O. Podkovka, M. Makarchuk, N. Filimonova, I. Pampuha, Ye.V. Varzhanska
Operators are often subjected to a high working memory load as far as any possibly useful information must always be available and presented to the operator. Thus, we assumed that they may have developed adaptations in mechanisms of working memory realization that help them to be more efficient in information overload conditions. Our aim was to define differences in visual working memory functioning in radar station operators (RSO) and other military profession representatives. For this purpose, in parallel with the performance of original computer tests for the visual working memory identification, which had two levels of complexity, we recorded an electroencephalogram with subsequent coherent and LORETA analysis and electrocardiogram with subsequent determining of stress index of the regulatory systems. It was found that reaction time, as well as the number of errors in both tests, didn`t differ significantly for the two groups. At the same time, the control group had a significantly higher number of θ-band coherent connections in the frontal lobe in both tests, which could indicate a higher level of mental stress and emotional involvement. This assumption was confirmed by the stress index dynamic in the control group. LORETA analysis showed that in the RSO group, the degree of fronto-parietal, cingulo-opercular networks, cuneus and precuneus involvement was at a high level from the very first tasks, while in the control group, it increased with task complexity, that is the evidence of adaptive changes in the working memory of RSO, due to which they successfully cope with information overload.
{"title":"NEUROBIOLOGICAL AND PSYCHOPHYSIOLOGICAL DIFFERENCES OF VISUAL WORKING MEMORY FUNCTIONING IN RADAR STATION OPERATORS","authors":"O. Podkovka, M. Makarchuk, N. Filimonova, I. Pampuha, Ye.V. Varzhanska","doi":"10.15407/fz69.06.022","DOIUrl":"https://doi.org/10.15407/fz69.06.022","url":null,"abstract":"Operators are often subjected to a high working memory load as far as any possibly useful information must always be available and presented to the operator. Thus, we assumed that they may have developed adaptations in mechanisms of working memory realization that help them to be more efficient in information overload conditions. Our aim was to define differences in visual working memory functioning in radar station operators (RSO) and other military profession representatives. For this purpose, in parallel with the performance of original computer tests for the visual working memory identification, which had two levels of complexity, we recorded an electroencephalogram with subsequent coherent and LORETA analysis and electrocardiogram with subsequent determining of stress index of the regulatory systems. It was found that reaction time, as well as the number of errors in both tests, didn`t differ significantly for the two groups. At the same time, the control group had a significantly higher number of θ-band coherent connections in the frontal lobe in both tests, which could indicate a higher level of mental stress and emotional involvement. This assumption was confirmed by the stress index dynamic in the control group. LORETA analysis showed that in the RSO group, the degree of fronto-parietal, cingulo-opercular networks, cuneus and precuneus involvement was at a high level from the very first tasks, while in the control group, it increased with task complexity, that is the evidence of adaptive changes in the working memory of RSO, due to which they successfully cope with information overload.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139281343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M.V. Denysova, N. Strutynska, L. A. Mys, Yu.P. Korkach, K. Rozova, V. F. Sagach
Doxorubicin is a potent cytotoxic antibiotic that is the most widely prescribed in the world and is effective against a wide range of cancers. At the same time, the cardiotoxic effects of this drug often require discontinuation of treatment before the effect is achieved. Mitochondria are important mediators of cellular life, and cardiomyocyte death due to mitochondrial mechanisms of internal killing is the basis of many heart diseases. The aim of the study was to investigate the effects of short-term doxorubicin administration on Ca2+-induced opening of the nonspecific mitochondrial permeability transition pore (mPTP) in the heart of adult rats. To reproduce and evaluate acute cardiotoxicity in rats, which is the main complication in patients taking doxorubicin, a short-term doxorubicin cardiomyopathy model was used. A comparative ultrastructural study of myocardial tissues was performed at total cumulative doses of doxorubicin of 8, 13 and 15 mg/kg administered intraperitoneally and spread over two days. It was shown that the drug caused damage and death of the myofibrillar apparatus, mitochondria and cardiomyocytes and exhibited a dose-dependent effect. Therefore, further experiments were carried out at the most indicative dose, namely 15 mg/kg. We have shown that the content of reactive oxygen species in the heart mitochondria, namely, •O2-, Н2О2, •ОН, increased after doxorubicin administration by 10.5, 5.3 and 3.4 times, respectively, indicating a significant increase in free radical processes. It is important that at the same time, the content of endogenous H2S decreased by 2.6 times. This activated mPTP opening in the rat heart: the amplitude of spontaneous swelling doubled, Ca2+-induced swelling increased by 53% compared to the control, and an increase in mPTP sensitivity to Ca2+ was observed at all applied concentrations. Thus, the acute cardiotoxic effect of doxorubicin resulted in the induction of mPTP opening, which led to mitochondrial and cardiomyocyte death.
