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Документ Changes in nitric oxide production and development of oxidative stress in rats heart during prolonged triptorelin-induced central deprivation of luteinizing hormone synthesis(Poltava State Medical University, Poltava, 2022) Voroshilova, T. A.; Shepitko, V. I.; Stetsuk, Ye. V.; Akimov, O. Ye.; Puzyryov, G. S.; Ворошилова, Тетяна Анатоліївна; Шепітько, Володимир Іванович; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Пузирьов, Гай СергійовичCentral deprivation of luteinizing hormone synthesis for 365 days leads to the development of oxidative stress in rat hearts. The peak of oxidative damage to the heart under these conditions happens on the 180th day of the central deprivation of luteinizing hormone synthesis. Production of nitric oxide during central deprivation of luteinizing hormone synthesis undergoes complex changes from an initial decrease of NO-synthase-dependent nitric oxide production on the 30th and 90th day to overproduction of nitric oxide from NO-synthases on the 365th day of the experiment.Документ Extracellular matrix of rat liver under the conditions of combining systemic inflammatory response syndrome and chronic alcohol intoxication(Полтавський державний медичний університет, 2022) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Непорада, Каріне СтепанівнаThe aim of this study was to establish the effect of systemic inflammatory response syndrome on the background of chronic alcohol intoxication on the concentration of oxyproline, glycosaminoglycans and sialic acids in the liver of rats. The study was performed on 24 male Wistar rats. Animals were divided into 4 groups of 6 animals: I – control; II – systemic inflammatory response syndrome group; III – alcoholic hepatitis groupand IV – animals with a combination of systemic inflammatory response syndrome and chronic alcohol intoxication. The concentrations of glycosaminoglycans, heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, free oxyproline and sialic acids were studied in the liver tissue homogenate. The combination of systemic inflammatory response syndromeand chronic alcohol intoxication leads to ncreased intensity of collagenolysis, glycoprotein catabolism and reduced intensity of breakdown of proteoglycans of connective tissue of the liver. However, it changes the ratio of individual fractions of glycosaminoglycans in the direction of reducing тtheconcentration of anti-inflammatory and increasing regenerative.Документ Influence of prolonged central deprivation of testosterone synthesis on production of reactive oxygen and nitrogen species and morphological structure of rat testes(Українська медична стоматологічна академія, 2020) Stetsuk, Ye. V.; Akimov, O. Ye.; Shepitko, V. І.; Goltsev, A. М.; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Шепітько, Володимир Іванович; Гольцев, Анатолій МиколайовичSome testicular diseases require long-term use of testosterone synthesis blockers. It is known that testosterone is a necessary component for the physiological cooperation of cell forms of the stroma and parenchyma of testes. The scientific literature contains a limited amount of data about the effect of long-term deprivation of testosterone synthesis on this cooperation. The aim of our study was to establish the effect of long-term (365 days) inhibition of hypothalamic-pituitary stimulation of spermatogenesis on morphological and biochemical parameters in rat testes. Central deprivation of testosterone synthesis leads to fibrosis with subsequent disruption of the structural organization of the convoluted seminiferous tubules, hemodynamic disorders, endothelial dysfunction, increased density of blood vessel walls and systemic congestion. A decrease in the activity of constitutive NO synthase isoforms plays a major role in the development of structural changes in the testes of rats.