167 - New Agents for Anti-Aging and Anti-Radiation Therapy Based on the Binuclear Thionitrosyl-Iron Complexes

Abstract

Aging is associated with the dysfunctions in vascular smooth muscle cells, neurotransmission, renal and immune systems, to name just a few, many of which stems from decline in reliability of the regulatory functions of nitric oxide radical (NO). Our approach to creation of a new class of agents for anti-aging and anti-radiation therapy is based on the design of the novel nitric oxide donors, i.e. – Fe-thionitrosyl complexes which are considered as long-living reservoirs and transport agents of NO in living cells. It was previously shown that such the complexes demonstrate the anti-cancer properties (Sanina, Aldoshin, 2011). Here, we present evidences of geroprotective and radioprotective effects of the synthetic NO-complex, Na2[Fe2(S2O3)2(NO)4]·4H2O (FeSNO). Wistar male rats, age of which was 24 months at the beginning of the experiments, were daily administered intraperitoneally with FeSNO, 5 mg/kg of mass in 1.0 ml of physiological solution (experimental animals) or administered with 1.0 ml of physiological solution (control animals) for 14 days. The prolonged service testing, for 605 days, has proved that the administration of rats with FeSNO gives the extended survivorship, about 30 percentages more, as compared to the control animals. Furthermore, the adult rats of age of 7-8 months were subjected to the acute irradiation with X-rays (5 Gy dose) after which the irradiated animals were intraperitoneally administered daily for 30 days with FeSNO, 5 mg/kg of mass in 1.0 ml of physiological solution (experimental animals) or with 1.0 ml of physiological solution (control animals). Thereafter, the important indicators of oxidative stress, i.e. – the level of malonyldialdehyde (MDA) and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (GPO) and glutathione reductase (GR) were measured in liver, heart and brain tissues of animals of both groups, the experimental and the control ones. It was revealed that the administration of FeSNO after irradiation of animals restores the negative impacts of the sublethal dose of X-rays on the level of MDA and the activities of SOD, Cat, GPO and GR in tissues of the irradiated animals. Thus, the nitrosyl complexes of iron with the functionalized sulfur-containing ligands hold considerable promise as the potential agents in creating novel drugs for anti-aging and anti-radiation medicine.