{"title":"MITOCHONDRIAL DYSFUNCTION IN ACUTE CARDIOTOXIC EFFECT OF DOXORUBICIN IN ADULT RATS","authors":"M.V. Denysova, N. Strutynska, L. A. Mys, Yu.P. Korkach, K. Rozova, V. F. Sagach","doi":"10.15407/fz69.06.003","DOIUrl":"https://doi.org/10.15407/fz69.06.003","url":null,"abstract":"Doxorubicin is a potent cytotoxic antibiotic that is the most widely prescribed in the world and is effective against a wide range of cancers. At the same time, the cardiotoxic effects of this drug often require discontinuation of treatment before the effect is achieved. Mitochondria are important mediators of cellular life, and cardiomyocyte death due to mitochondrial mechanisms of internal killing is the basis of many heart diseases. The aim of the study was to investigate the effects of short-term doxorubicin administration on Ca2+-induced opening of the nonspecific mitochondrial permeability transition pore (mPTP) in the heart of adult rats. To reproduce and evaluate acute cardiotoxicity in rats, which is the main complication in patients taking doxorubicin, a short-term doxorubicin cardiomyopathy model was used. A comparative ultrastructural study of myocardial tissues was performed at total cumulative doses of doxorubicin of 8, 13 and 15 mg/kg administered intraperitoneally and spread over two days. It was shown that the drug caused damage and death of the myofibrillar apparatus, mitochondria and cardiomyocytes and exhibited a dose-dependent effect. Therefore, further experiments were carried out at the most indicative dose, namely 15 mg/kg. We have shown that the content of reactive oxygen species in the heart mitochondria, namely, •O2-, Н2О2, •ОН, increased after doxorubicin administration by 10.5, 5.3 and 3.4 times, respectively, indicating a significant increase in free radical processes. It is important that at the same time, the content of endogenous H2S decreased by 2.6 times. This activated mPTP opening in the rat heart: the amplitude of spontaneous swelling doubled, Ca2+-induced swelling increased by 53% compared to the control, and an increase in mPTP sensitivity to Ca2+ was observed at all applied concentrations. Thus, the acute cardiotoxic effect of doxorubicin resulted in the induction of mPTP opening, which led to mitochondrial and cardiomyocyte death.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139280863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. Kondratska, N. Grushka, V.V. Veshko, S. Pavlovych, R. Yanchii
The review summarizes generalizing modern scientific data on the main functions of the protein HMGB1, and its physiological and pathological roles. Amphoterin is involved in key processes that ensure the functioning of DNA in the cell nucleus and plays an important role outside it. HMGB1 has been implicated in many human inflammatory diseases such as sepsis, ischemic reperfusion injury, neurological conditions, cardiovascular disease, autoimmune disease, and others. This manuscript describes the structure and main functions of HMGB1, discusses the significance of this alarmin as damage-associated molecular patterns, and analyzes its role in the development of inflammation and cell death. Special attention is focused on the role of HMGB1 in the development of endotoxemia, as well as data on the signaling pathways involved in its pathogenesis. Information on the results of studies of the possibility of modulating the activity of this protein using inhibitors is also considered, since understanding this may be useful for developing new therapeutic strategies aimed at treating inflammatory conditions of various origins.
这篇综述概述了有关蛋白质 HMGB1 的主要功能及其生理和病理作用的现代科学数据。两性霉素参与了确保 DNA 在细胞核内运行的关键过程，并在细胞核外发挥着重要作用。HMGB1 与败血症、缺血再灌注损伤、神经系统疾病、心血管疾病、自身免疫性疾病等多种人类炎症性疾病有关。本手稿描述了 HMGB1 的结构和主要功能，讨论了这种警报蛋白作为损伤相关分子模式的意义，并分析了它在炎症发展和细胞死亡中的作用。文章特别关注了 HMGB1 在内毒素血症发展过程中的作用，以及有关其发病机制信号通路的数据。此外，还考虑了有关使用抑制剂调节该蛋白活性的可能性的研究结果信息，因为了解这一点可能有助于开发旨在治疗各种炎症的新疗法。
{"title":"MULTIFUNCTIONAL ACTIVITY OF NUCLEAR PROTEIN AMPHOTERIN AND ITS ROLE IN ENDOTOXEMIA","authors":"O. Kondratska, N. Grushka, V.V. Veshko, S. Pavlovych, R. Yanchii","doi":"10.15407/fz69.06.120","DOIUrl":"https://doi.org/10.15407/fz69.06.120","url":null,"abstract":"The review summarizes generalizing modern scientific data on the main functions of the protein HMGB1, and its physiological and pathological roles. Amphoterin is involved in key processes that ensure the functioning of DNA in the cell nucleus and plays an important role outside it. HMGB1 has been implicated in many human inflammatory diseases such as sepsis, ischemic reperfusion injury, neurological conditions, cardiovascular disease, autoimmune disease, and others. This manuscript describes the structure and main functions of HMGB1, discusses the significance of this alarmin as damage-associated molecular patterns, and analyzes its role in the development of inflammation and cell death. Special attention is focused on the role of HMGB1 in the development of endotoxemia, as well as data on the signaling pathways involved in its pathogenesis. Information on the results of studies of the possibility of modulating the activity of this protein using inhibitors is also considered, since understanding this may be useful for developing new therapeutic strategies aimed at treating inflammatory conditions of various origins.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139281307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Shtanova, S. P. Vesеlsky, P. Yanchuk, O. Tsymbalyuk, O.F. Moroz, E. Reshetnik, V. Moskvina, O. Shablykina, О.V. Kravchenko, V. Khilya