Документ Influence of prolonged tripterelin-induced central deprivation of testosterone synthesis on morphological structure of rat’s liver(Українська медична стоматологічна академія, 2021) Polyvyana, O. A.; Shepitko, K. V.; Stetsuk, Ye. V.; Akimov, O. Ye.; Dubinin, D. S.; Полив'яна, Олександра Анатоліївна; Шепітько, Костянтин Володимирович; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Дубінін, Дмитро СергійовичIn recent years, the incidence of prostate cancer has increased worldwide. For example, in 2012, the GLOBOCAN project found that prostate cancer was the second most commonly diagnosed cancer and the fifth leading cause of cancer deaths among men worldwide. Insufficient testosterone can exacerbate liver damage caused by obesity. The aim of our study was to identify morphological changes in the liver of rats at the tissue and cellular levels, to study the processes of formation of reactive oxygen species and the intensity of lipid peroxidation during prolonged central deprivation of testosterone synthesis caused by triptereline. Triptorelin-induced central deprivation of testosterone synthesis leads to oxidative damage to hepatocytes due to increased production of reactive oxygen species and decreased activity of antioxidant enzymes. Oxidative damage to liver cells begins at the molecular and cellular levels and becomes apparent at the tissue level on day 180 of the central deprivation of testosterone synthesis.Документ Influence of transcription factor κB on remodeling of extracellular matrix of rat liver under conditions of chronic alcohol intoxication(Полтавський державний медичний університет, 2022) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Непорада, Каріне СтепанівнаLiver fibrosis is a common tissue reaction associated with chronic liver damage resulting from prolonged parenchymal cell damage and inflammation. The fibrogenic response is characterized by the progressive accumulation of extracellular matrix components enriched in collagen fibrils and impaired extracellular matrix remodeling. The aim of this study was to establish the effect of transcriptional factor κB on the concentration of oxyproline, glycosaminoglycans and sialic acids in the liver of rats under conditions of chronic alcohol intoxication. The study was performed on 24 male Wistar rats. The animals were divided into 4 groups of 6 animals: І – control; II – animals with inhibition of κB; ІІI – animals with chronic alcohol hepatitis and ІV – animals with κB inhibition on the background of chronic alcohol intoxication. We studied the total concentration of glycosaminoglycans, concentration of heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, free oxyproline and sialic acids in the liver tissue homogenate. Prolonged alcohol intoxication of rats leads to remodeling of the extracellular matrix as evidenced by increased collagenolysis and catabolism of glycoconjugates of amorphous connective tissue of the liver. The use of the inhibitor of the transcription factor κB in the background of prolonged alcohol intoxication of animals reduced the concentration of GAG by 1.43 times, lowered oxyproline concentration by 1.6 times and decreased the concentration of sialic acids by 1.14 times compared to chronic alcohol intoxication group. Transcriptional factor NF-κB under conditions of chronic alcohol intoxication affects the architectural remodeling of connective tissue of rat liver by increasing degradation of collagen fibers and destruction of glycoproteins and proteoglycans of the extracellular matrix.Документ Morphofunctional features of rat testes interstitial endocrinocytes and sustentocytes after 90 days of central testosterone synthesis deprivation(Українська медична стоматологічна академія, 2020) Stetsuk, Ye. V.; Akimov, O. Ye.; Shepitko, K. V.; Goltsev, A. N.; Стецук, Євген Валерійович; Стецук, Евгений Валерьевич; Акімов, Олег Євгенович; Акимов, Олег Евгеньевич; Шепітько, Костянтин Володимирович; Шепитько, Константин Владимирович; Гольцев, Анатолій Миколайович; Гольцев, Анатолий НиколаевичWith the social system development, there is a tendency to change attitudes towards family and family values. In developed European countries, there is a trend towards high sexual activity in elderly men and late creation of a family with children, which undergoes certain difficulties in connection with a decreased testosterone production in later years. The purpose of the study was to establish the microscopic organization of rat interstitial endocrinocytes and sustentocytes, to determine the sources of nitric oxide production and the intensity of oxidative stress in the testes with experimental central deprivation of testosterone synthesis with diphereline on the 90th day of the experiment. The experiments were carried out on 20 sexually mature male white rats of the Wistar line. Rats were divided into 2 groups: the control group (10) and the experimental group (10), which were injected subcutaneously with diphereline (Triptorelin embonate) at a dose of 0.3 mg / kg of the active substance for 90 days. Prolonged central deprivation of testosterone synthesis in animals leads to emergence of functional stress structural signs in population of sustentocytes and interstitial endocrinocytes, which