INFLUENCE OF COMBINED ACTION OF X-RADIATION AND CYCLOOXYGENASE-2 - MELOXIVET INHIBITOR ON VEGF AND PGE-2 CONTENT IN BLOOD OF RAT-TUMOR CARRIERS. / VPLYV KOMBINOVANOÏ DIÏ Kh-VYPROMINENNIa TA INGIBITORA TsYKLOOKSYGENAZY-2 ­ MELOKSYVETU NA VMIST VEGF TA PGE-2 U SYROVATTsI KROVI ShchURIV-PUKhLYNONOSIÏV.

OBJECTIVE: The objective of this work was to study the effect of the combined action of X-radiation and the cyclooxygenase-2 (COX-2) inhibitor on the level of vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE-2) in blood serum of rat-tumor carriers at irradiation in different doses. MATERIALS AND METHODS: 20 tumor-bearing rats of the Wistar population weighing 160-180 g, with transplanted Guerin carcinoma, fractionated irradiation (5 Gy + 5 Gy) and (0.5 Gy + 0.5 Gy) of the tumor growth zone on the RUM- 17 was carried out, with an interval between sessions of 24 hours. The drug «Meloxivet¼ - a selective inhibitor of cyclooxygenase-2 was administered 24 hours before irradiation and 2 hours before the second exposure (0.2 mg per 1 kg body weight). Blood sampling was performed by the method of life-time decapitation after 24 hours after the last fraction of irradiation. The content of VEGF in blood serum was determined by the method of enzyme immunoas- say using standardResults. After fractionated irradiation in a total dose of 1 Gy (0.5 Gy + 0.5 Gy), the level of VEGF was increased by 1.5 times compared with intact control, and in animals that were irradiated in a total dose of 10 Gy (5 Gy + 5 Gy ), the VEGF level was reduced by 1.92 times. That is, there was a difference in the content of VEGF in blood serum of rat tumor carriers, depending on the dose of irradiation: in a total dose of 1 Gy - stimulation of angiogenesis, and in the total dose of 10 Gy - a significant slowdown in this process. In the case of combined exposure to radiation (10 Gy) and the COX-2 inhibitor, meloxivet, the potential decrease in VEGF levels was 3.49 times compared to con- trol and 1.8 times with isolated exposure. At the same time, the level of PGE-2 also decreased with respect to iso- lated exposure by 1.5 times, indicating COX-2 inhibition. With a combined low dose (1 Gy) irradiation and COX-2- meloxivet inhibitor, VEGF levels were reduced by 1.1 times compared to control and 1.7 times relative to isolated exposure. At the same time, the level of PGE-2 also decreased in comparison with isolated radiation in 1,1 times. The obtained results indicate the influence of the combined act of irradiation and meloxivet on the level of VEGF and PGE-2, which causes the antiangiogenic effect.Сonclusions. It has been shown that low doses of ionizing radiation (1 Gy) and high doses (10 Gy) have a different effect on VEGF expression, and thus on angiogenesis processes. The combined effect of ionizing radiation and the COX-2 inhibitor (meloxivet) affects the level of PGE-2, VEGF, ie, the slowing of angiogenesis. In the case of large doses of exposure, this effect is even more expressed.

Radiation,induced changes in connective tissue matrix of rat organs at total body X-ray exposure. / Radiacijno-indukovani zminy u spoluchnotkanynnomu matryksi organiv shhuriv za umov zagal''nogo rentgenivs''kogo oprominennja.

Objective. To study the nature of radiation-induced changes in the connective tissue matrix of rats under single total body X-ray exposure in minimal lethal and sublethal doses. Materials and methods. Experiments conducted on white male rats weighing 160-180 g, which were exposed to the influence of X-radiation doses LD15/30 and LD60/30 at the installation RUM-17 in standard specifications. Assessment of connective tissue matrix was performed by the total content of collagen, soluble (SC) and insoluble (ISC) collagen, collagen destruction rate by free hydroxyproline, collagenlytic activity (CLA), individual glycosaminoglycans (GAG). Experiments were performed on days 3, 7 and 14 and 30th, 90th and 180th days. The age control was used to each term of experiments. Statistical analysis of data was performed using Wilcoxon-Mann-Whitney criterion and Student's t-test using packet Biostatistics v.4.03 for Windows. Results. The changes of collagen (3-7 days) were characterized by violation of ratio SC and ISC, accelerated disintegration of collagen by free hydroxyproline in the lungs - 1.7 times, the skin - 1.2 times, rising of metal-depending CLA in the lungs - 2.0 times and metal-independing CLA in the skin - 2.2 times, an increase of hyaluronic acid in the lungs - 1.7 times, in the skin - 1.5 times. At the late period (180 days) an increase of the total content of collagen was determined with a 1.4 times predominance of IC in the lungs and 1.3 times in the skin. During this period changes of individual GAG were characterized by - 1.7 times increase of chondroitin sulfate A and C in the lungs, 1.6 times dermatan sulfate in the skin and 1.7 times heparan sulfate in both organs. Conclusion. Revealed radiation-induced changes in the connective tissue matrix of rats in their direction were not dependent on the dose of X-rays, were organ-specific and determined by time after exposure.

[Effect of subtherapeutic doses of docetaxel (taxotere) on the efficacy of radiotherapy and pro-oxidant-antioxidant balance in rats with Guerin's carcinoma]. / Vliianie subterapevticheskikh doz dotsetaksela (taksotera) na éffektivnost' radioterapii i prooksidantno-antioksidantnyi balans u krys s kartsinomoi Gerena.

In the experiments at Wistar male rats the effect of subtherapeutic doses of docetaxel (5 and 10 mg/kg) on the radiotherapy efficacy (20 Gy of single-dose X-rays) namely growth rate of Guerin's tumor and prooxidant-antioxidant balance in liver and blood of animals bearing tumors was investigated. It has been demonstrated that docetaxel at dose 5 mg/kg given 18 hours before irradiation resulted in significant tumor growth delay (2.3-2.7-fold) in comparison with group of rats that received only irradiation. After application of higher dose of docetaxel there was no statistically significant change of tumor size along the whole experiment (14 and 21 days after tumor implantation). Content of lipid peroxidation products was revealed to be considerably increased after chemotherapy and concurrent irradiation when docetaxel was used in a dose of 10 mg/kg. At the same time glutatione peroxidase activity and antioxidative activity of blood plasma were reduced. In the rat liver chemoradiotherapy led to decrease of glutathion peroxidase and glutathione-S-transferase activity to greater degree at docetaxel dose of 10 mg/kg. The obtained results allow to conclude that higher dose of docetaxel and concurrent irradiation resulted in the most effective Guerin's carcinoma growth delay and considerable deviation of antioxidant-prooxidant balance of tissues in the direction of the last.