Parkinson’s disease (PD) is a neurodegenerative condition for which the exact causes remain elusive, and no effective treatments currently exist. The pathogenesis of PD is believed to involve oxidative stress, mitochondrial dysfunction, and lipid metabolism disorders. A benzodiazepine derivative JM-20 has demonstrated protective effects on mitochondria in both neurons and peripheral tissues of rats with rotenoneinduced Parkinson’s syndrome (PS). This study aimed to analyze bile composition and assess the impact of a new benzodiazepine derivative, methanindiazenone, on lipid metabolism in the liver of rats subjected to the rotenone model of PS. The results indicated that, compared to the control group, bile concentration of phospholipids, cholesterol, cholesterol esters, and triglycerides decreased by 24.3, 26.2, 25.8, and 27.5%, respectively. With methanindiazenone treatment at doses of 0.5 and 1.0 mg/kg, all these metrics reverted to the control level. However, in the rotenone+methanindiazenone 2.0 mg/kg group, the levels of phospholipids, cholesterol, and cholesterol esters (except for triglycerides) surpassed the control values by 33, 28.1, 28.4 and 33.5%, respectively. Methanindiazenone positively impacted the motor behavior of rats with the rotenone model of PS and enhanced their survival rates. Therefore, at doses of 0.5 and 1.0 mg/kg, methanindiazenone not only improved lipid metabolism in the liver but also the overall well-being of rats with the rotenone model of PS. However, a 2 mg/kg dose of methanindiazenone displayed toxic effects, as seen from the increased content of phospholipids, cholesterol, and cholesterol esters in bile. Hence, methanindiazenone holds potential as a therapeutic agent for PS and possibly other neurodegenerative diseases related to lipid metabolism impairment, but its use should be limited to doses of 0.5 and 1.0 mg/kg.
{"title":"Benzodiazepinе derivative methanindiazenone modulates lipid metabolism in the liver of rats with rotenone-induced Parkinson’s syndrome","authors":"L. Shtanova, S. P. Vesеlsky, P. Yanchuk, O. Tsymbalyuk, O.F. Moroz, E. Reshetnik, V. Moskvina, O. Shablykina, О.V. Kravchenko, V. Khilya","doi":"10.15407/fz69.06.077","DOIUrl":"https://doi.org/10.15407/fz69.06.077","url":null,"abstract":"Parkinson’s disease (PD) is a neurodegenerative condition for which the exact causes remain elusive, and no effective treatments currently exist. The pathogenesis of PD is believed to involve oxidative stress, mitochondrial dysfunction, and lipid metabolism disorders. A benzodiazepine derivative JM-20 has demonstrated protective effects on mitochondria in both neurons and peripheral tissues of rats with rotenoneinduced Parkinson’s syndrome (PS). This study aimed to analyze bile composition and assess the impact of a new benzodiazepine derivative, methanindiazenone, on lipid metabolism in the liver of rats subjected to the rotenone model of PS. The results indicated that, compared to the control group, bile concentration of phospholipids, cholesterol, cholesterol esters, and triglycerides decreased by 24.3, 26.2, 25.8, and 27.5%, respectively. With methanindiazenone treatment at doses of 0.5 and 1.0 mg/kg, all these metrics reverted to the control level. However, in the rotenone+methanindiazenone 2.0 mg/kg group, the levels of phospholipids, cholesterol, and cholesterol esters (except for triglycerides) surpassed the control values by 33, 28.1, 28.4 and 33.5%, respectively. Methanindiazenone positively impacted the motor behavior of rats with the rotenone model of PS and enhanced their survival rates. Therefore, at doses of 0.5 and 1.0 mg/kg, methanindiazenone not only improved lipid metabolism in the liver but also the overall well-being of rats with the rotenone model of PS. However, a 2 mg/kg dose of methanindiazenone displayed toxic effects, as seen from the increased content of phospholipids, cholesterol, and cholesterol esters in bile. Hence, methanindiazenone holds potential as a therapeutic agent for PS and possibly other neurodegenerative diseases related to lipid metabolism impairment, but its use should be limited to doses of 0.5 and 1.0 mg/kg.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139281078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. O. Zavhorodnii, V. Nosar, O.O. Gonchar, P. Tsapenko, M. Kozlovska, M. Vasylenko, V. Portnichenko, A. Portnychenko