are aimed to support testicular secretion. Central deprivation of testosterone synthesis within 90 days causes oxidative stress development owing to reactive oxygen species hyperproduction and nitrite accumulation in testicular tissue due to increased inducible NO-synthase activity;Документ Morphological and functional changes of the hepatic vascular bed Under the conditions of modeling alcoholic hepatitis(Полтавський державний медичний університет, 2021) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Непорада, Каріне СтепанівнаThe experiments were performed on 30 white adult outbred male rats weighing 180–220 g. Animals were divided into 2 groups: I – control (n=6); II – animals with simulated alcoholic hepatitis (n=24). We studied the total NO synthase activity, peroxynitrite, nitrites and nitrosothiols concentrations in rat liver homogenate. We also studied morphometric parameters of hemomicrocirculatory tract of the rat liver. On the 7th day of modeling of alcoholic hepatitis interparticle arteries and veins and lobular arterioles narrow. The central vein dilates. The sinusoidal capillaries around the hepatic triad and central vein dilate. Alcoholic hepatitis increases the total activity of NO synthases, the concentration of peroxynitrites and nitrosothiols, but reduces the concentration of nitrites in the liver of rats on day 7 of the experiment. Nitric oxide and its metabolites play an important role in the regulation of the resistant part of the hemomicrocirculatory tract of the rat liver in the first three days of the experiment. Further redistribution of nitric oxide cycle metabolites leads to an increase in the concentration of peroxynitrite, which is a factor of secondary alteration; Експерименти виконані на 30 білих статевозрілих безпородних щурах-самцях, вагою 180-220 г. Тварини були розділені на 2 групи: І – контрольна (n=6); ІІ група – тварини, яким моделювали алкогольний гепатит (n=24). В гомогенаті печінки щурів визначали активність загальної NO-синтази, концентрації пероксинітриту, нітритів та нітрозотіолів. Також визначали морфометричні параметри емомікроциркуляторного русла печінки щурів. На 7 добу моделювання алкогольного гепатиту міжчасточкові артерії і вени, часточкові артеріоли звужуються. Центральна вена розширюється. Синусоїдні капіляри навколо печінкової тріади і центральної вени розширяються. Алкогольний гепатит збільшує загальну активність NO-синтаз, концентрацію пероксинітритів та нітрозотіолів, проте знижує концентрацію нітритів у печінці щурів на 7 добу експерименту. Оксид азоту і його метаболіти грають важливу роль в регуляції резистентної ланки гемомікроциркуляторного русла печінки щурів перші три доби експерименту, подальший перерозподіл метаболітів циклу оксиду азоту призводить до збільшення концентрації пероксинітриту, який виступає фактором вторинної альтерації.Документ Peculiarities of connective tissue degradation in rat’s liver on early terms of chronic alcoholic hepatitis modelling(Українська медична стоматологічна академія, 2021) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина АнатоліївнаThe article deals with the peculiarities of connective tissue degradation in rat liver on early terms of chronic alcoholic hepatitis modelling. Modeling of chronic alcoholic hepatitis leads to the development of oxidative stress in rat liver tissues due to a decrease in the activity of antioxidant enzymes and an increase in the production of reactive oxygen species. As a result of the development of oxidative stress in the liver of rats in the first stages of modeling alcoholic hepatitis, the concentration of the anti-inflammatory heparin-heparan fraction of glycosaminoglycans decreases, the accumulation of keratan-dermatan and chondroitin fractions of glycosaminoglycans occurs. The processes of degradation of the fibrous components of the liver’s connective tissue increase and the concentration of the sulfide anion decreases.