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INFLUENCE OF COMBINED ACTION OF X-RADIATION AND CYCLOOXYGENASE-2 – MELOXIVET INHIBITOR ON VEGF AND PGE-2 CONTENT IN BLOOD OF RAT-TUMOR CARRIERS

2019; Volume: 24; Linguagem: Inglês

10.33145/2304-8336-2019-24-261-269

2313-4607

N. A. Mitryayeva, L.V. Grebinyk, Nataliya Uzlenkova,

Estrogen and related hormone effects

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.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 «Meloxivet» - 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.Meta: vyvchennia vplyvu kombinovanoï diï Kh-vyprominennia ta ingibitora tsyklooksygenazy-2 (TsOG-2) na riven' faktora rostu endoteliiu sudyn (VEGF) i prostaglandynu E-2 (PGE-2)-2 v syrovattsi krovi shchuriv z perevytoiu pukh- lynoiu Gerena pry oprominenni v riznykh dozakh.Materialy i metody. 20 shchuram-samytsiam populiatsiï Vistar masoiu 160–180 g z pereshcheplenoiu kartsynomoiu Gere- na provodyly fraktsionovane oprominennia (5 Gr + 5 Gr) ta (0,5 Gr + 0,5 Gr) zony rostu pukhlyny na aparati RUM-17 z intervalom mizh seansamy 24 god. Preparat «Meloksyvet» – selektyvnyy̆ ingibitor TsOG-2 vvodyly za dobu do oprominennia ta za 2 godyny pered drugym oprominenniam (0,2 mg na 1kg masy tila). Zabir krovi provodyly meto- dom pryzhyttievoï dekapitatsiï cherez 24 god pislia ostann'oï fraktsiï oprominennia. Vmist VEGF ta PGE-2 v syrovattsi krovi vyznachaly metodom imunofermentnogo analizu z vykorystanniam standartnykh naboriv.Rezul'taty. Pislia fraktsionovanogo oprominennia u sumarniy̆ dozi 1 Gr (0,5 Gr + 0,5 Gr) riven' VEGF pidvyshchuvav- sia u 1,5 raza porivniano z intaktnym kontrolem, a u tvaryn, oprominenykh u sumarniy̆ dozi 10 Gr (5 Gr + 5 Gr), riven' VEGF virogidno znyzhuvavsia u 1,92 raza. Tobto, sposterigaly riznytsiu vmistu VEGF v syrovattsi krovi shchuriv-pukhly- nonosiïv zalezhno vid doz oprominennia: pislia oprominennia sumarniy̆ dozi 1 Gr – stymuliatsiia angiogenezu, 10 Gr – znachne upovil'nennia ts'ogo protsesu. U razi poiednanoï diï oprominennia (10 Gr) ta ingibitora TsOG-2 – meloksyve- tu vidmichaly virogidne znyzhennia rivnia VEGF u 3,49 raza porivniano z kontrolem ta u 1,8 raza z izol'ovanym op- rominenniam. Pry ts'omu riven' PGE-2 takozh znyzhuvavsia vidnosno izol'ovanogo oprominennia u 1,5 raza, shcho vka- zuie na ingibuvannia TsOG-2. Pry poiednaniy̆ diï oprominennia v nyz'kykh dozakh (1 Gr) ta ingibitora TsOG-2 – meloksy- vetu sposterigaly znyzhennia rivnia VEGF u 1,1 raza porivniano z kontrolem ta u 1,7 raza vidnosno izol'ovanogo op- rominennia. Pry ts'omu riven' PGE-2 takozh znyzhuvavsia porivniano z izol'ovanym oprominenniam u 1,1 raza. Otry- mani rezul'taty svidchat' pro vplyv poiednanoï diï oprominennia i meloksyvetu na riven' VEGF ta PGE -2, shcho zumov- liuie antyangiogennyy̆ efekt.Vysnovky. Dovedeno, shcho nyz'ki dozy ionizuiuchoï radiatsiï (1 Gr) ta vysoki dozy (10 Gr) po-riznomu vplyvaiut' na ekspresiiu VEGF, i tym samym na protsesy angiogenezu. Poiednana diia ionizuiuchoï radiatsiï ta ingibitora TsOG-2 (me- loksyvetu) vplyvaie na znyzhennia rivnia PGE-2, VEGF, tobto, na upovil'nennia angiogenezu. U razi velykykh doz op- rominennia tsey̆ vplyv vyrazhenyy̆ shche bil'she.