Mitochondria are central organelles in maintaining energy and oxidative homeostasis. Despite intensive research, the function of mitochondria and the mechanisms of its regulation under physiological conditions and in insulin resistance require detailed investigation. The aim of this study was to investigate the effect of blockade L-type calcium channels in insulin-resistant rats on hepatic mitochondrial oxidative function and changes in its oxidative status. Insulin resistance was modeled in 6-month-old male Wistar rats by 14 days of high-fat feeding. Standard fed animals served as controls. Verapamil was administered intraperitoneally at a dose of 1 mg/kg to block L-type calcium channels. Indicators of pro- and antioxidant systems (active products of tiobarbituric acid, reduced glutathione, catalase, Cu,Zn-superoxide dismutase) were assayed in the liver homogenate extracted from anesthetized animals after 3 h. Mitochondrial function was studied by the Chance polarographic method using different metabolic substrates. It was shown that in intact animals blockade of L-type calcium channels reduced the efficiency of mitochondrial respiration (V3/V4) in liver mitochondria during oxidation of all substrates through an inhibitory effect on the phosphorylation respiration (V3) and a stimulatory effect on the controlled respiration (V4), without affecting the oxidative status of the liver. In rats with insulin resistance the rate of V3 during oxidation of both NAD- and FADdependent substrates was decreased, violations of oxidative status and increased antioxidant protection were detected. However, in insulin-resistant rats blockade of L-type calcium channels significantly enhanced basic respiration (V2) during NAD-dependent substrate oxidation, V3 and V4 during palmitoyl lipid substrate oxidation, reduced the V3/V4 ratio compared to control, and partially or fully restored the violation of the oxidative status. This may indicate the involvement of calcium mechanisms in the disturbance of the oxidative status of the liver and the regulation of energy metabolism in mitochondria during insulin resistance.
线粒体是维持能量和氧化平衡的核心细胞器。尽管研究深入，但线粒体的功能及其在生理条件下和胰岛素抵抗时的调控机制仍有待详细研究。本研究旨在探讨阻断胰岛素抵抗大鼠的 L 型钙通道对肝线粒体氧化功能及其氧化状态变化的影响。对 6 个月大的雄性 Wistar 大鼠进行为期 14 天的高脂喂养，以建立胰岛素抵抗模型。标准喂养动物作为对照组。腹腔注射维拉帕米，剂量为 1 毫克/千克，以阻断 L 型钙通道。3 小时后，在麻醉动物提取的肝脏匀浆中检测促氧化和抗氧化系统指标（刁巴比妥酸活性产物、还原型谷胱甘肽、过氧化氢酶、铜锌超氧化物歧化酶）。结果表明，在完整的动物体内，通过抑制磷酸化呼吸（V3）和刺激受控呼吸（V4），阻断 L 型钙通道会降低肝脏线粒体在氧化所有底物时的线粒体呼吸效率（V3/V4），而不会影响肝脏的氧化状态。在胰岛素抵抗的大鼠体内，依赖 NAD 和 FAD 的底物氧化过程中的 V3 速率降低，氧化状态受到破坏，抗氧化保护作用增强。然而，与对照组相比，在胰岛素抵抗大鼠体内阻断 L 型钙通道可显著增强 NAD 依赖性底物氧化过程中的基础呼吸（V2）、棕榈酰脂质底物氧化过程中的 V3 和 V4，降低 V3/V4 比率，并部分或完全恢复氧化状态的改变。这可能表明钙机制参与了胰岛素抵抗时肝脏氧化状态的紊乱和线粒体能量代谢的调节。
{"title":"Blockade of L-type calcium channels alters hepatic mitochondrial function in insulin-resistant rats","authors":"M. O. Zavhorodnii, V. Nosar, O.O. Gonchar, P. Tsapenko, M. Kozlovska, M. Vasylenko, V. Portnichenko, A. Portnychenko","doi":"10.15407/fz69.06.088","DOIUrl":"https://doi.org/10.15407/fz69.06.088","url":null,"abstract":"Mitochondria are central organelles in maintaining energy and oxidative homeostasis. Despite intensive research, the function of mitochondria and the mechanisms of its regulation under physiological conditions and in insulin resistance require detailed investigation. The aim of this study was to investigate the effect of blockade L-type calcium channels in insulin-resistant rats on hepatic mitochondrial oxidative function and changes in its oxidative status. Insulin resistance was modeled in 6-month-old male Wistar rats by 14 days of high-fat feeding. Standard fed animals served as controls. Verapamil was administered intraperitoneally at a dose of 1 mg/kg to block L-type calcium channels. Indicators of pro- and antioxidant systems (active products of tiobarbituric acid, reduced glutathione, catalase, Cu,Zn-superoxide dismutase) were assayed in the liver homogenate extracted from anesthetized animals after 3 h. Mitochondrial function was studied by the Chance polarographic method using different metabolic substrates. It was shown that in intact animals blockade of L-type calcium channels reduced the efficiency of mitochondrial respiration (V3/V4) in liver mitochondria during oxidation of all substrates through an inhibitory effect on the phosphorylation respiration (V3) and a stimulatory effect on the controlled respiration (V4), without affecting the oxidative status of the liver. In rats with insulin resistance the rate of V3 during oxidation of both NAD- and FADdependent substrates was decreased, violations of oxidative status and increased antioxidant protection were detected. However, in insulin-resistant rats blockade of L-type calcium channels significantly enhanced basic respiration (V2) during NAD-dependent substrate oxidation, V3 and V4 during palmitoyl lipid substrate oxidation, reduced the V3/V4 ratio compared to control, and partially or fully restored the violation of the oxidative status. This may indicate the involvement of calcium mechanisms in the disturbance of the oxidative status of the liver and the regulation of energy metabolism in mitochondria during insulin resistance.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139281650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Hrytsevych, N.S. Nikitina, L. I. Stepanova, O.M. Savchuk, V. Vereshchaka
