The new synthesized Cu(II) chelates of amino acids Schiff bases were studied as a potential radioprotectors. Male albino rats of Wistar strain were exposed to X-ray whole-body irradiation at 4.8 Gy. This dose caused 30% mortality of the animals (LD30). The survival of animals exposed to radiation after preliminary administration of 10 mg/kg Cu(II)(Nicotinyl-L-Tyrosinate)2 or Cu(II)(Nicotinyl-L-Tryptophanate)2 prior to irradiation was registered about 80 and 100% correspondingly. Using spectrophotometric melting and agarose gel electrophoresis methods, the differences between the DNA isolated from irradiated rats and rats pretreated with Cu(II) chelates were studied. The fragments of DNA with different breaks were revealed in DNA samples isolated from irradiated animals. While, the repair of the DNA structure was observed for animals pretreated with the Cu(II) chelates. The results suggested that pretreatment of the irradiated rats with Cu(II)(Nicotinyl-L-Tyrosinate)2 and Cu(II)(Nicotinyl-L-Tryptophanate)2 compounds improves the liver DNA characteristics.

This research was performed to determine whether or not treatment of burn-injured rats with Cu(II)2(3,5-diisopropylsalicylate)4(Cu(II)2(3,5-DIPS)4) facilitated recovery from burn-injury. Four groups of adult male rats received a standard skin burn 1 h before an initial subcutaneous treatment which was continued daily for three days with either 0, 5, 10 or 20micromol Cu(II)2(3,5-DIPS)4/kg body mass. A fifth group was given no treatment. A sixth group served as a non-burn-injured non-treated normal control group. At 3 h and on days 1, 2, 3, 7 and 14 post-burn-injury blood samples were obtained from rats in all groups for the determination of leukocyte, platelet and erythrocyte counts, clotting times, hemoglobin and hematocrit values. Total protein and middle mass peptides in plasma, as well as plasma lipid and erythrocyte membrane peroxidation products were determined on days 7 and 14. Burn wound healing and body mass were determined daily from day 0 to 6 with a notation of crust rejection by day 14. Treatment with Cu(II)2(3,5-DIPS)4 produced effects consistent with a facilitation of Cu-dependent immune-mediated physiological inflammatory responses to burn injury. It is concluded that treatment of burn injury with Cu(II)2(3,5-DIPS)4 supports Cu-dependent physiological responses involved in overcoming burn injury, which may have been further optimized by continued treatment beyond day 2, the last day of treatment.

Essential metalloelement chelates presents a promising class of compounds for search and development of novel anti-radiation agents, study of which offers a new approach to overcome the pathological effects of ionizing radiation. In this study Cu(II) chelates of Nicotinyl-L-Tyrosinate and Nicotinyl-L-Tryptophanate Schiff Bases were synthesized and investigated as radioprotectors in animal experiments against injuries caused by ionizing irradiation. Based on the assessment of average life-span indices and 30-day animal survival after radiation exposure at LD50/30 (4.8 Gy) or LD100/30 (8.7 Gy) the radioprotective effects of 0 mg/kg (Vehicle), 10 mg/kg, 20 mg/kg, or 40 mg/kg Cu(II)(Nicotinyl-L-Tyrosinate)2 or Cu(II)(Nicotinyl-L-Tryptophanate)2 as well as their parents Schiff Bases were studied in case of single subcutaneous and oral administration to rats 1, 3, 6 and 24 hours prior to X-ray irradiation. The mixture of 4% propylene glycol and 1.4% polyvinyl alcohol in saline was used as a Vehicle for the administration of compounds to animal organism. According to the results obtained, administration of the metallochelates to the rat organism prior to X-ray irradiation provided strong radioprotective effects expressed upon application of all considered dose, mode and time treatment schedules: in groups of animals treated with Cu(II) chelates there was an remarkable increase in the indices of survival and average life-span in a 30-day period post exposure compared to the control Vehicle treated -irradiated rats. The appropriate parents Schiff Bases Nicotinyl-L-Tyrosinate and Nicotinyl-LTryptophanate also exerted the radioprotective action. However, these compounds were active as effective radioprotectors only in case X-ray irradiation at a dose level equal to or less than LD50/30. Data of analyses indicated that Cu(II) chelates as well as their initial amino acid Schiff Bases did not avert the development of disturbances of hematological indices of animals exposed at LD50/30. However, the findings of immunological studies have demonstrated the inhibiting effects of these compounds on circulating immune complexes (CICs) in blood plasma, which are the major mediators of immune response and are considered as indicators of the autoimmune and inflammatory components of radiation-induced upregulated immune response. Unlike to Nicotinyl-L-Aminoacidate Schiff Bases their corresponding Cu(II) chelates diminished the harmful effects of radiation-induced CICs formation not only in case of irradiation at LD50/30, but also at much higher radiation dose levels. Thus, the single administration of Cu(II)(Nicotinyl-LTyrosinate)2 and Cu(II)(Nicotinyl-L-Tryptophanate)2 at non-toxic doses provides effective radiation protection and high level of survival of exposed animals. Research is performed in the frames of ISTC A-1321 Project.

To reveal protective role of the new Mn(II) complexes with Nicotinyl-L-Tyrosinate and Nicotinyl-L-Tryptophanate Schiff Bases against ionizing radiation. The DNA of the rats liver was isolated on 7, 14, and 30 days after X-ray irradiation. The differences between the DNA of irradiated rats and rats pre-treated with Mn(II) complexes were studied using the melting, microcalorimetry, and electrophoresis methods. The melting parameters and the melting enthalpy of rats livers DNA were changed after the X-ray irradiation: melting temperature and melting enthalpy were decreased and melting interval was increased. These results can be explained by destruction of DNA molecules. It was shown that pre-treatment of rats with Mn(II) complexes approximates the melting parameters to norm. Agarose gel electrophoresis data confirmed the results of melting studies. The separate DNA fragments were revealed in DNA samples isolated from irradiated animals. The DNA isolated from animals pre-treated with the Mn(II) chelates had better electrophoretic characteristics, which correspond to healthy DNA. Pre-treatment of the irradiated rats with Mn(II)(Nicotinil-L-Tyrosinate) and Mn(II)(Nicotinil-L-Tryptophanate)2 improves the DNA characteristics.

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