We studied the possibility of conductometric measurement of myelokaryocyte content in the red bone marrow of mice using a hematological Abacus Junior 5 Vet analyzer (Diatron). Statistical, correlation, and regression analyses were performed to assess of the results of myelokaryocyte counting in the suspensions of mouse red bone marrow by a direct method in cytometers and by using Abacus Junior 5 Vet analyzer. It was shown that in both intact mice and animals with modelled red bone marrow hypoplasia, irrespectively of the state of hematopoiesis in representative samples, conductometric measurements of myelokaryocyte content on the Abacus analyzer with high confidence reproduced direct counting results (in different tests p=0.64-0.82, p=0.83-0.98). This indicates that myelokaryocyte counting on the Abacus Junior 5 Vet analyzer can be an acceptable alternative to counting chamber measurements in mouse samplings. However, the variability of single measurements with the Abacus Junior 5 Vet in red bone marrow suspensions is high (5%) and this has to be considered in small samples.

According to leading experts, the vast arsenal of radioprotective agents available in the world today does not fully meet modern practical needs, both in the field of radiation protection, and in the prevention and treatment of complications of radiotherapy. The purpose of the study was to evaluate the effect of the salt-forming acids type on the radioprotective activity of NOS inhibitor T1023. The chemical part of this study included methods of chemical synthesis, physicochemical and elemental analysis. Pharmacological part – assessment of acute toxicity using V.B. Prozorovsky express method and the study of radioprotective activity using Till and McCulloch method based on the ability of mice hematopoietic cells to form spleen colonies after irradiation. The number of endogenous hematopoietic spleen colonies were assessed on the 8th day after total exposure to gamma-irradiation at a dose of 6 Gy in six independent experiments. As a result of directed chemical synthesis, six new derivatives of T1023 – salts of N-isobutanoyl-S-isopropylisothiourea have been developed, identified and characterized. The results of studying the safety and radioprotective activity of the synthesized compounds showed that changes in the salt-forming acid don’t significantly influence the toxicity: all studied compounds are in the 3rd class of toxicity and hazard. At the same time, it was found that the replacement of the salt-forming acid significantly influenced the severity of the radioprotective effect. For some of these compounds radioprotective efficacy is comparable to or exceeds the efficacy of the initial compound T1023. It is important to note that these new compounds were used in lower, more save doses than T1023. The results suggest promising further development of NOS inhibitors – isothiourea derivatives as radioprotective agents.

Лактатемия как возможный фармакологический маркер радиорезистентности при действии ингибитора NOS Т1023Макарчук В.М., Филимонова М.В., Филимонов А

The antitumor potential of a new original compound T1097 to realize a complex antineoblastic effect - NOS-inhibiting anti-angiogenic and HK2-inhibiting hypoxia-oriented cytotoxic - was investigated on the model of transplantable Ehrlich carcinoma in vivo. During the entire observation period, T1097 showed pronounced dose-dependent antitumor properties: statistically significant inhibitory effect of T1097 on the growth of tumor nodes exceeded the effect of original compound - HK2-inhibitor 3-bromopyruvate in an equimolar dose. The maximum antineoblastic effect (61%) of T1097 was obtained with its subchronic parenteral administration at a dose of 17 mg/kg and was not accompanied by the development of tumor resistance. Our findings confirm the prospects of this direction in the search for new drugs.

The purpose of the work was to study the ability of the NOS inhibitor T1023 to prevent late radiation injuries. Methods: the effects of T1023 (75 mg / kg, once i.p. 30 minutes before the irradiation) on the development of post-radiation pulmonitis and pneumofibrosis in rats with thoracic exposure to g-radiation at a dose of 12.5 Gy were studied histopathologically and morphometrically. The results of the studies showed that there wasn’t a significant objective effect of T1023 on the development of early radiation-induced lung injuries (9 weeks after irradiation). But it prevented late radiation induced lung injuaries (26 weeks after irradiation) – there were a significant lesser pathomorphological manifestations of post-radiation pulmonitis, proliferation of connective tissue and the development of fibrotic changes in the lung parenchyma. At this stage, the action of T1023 clearly contributed to the preservation of the normal histostructure of the lungs, reducing by 40% the content of compaction zones in the parenchyma. The ability of the NOS inhibitor T1023 to significantly limit the development of lungs late radiation reaction confirms the promise of further development of this compound as a means for prevention radiation therapy complications.