Minor injuries in healthy people usually heal well, but larger wounds or the presence of various physiological (age) or pathological conditions (metabolic syndrome, obesity, diabetes, and cancer) can impede this process. The aim of our work was to determine the factors that may influence the duration of healing (growth factors and hypoxia-induced factor 1α) in the wound bed of rats with metabolic syndrome. The experiments were conducted on 80 white non-linear laboratory rats, aged 4-5 months, which were divided after birth into 2 groups of 40 animals each (20 males and 20 females). Group I rats were subcutaneously injected with saline at a dose of 8 μg/ ml on days 2, 4, 6, 8, and 10 after birth. Group II rats were administered a sodium glutamate solution at a dose of 4.0 mg/ kg at the same time. At the age of 4 months, animals of both subgroups were modeled with incised wounds . The control animals were rats in each of the groups in which wounds were not modeled. The material for biochemical studies was the skin in the areas of the former wound bed. Rats in the control group had their skin excised at the same sites as those in the experimental groups. The skin was homogenized and the content of growth factors of endothelial and nerve cells (VEGF, NGF, respectively) and hypoxia-inducible factor (HIF-1α) was determined by immuno-enzymatic method. In unoperated male rats with metabolic syndrome, the skin content of VEGF, NGF, and HIF-1a increased compared to control animals without the syndrome. In unoperated females with metabolic syndrome, VEGF levels decreased with a simultaneous increase in NGF and HIF-1α. In the wound bed of animals with metabolic syndrome, after the closure of the wound surface, the content of VEGF and HIF-1α increased, and the content of NGF remained unchanged compared with the values in unoperated rats. The results obtained indicate the involvement of growth factors VEGF and NGF and HIF-1α in prolonging the duration of healing of incised wounds in rats with metabolic syndrome. At the same time, these growth factors and HIF-1α may be involved in the mechanisms of development of some postoperative complications.
{"title":"CONTENT OF GROWTH FACTORS AND HYPOXIA-INDUCIBLE FACTOR 1Α IN THE WOUND BED OF THE SKIN OF RATS WITH METABOLIC SYNDROME","authors":"N. Hrytsevych, N.S. Nikitina, L. I. Stepanova, O.M. Savchuk, V. Vereshchaka","doi":"10.15407/fz69.06.069","DOIUrl":"https://doi.org/10.15407/fz69.06.069","url":null,"abstract":"Minor injuries in healthy people usually heal well, but larger wounds or the presence of various physiological (age) or pathological conditions (metabolic syndrome, obesity, diabetes, and cancer) can impede this process. The aim of our work was to determine the factors that may influence the duration of healing (growth factors and hypoxia-induced factor 1α) in the wound bed of rats with metabolic syndrome. The experiments were conducted on 80 white non-linear laboratory rats, aged 4-5 months, which were divided after birth into 2 groups of 40 animals each (20 males and 20 females). Group I rats were subcutaneously injected with saline at a dose of 8 μg/ ml on days 2, 4, 6, 8, and 10 after birth. Group II rats were administered a sodium glutamate solution at a dose of 4.0 mg/ kg at the same time. At the age of 4 months, animals of both subgroups were modeled with incised wounds . The control animals were rats in each of the groups in which wounds were not modeled. The material for biochemical studies was the skin in the areas of the former wound bed. Rats in the control group had their skin excised at the same sites as those in the experimental groups. The skin was homogenized and the content of growth factors of endothelial and nerve cells (VEGF, NGF, respectively) and hypoxia-inducible factor (HIF-1α) was determined by immuno-enzymatic method. In unoperated male rats with metabolic syndrome, the skin content of VEGF, NGF, and HIF-1a increased compared to control animals without the syndrome. In unoperated females with metabolic syndrome, VEGF levels decreased with a simultaneous increase in NGF and HIF-1α. In the wound bed of animals with metabolic syndrome, after the closure of the wound surface, the content of VEGF and HIF-1α increased, and the content of NGF remained unchanged compared with the values in unoperated rats. The results obtained indicate the involvement of growth factors VEGF and NGF and HIF-1α in prolonging the duration of healing of incised wounds in rats with metabolic syndrome. At the same time, these growth factors and HIF-1α may be involved in the mechanisms of development of some postoperative complications.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"63 4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139280861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic retinopathy is a progressive tissue-specific neurovascular complication of diabetes with a multifactorial pathogenesis, in which microvascular disorders are preceded by damage to nerve elements. The latter begin with the early involvement of glia, including astrocytes and Müller cells. Taking into account the establishment of GABA-ergic deficiency, the use of modulators of the GABA-benzodiazepine receptor complex, for example, Carbacetam, which has shown satisfactory neuroprotective properties, seems promising. Diabetes mellitus was modeled by a single administration of streptozotocin (50 mg/kg; “Sigma-Aldrich”, China) to threemonth-old male Wistar rats. Already after 7 days, according to immunohistochemical detection of glial fibrillary acidic protein (GFAP), reactive gliosis of astrocytes of the inner retina layers was detected, to which Müller cells joined from the 14th day. The content of GFAP in retinal tissues increased significantly. GFAP-positive cells were in close contact with foci of pathological angiogenesis in the inner layers of the retina and also took part in the formation of fibrous proliferates in the outer layers. Detection of caspase-3 showed the activation of apoptosis in astrocytes and radial processes of Müller cells in the inner plexiform layer. Carbacetam in combination with insulin reduced the expression of GFAP and caspase-3 in the retina and prevented the development of reactive gliosis, angiogenesis, and the formation of fibrous proliferates, which makes it a candidate for further studies in the treatment of diabetic retinopathy.
