60 - Iron-sulfur [2Fe-2S] nitrosyl complexes as new trend in synthesis of donors of nitric oxide for anti-aging therapy

Abstract

Aging is associated with 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 (NO) radicals. Our approach to the problems of anti-aging therapy is based on the iron-sulfur nitrosyl complexes as the donors of NO. Some of them demonstrate the anti-cancer properties (Sanina, Aldoshin, 2011). Moreover, the water-soluble polyvinylpyrrolidone composites containing the iron sulfur nitrosyl complexes with the antitumor and antiseptic activities were synthesized as potential long-living transport agents of NO (Shmatko et al., 2015). Here, we present geroprotective effects of Na2[Fe2(S2O3)2(NO)4]·4H2O (FeSNO) as the NO donor. Wistar male rats, 24 months age, were daily administered for 14 days intraperitoneally with FeSNO, 5 mg/kg of mass in 1.0 ml of physiological solution or with 1.0 ml of the physiological solution (control animals). The service for 605 days has proved that the administration with FeSNO increases survivorship of the rats about 30 percent as compared to the control animals. Furthermore, the rats of 7-8 months age were subjected to X-ray irradiation (5 Gy) after which the irradiated animals were daily intraperitoneally administered with FeSNO for 30 days, 5 mg/kg of mass, or with the physiological solution (control animals). Then, malonyldialdehyde (MDA) and the antioxidant enzymes superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (GPO) and glutathione reductase (GR) as the oxidative stress indicators were measured in liver, heart and brain tissues of the animals. It was revealed that the administration of FeSNO restores the negative impacts of irradiation on the level of MDA and the activities of SOD, Cat, GPO and GR. Thus, the nitrosyl complexes with the functionalized sulfur-containing ligands can be recommended as the potential drugs for anti-aging medicine. Furthermore, the polymer composites of the [2Fe-2S] nitrosyl complexes hold considerable promise as the drug delivery systems for NO-based therapy.