Документ Role of nitric oxide in development of fibrotic changes in rats’ testes after 270 day central deprivation of testosterone synthesis(Українська медична стоматологічна академія, 2020) Stetsuk, Ye. V.; Akimov, O. Ye.; Shepitko, K. V.; Boruta, N. V.; Goltsev, A. M.; Стецук, Евгений Валерьевич; Акимов, Олег Евгеньевич; Шепитько, Константин Владимирович; Борута, Наталия Владимировна; Гольцев, Анатолий Николаевич; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Шепітько, Костянтин Володимирович; Борута, Наталія Володимирівна; Гольцев, Анатолій МиколайовичDisturbance in production of nitric oxide (NO) may lead to various changes in different organs and systems. Certain clinical situations require prolonged usage of inhibitors of testosterone synthesis. Scientific literature provides limited information regarding the influence of prolonged deprivation of testosterone synthesis on production of NO and microscopic organization of rats’ testes. Prolonged central deprivation of testosterone synthesis leads to endothelial dysfunction, development of fibrosis, decreases the nitric oxide production and shifts pro-/antioxidant balance in favor of the pro-oxidants without increase in lipid peroxidation intensity. Central deprivation of testosterone synthesis leads to fibrosis with subsequent disruption of the structural organization of the convoluted seminiferous tubules, hemodynamic disturbances, endothelial dysfunction, increased density of the vascular wall of blood vessels and systemic stasis. Decreased production of NO from constitutive isoforms of NO-synthase plays major role in development of structural changes in the interstitial tissue of testes on the 270th day of the experiment.Документ Structural organization of stromal and parenchymal components of rat testes during central deprivation of testosterone synthesis on the 180 day of the experiment(Українська медична стоматологічна академія, 2020) Стецук, Євген Валерійович; Стецук, Евгений Валерьевич; Stetsuk, Ye. V.; Акімов, Олег Євгенович; Акимов, Олег Евгеньевич; Akimov, O. Ye.; Шепітько, Костянтин Володимирович; Шепитько, Константин Владимирович; Shepitko, K. V.; Гольцев, Анатолій Миколайович; Гольцев, Анатолий Николаевич; Goltsev, A. M.Prolonged central deprivation of testosterone synthesis may lead to biochemical and morphological changes in testes. Influence of prolonged testosterone deficiency on reactive nitrogen and oxygen species production, morphological changes in interstitial endocrinocytes and sustentocytes is not yet fully understood. The number of interstitial endocrinocytes is reduced in comparison with the control group, there are interstitial spaces between the convoluted tubules with a complete absence of interstitial endocrinocytes. Interstitial endocrinocytes are reduced in size, their nuclei are heterochromic. When we studied the structural organization of rat sustentocytes from the experimental group in comparison with the control group, we found that hyperplasia of the elements of the smooth endoplasmic reticulum was observed in the cytoplasm of the sustentocytes. The number of mitochondria in the cytoplasm of the sustentocytes decreased, the electron density of the mitochondrial matrix was lowered, protein structures were present either inside the vacuoles or independently located in the cell cytoplasm. Biochemical studies revealed increased NO production from inducible NO-synthase and development of oxidative stress. Experimental central deprivation of testosterone synthesis with diphereline on the 180th day of the experiment leads to shift of NO synthesis from constitutive NO-synthases to inducible NO-synthase and intensification of oxidative stress due to increase of superoxide anion-radical production and decrease in antioxidant protection.Документ The reaction of immunocompetent liver cells during chemical castration of male rats caused by the introduction of triptorelin acetate(Полтавський державний медичний університет, 2021) Rud, M. V.; Shepitko, V. I.; Stetsuk, Ye. V.; Akimov, O. Ye.; Vilkhova, O. V.; Skotarenko, T. A.; Рудь, Марія Володимирівна; Шепітько, Володимир Іванович; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Вільхова, Олена Вікторівна; Скотаренко, Тетяна АнатоліївнаThe purpose of our study was to elucidate the qualitative and quantitative changes in immunocompetent liver cells during chemical castration of male rats of central origin caused by the introduction of triptorelin acetate solution at different time intervals, to determine the sources of nitric oxide production as well as the effects of quercetin on morphological and quantitative changes of antigenpresenting liver cells. The morphological changes in the experimental groups with central testosterone deprivation and with its subsequent correction with quercetin on the 30th day of the experiment are identical and include signs of stromal ‒ vascular changes in the form of an increase in the thickness of the beam system and minor venous stasis with macrophage infiltration. Central 30 ‒ day deprivation of testosterone synthesis leads to a shift in the functioning of enzymes of the nitric oxide cycle in rat liver towards a predominance of the activity of inducible NO-synthase.