{"title":"THE INFLUENCE OF A BENZODIAZEPINE RECEPTOR AGONIST ON THE STATE OF GLIA IN THE DIABETIC RETINOPATHY","authors":"S.V. Ziablitzev, D. Zhupan, O. Dyadyk","doi":"10.15407/fz69.06.033","DOIUrl":"https://doi.org/10.15407/fz69.06.033","url":null,"abstract":"Diabetic retinopathy is a progressive tissue-specific neurovascular complication of diabetes with a multifactorial pathogenesis, in which microvascular disorders are preceded by damage to nerve elements. The latter begin with the early involvement of glia, including astrocytes and Müller cells. Taking into account the establishment of GABA-ergic deficiency, the use of modulators of the GABA-benzodiazepine receptor complex, for example, Carbacetam, which has shown satisfactory neuroprotective properties, seems promising. Diabetes mellitus was modeled by a single administration of streptozotocin (50 mg/kg; “Sigma-Aldrich”, China) to threemonth-old male Wistar rats. Already after 7 days, according to immunohistochemical detection of glial fibrillary acidic protein (GFAP), reactive gliosis of astrocytes of the inner retina layers was detected, to which Müller cells joined from the 14th day. The content of GFAP in retinal tissues increased significantly. GFAP-positive cells were in close contact with foci of pathological angiogenesis in the inner layers of the retina and also took part in the formation of fibrous proliferates in the outer layers. Detection of caspase-3 showed the activation of apoptosis in astrocytes and radial processes of Müller cells in the inner plexiform layer. Carbacetam in combination with insulin reduced the expression of GFAP and caspase-3 in the retina and prevented the development of reactive gliosis, angiogenesis, and the formation of fibrous proliferates, which makes it a candidate for further studies in the treatment of diabetic retinopathy.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139280868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Levicheva, A. Titkova, D. Bevzyuk, O. Berchenko
Alcoholism and chronic stress lead to impaired cognitive functions, which are regulated, in particular, by neurosteroid hormones. Exogenous administration of progesterone is one of the ways to influence the brain system of hormonal and neurotransmitter regulation. The effect of intranasal administration of low doses of progesterone on endogenous neurosteroid modulation of working and spatial memory in male rats with alcohol dependence and aggressive behavior was investigated. Alcohol dependence in male rats was modeled by voluntary intake of bread soaked in ethanol solution at a dose of 1.2 g/kg for 30 days. Aggressiveness was determined using the sensory contact method and the “partition” test. To study memory processes in rats, neuroethological methods of testing working (recognition of new objects) and spatial (orientation in the Barnes maze) memory were used. Progesterone was administered intranasally at a dose of 80 μg per rat for 10 days. Progesterone, testosterone, and cortisol levels were measured in the frontal neocortex (FC), hippocampus, and serum using enzyme-linked immunosorbent assay kits. The stimulatory effect of alcoholization on spatial memory and impairment of working memory in male rats with aggressive behavior was found. Zoosocial conflict on the background of prolonged alcohol consumption leads to impaired object recognition and spatial orientation against the background of neurosteroid imbalance: a decrease in progesterone and testosterone content in the FC, hippocampus, serum, and an increase in cortisol levels in these structures. Intranasal administration of progesterone to rats with alcohol dependence and aggressive behavior offsets the negative effects of confrontational relationships on working memory processes, restores the acquired experience to the baseline (however, the processes of object differentiation remain weakened); leads to improved spatial memory. The favorable effects of progesterone on memory are accompanied by a decrease in the imbalance of hormonal influences in brain structures with the restoration of progesterone and testosterone concentrations in the FC, hippocampus and serum against the background of weakening of stress-induced glucocorticoid activity. Therefore, intranasal administration of low doses of progesterone improves working and spatial memory in male rats with alcohol dependence and aggressive behavior due to the tendency to restore the balance of hormones (progesterone, testosterone, cortisol) in the brain structures responsible for memory.
