RESUMEN
OBJECTIVE: Determination of the peculiarities of ultrastructural changes and metabolism of reactive forms of oxy gen and nitrogen in the tissues of the myocardium, aorta and portal vein of the radiosensitive BALB/c mice due long term exposure to the complex of radionuclides of Chоrnobyl fallout (ejection) and low intensity low dose γ irradiation. MATERIALS AND METHODS: Experimental studies were performed on 60 mice female radiosensitive lines BALB/c with a body weight of 20-22 g, which were divided into 3 groups: I group (control) animals age 6-9 months which were born and lived their lives in Kyiv vivarium under conditions natural radioactive background; ÐÐ - animals age 6 months, which were born and lived in the Chornobyl exclusion zone throughout their lives; ÐÐÐ - animals, which from 3 months of age for 6 months were constantly located in cages with flat ionizing radiation sources and exposed to external γ irradiation in a total dose of 0.43 Sv. Animals of II and III groups were kept in the vivarium of the Institute for Safety Problems of Nuclear Power Plants of the National Academy of Sciences of Ukraine (Chornobyl). Mice of the BALB/c lines are sensitive to radiation: for males LD 50/30 < 5.7 Gy, for females - 5.85 Gy. RESULTS AND CONCLUSIONS: The peculiarities of structural and functional changes in the organs of the cardiovascular system (CVS) and mechanisms of the development of oxidative and nitrosatitative stress due long term exposure to the complex of radionuclides of the Chornobyl fallout (ejection) and low intensity low dose γ radiation based on the study of ultrastructural organization and metabolism of reactive oxygen species (ROS) and nitrogen (NRS) of the atri al cardiomyocytes (CMC), the aortic endothelium and portal vein of the BALB/c mice. Found that the permanent expo sure to low doses of radiation changes occur, including the dominant mechanism is to run a CMC apoptosis and endothelial cells of the aorta and portal vein. It is shown that the development of oxidative stress accompanied by increased activity of ROS metabolism that occurs due to activation of nucleotide and lipid superoxide generators. Found that under these conditions the development of nitrosative stress is due to the activation of inducible NO syn thesis enzyme iNOS and inhibit its synthesis constitutive eNOS enzyme. High levels of simultaneous generation of superoxide and NO, bindting, lead to the formation of toxic peroxynitrite, which initiates the process of apoptosis.
Asunto(s)
Células Endoteliales/efectos de la radiación , Rayos gamma/efectos adversos , Miocitos Cardíacos/efectos de la radiación , Ácido Peroxinitroso/metabolismo , Radioisótopos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Aorta/metabolismo , Aorta/patología , Aorta/efectos de la radiación , Apoptosis/efectos de la radiación , Accidente Nuclear de Chernóbil , Relación Dosis-Respuesta en la Radiación , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de la radiación , Ácido Peroxinitroso/agonistas , Vena Porta/metabolismo , Vena Porta/patología , Vena Porta/efectos de la radiación , Cultivo Primario de Células , Dosis de Radiación , Tolerancia a Radiación , Ceniza Radiactiva/análisis , Especies Reactivas de Oxígeno/agonistas , UcraniaRESUMEN
Peculiarities of changes in the vascular reactivity and in the content of reactive forms of oxygen and stable metabolites of nitric oxide (NO) were studied in the aorta preparations of C57BL/6 and BALB/c mice of the two age groups (6 and 18 mo.), which were born and permanently kept in the Chernobyl alienation zone. The results obtained showed a disturbance of acetylcholine-induced endothelium-dependent reactions of relaxation of smooth muscles of the thoracic aorta. A lower level of NO synthesis and lower level of oxidative arginase metabolism of arginine corresponded to a higher degree of damage of endothelium-dependent reactions of relaxation of the thoracic aorta smooth muscles. A decrease of NO synthesis in conditions of permanent effects of low doses of radiation was conditioned by an increase of generation of reactive forms of oxygen, namely, superoxide and hydroxyl radicals, which might be formed in mitochondria. In conditions of permanent effects of low doses of radiation a lesser level of protein nitrosothilation, same as lesser one of generation of OH-radical, corresponded to a higher level of damage of endothelium-dependent reactions.
Asunto(s)
Aorta Torácica/efectos de la radiación , Accidente Nuclear de Chernóbil , Especies Reactivas de Oxígeno/metabolismo , Vasodilatación/efectos de la radiación , Adaptación Fisiológica/efectos de la radiación , Animales , Aorta Torácica/metabolismo , Relación Dosis-Respuesta en la Radiación , Endotelio Vascular/metabolismo , Endotelio Vascular/efectos de la radiación , Femenino , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de la radiación , Óxido Nítrico/biosíntesis , Especificidad de la Especie , Factores de Tiempo , UcraniaRESUMEN
Two fast migrating, major, multiple molecular forms (MMF) of glucose-6-phosphate dehydrogenase [EC:1.1.1.49]: G-6-PDH-1 and G-6-PDH-2, and two minor forms: G-6-PDH-3 and G-6-PDH-4 were revealed in the electrophoregrams of both erythrocytes haemolisates as well in the homogenates of bone marrow cellular lines of rats at control conditions. Daily 1 cGy irradiation of rats up to a cumulative dose of 20 cGy led to a drop of G-6-PDH total activity and it caused a redistribution of the MMF of the enzyme in bone marrow cellular populations. However, G-6-PDH activity in erythrocytes exceeded the control means in all the experimental terms. The calculation of the local redistribution coefficient (l(G-6-FDH-i)) showed that these changes are mainly determined by the increase of the activity of the isoform G-6-PDH-3. Vitamin D3 administration to rats generated a correction of G-6-PDH activity in all studied cellular populations. Meanwhile, the MMF profiles were characterized by multidirectional rearrangements in the bone marrow erythroid and granulocyte-monocyte cells and in erythrocytes. The specificity of changes in the distribution of the MMF of G-6-PDH in the three studied cellular populations depends on the particularities of their energetic metabolism at irradiation conditions and on the modifying action of the natural adaptogen 1,25-dihydroxicholecalciferol.