and aggregation under oxidative stress. Intravenous administration of Prx2 in animals at a concentration of 20 µg/g 15 min before exposure to ionizing radiation contributes to a significantly higher survival rate, suppresses the development of leucopenia and thrombocytopenia, as well as protects the bone marrow cells from genome DNA damage. Moreover, injection of Prx2 leads to suppression of apoptosis, stimulates cell proliferation and results in a more rapid recovery of the cell redox state. Exogenous Prx2 neutralizes the effect of the priming dose on the second irradiation of the cells. The radioprotective properties of exogenous Prx2 are stipulated by its broad substrate peroxidase activity, chaperone activity in the oxidized state, and are also due to the signal-regulatory function of Prx2 mediated by the regulation of the level of hydroperoxides as well as via interaction with redox-sensitive regulatory proteins., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aqueous solutions of highly stable supramolecular donor-acceptor complexes of chemically nonmodified pristine C(60) fullerene molecules with H(2)O molecules (hydrated C(60) fullerene-C(60)HyFn) and their labile nano-sized clusters were examined for their antioxidant effects on removal of hydroxyl radicals (.OH) and protecting DNA against oxidative damage induced by ionizing radiation in vitro. The suppressing influence of C(60)HyFn on the formation of OH-radicals in water exposed to X-rays at doses of 1-7 Gy was assessed by determination of oxidation levels of coumarin-3-carboxylic acid. C(60)HyFn demonstrates apparent antiradical activity in vitro in the range of concentrations of 10(-11)-10(-6) M. Paradoxically, the .OH-removing efficacy of C(60)HyFn was in reverse correlation with fullerene concentration. It was hypothesized that the antiradical action of C(60)HyFn in water medium generally is due to a "nonstoichiometric" mechanism, supposedly to a hydrated free radical recombination (self-neutralization), which is catalyzed by specific water structures ordered by C(60)HyFn. With the use of 8-oxoguanine as a marker of oxidative damage to DNA, it has been demonstrated that C(60)HyFn in concentrations of 10(-7)-10(-6) M protects nucleic acids against radical-induced damage. The second part of the present study was aimed to evaluate the overall radioprotective efficacy of C(60)HyFn in doses of 0.1 or 1 mg/kg b.w. injected intraperitoneally to mice either 1 h before or 15 min after lethal dose exposure of the X-ray (7 Gy) irradiation. Survival rate of the mice was observed at 30 day intervals after irradiation, while the weight gains of experimental animals were monitored as well. The most significant protective effect was demonstrated when 1 mg/kg dosage of C(60)HyFn was administered before irradiation. The outcome of the substance testing is 15% survival rate of irradiated animals at 30 days of observation, and prevention of noticeable weight loss characteristic for radiation impact, versus unprotected control animals. In conclusion, results of the study obviate that the apparent protective action of C(60)HyFn in vivo is determined by its considerable ability to decrease X-ray-generated reactive oxygen species. Based on the results and that neat C(60) is nontoxic, actually in the hydrated form, without side effects and with sufficient radioprotective effects in low doses, C(60)HyFn may be considered as a novel antioxidant agent, which substantially diminishes the harmful effects of ionizing radiation.