{"title":"ENDOGENOUS AND EXOGENOUS NEUROSTEROIDAL MODULATION OF MEMORY IN RATS WITH ALCOHOL DEPENDENCE AND AGGRESSIVE BEHAVIOR","authors":"N. Levicheva, A. Titkova, D. Bevzyuk, O. Berchenko","doi":"10.15407/fz69.06.043","DOIUrl":"https://doi.org/10.15407/fz69.06.043","url":null,"abstract":"Alcoholism and chronic stress lead to impaired cognitive functions, which are regulated, in particular, by neurosteroid hormones. Exogenous administration of progesterone is one of the ways to influence the brain system of hormonal and neurotransmitter regulation. The effect of intranasal administration of low doses of progesterone on endogenous neurosteroid modulation of working and spatial memory in male rats with alcohol dependence and aggressive behavior was investigated. Alcohol dependence in male rats was modeled by voluntary intake of bread soaked in ethanol solution at a dose of 1.2 g/kg for 30 days. Aggressiveness was determined using the sensory contact method and the “partition” test. To study memory processes in rats, neuroethological methods of testing working (recognition of new objects) and spatial (orientation in the Barnes maze) memory were used. Progesterone was administered intranasally at a dose of 80 μg per rat for 10 days. Progesterone, testosterone, and cortisol levels were measured in the frontal neocortex (FC), hippocampus, and serum using enzyme-linked immunosorbent assay kits. The stimulatory effect of alcoholization on spatial memory and impairment of working memory in male rats with aggressive behavior was found. Zoosocial conflict on the background of prolonged alcohol consumption leads to impaired object recognition and spatial orientation against the background of neurosteroid imbalance: a decrease in progesterone and testosterone content in the FC, hippocampus, serum, and an increase in cortisol levels in these structures. Intranasal administration of progesterone to rats with alcohol dependence and aggressive behavior offsets the negative effects of confrontational relationships on working memory processes, restores the acquired experience to the baseline (however, the processes of object differentiation remain weakened); leads to improved spatial memory. The favorable effects of progesterone on memory are accompanied by a decrease in the imbalance of hormonal influences in brain structures with the restoration of progesterone and testosterone concentrations in the FC, hippocampus and serum against the background of weakening of stress-induced glucocorticoid activity. Therefore, intranasal administration of low doses of progesterone improves working and spatial memory in male rats with alcohol dependence and aggressive behavior due to the tendency to restore the balance of hormones (progesterone, testosterone, cortisol) in the brain structures responsible for memory.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"37 6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139281366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The review summarizes current literature data on the importance of vitamin D in bone cell function. An analytical search was conducted in the PubMed, MEDLINE, Embase, Scopus, and Web of Science databases from January 1, 2018, to June 01, 2023. The vitamin D metabolite 1α,25(OH)2D3 plays an important role in the regulation of mineral homeostasis and bone metabolism. It has catabolic and anabolic actions on osteoblasts, osteocytes and mature osteoclasts. In this review, we describe the direct and indirect effects of 1α,25(OH)2D3 on the function of mesenchymal stromal cells (MSCs), osteoblasts, osteocytes, and osteoclasts. Among the targets of vitamin D action in bone cells are vitamin D receptor (VDR) and cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). In osteoblasts and MSCs with CYP27B1 knockout, cell proliferation and differentiation are impaired, and in osteoclasts, the resorption activity and lifespan of these cells are increased. The role of VDR in bone cells was demonstrated in normal and VDR-knockout animal models. The relationship between 1α,25(OH)2D3 – VDR signal transduction by bone cells and calcium balance was analyzed. In osteocytes, as well as in osteoblasts, 1α,25(OH)2D3 regulates the expression of RANKL (receptor activator of nuclear factor kappa-B ligand)), and additionally in osteocytes regulates the expression of FGF-23. The interaction of many other factors in bone cells has been shown to control the biological activity of 1α,25(OH)2D3. Thus, the effect of vitamin D on bone cells is in the phase of active research and requires an in-depth study of the features of its autocrine and paracrine effects. Identification of the molecular links of the mechanism of action of 1α,25(OH)2D3 on bone metabolism will provide a fundamental basis for approaches to the treatment of vitamin D deficiency diseases.
本综述总结了当前有关维生素 D 对骨细胞功能重要性的文献数据。从2018年1月1日至2023年6月1日，在PubMed、MEDLINE、Embase、Scopus和Web of Science数据库中进行了分析检索。维生素 D 代谢产物 1α,25（OH）2D3 在矿物质平衡和骨代谢调节中发挥着重要作用。它对成骨细胞、骨细胞和成熟的破骨细胞具有分解和合成代谢作用。在这篇综述中，我们描述了 1α，25（OH）2D3 对间充质基质细胞（MSCs）、成骨细胞、骨细胞和破骨细胞功能的直接和间接影响。维生素 D 在骨细胞中的作用靶点包括维生素 D 受体（VDR）和细胞色素 P450 家族 27 B 亚家族成员 1（CYP27B1）。在 CYP27B1 基因敲除的成骨细胞和间充质干细胞中，细胞增殖和分化受到影响，而在破骨细胞中，这些细胞的吸收活性和寿命则会增加。在正常和 VDR 基因敲除的动物模型中，VDR 在骨细胞中的作用得到了证实。研究还分析了骨细胞的 1α,25（OH）2D3-VDR 信号转导与钙平衡之间的关系。在骨细胞和成骨细胞中，1α,25(OH)2D3 可调节 RANKL（核因子卡巴-B 配体受体激活剂）的表达，此外，在骨细胞中还可调节 FGF-23 的表达。骨细胞中许多其他因素的相互作用已被证明可以控制 1α，25（OH）2D3 的生物活性。因此，维生素 D 对骨细胞的影响正处于积极研究阶段，需要深入研究其自分泌和旁分泌效应的特点。确定 1α，25（OH）2D3 对骨代谢作用机制的分子环节，将为治疗维生素 D 缺乏症的方法提供基本依据。
{"title":"THE ROLE OF VITAMIN D IN THE FUNCTIONING OF BONE CELLS","authors":"N. Dedukh, N. Grygorieva","doi":"10.15407/fz69.06.108","DOIUrl":"https://doi.org/10.15407/fz69.06.108","url":null,"abstract":"The review summarizes current literature data on the importance of vitamin D in bone cell function. An analytical search was conducted in the PubMed, MEDLINE, Embase, Scopus, and Web of Science databases from January 1, 2018, to June 01, 2023. The vitamin D metabolite 1α,25(OH)2D3 plays an important role in the regulation of mineral homeostasis and bone metabolism. It has catabolic and anabolic actions on osteoblasts, osteocytes and mature osteoclasts. In this review, we describe the direct and indirect effects of 1α,25(OH)2D3 on the function of mesenchymal stromal cells (MSCs), osteoblasts, osteocytes, and osteoclasts. Among the targets of vitamin D action in bone cells are vitamin D receptor (VDR) and cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). In osteoblasts and MSCs with CYP27B1 knockout, cell proliferation and differentiation are impaired, and in osteoclasts, the resorption activity and lifespan of these cells are increased. The role of VDR in bone cells was demonstrated in normal and VDR-knockout animal models. The relationship between 1α,25(OH)2D3 – VDR signal transduction by bone cells and calcium balance was analyzed. In osteocytes, as well as in osteoblasts, 1α,25(OH)2D3 regulates the expression of RANKL (receptor activator of nuclear factor kappa-B ligand)), and additionally in osteocytes regulates the expression of FGF-23. The interaction of many other factors in bone cells has been shown to control the biological activity of 1α,25(OH)2D3. Thus, the effect of vitamin D on bone cells is in the phase of active research and requires an in-depth study of the features of its autocrine and paracrine effects. Identification of the molecular links of the mechanism of action of 1α,25(OH)2D3 on bone metabolism will provide a fundamental basis for approaches to the treatment of vitamin D deficiency diseases.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"18 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139280383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The review provides a pathophysiological analysis of what is currently known about the impact of acute and chronic stress on the functional state of the male and female reproductive systems. The relevance of research on the negative effects of stress on the reproductive system has increased significantly in recent years due to the COVID-19 pandemic and even more so after Russia’s aggression against Ukraine. Stress disrupts gamete maturation, libido, sexual behavior, mating, fertilization, pregnancy and delivery. In the structure of the etiology of these disorders, psycho-social stress prevails. The characteristics of stress-induced disorders of the reproductive system have features depending on the lifestyle of future parents, as well as on the period of life, starting from the embryonic to the end of the reproductive age. The hypothalamicpituitary-adrenocortical and hypothalamic-pituitary-gonadal systems, as well as oxidative-nitrosative stress, play a leading role in the pathogenesis of stress-induced disorders of the reproductive system. Modern data on the pathogenesis of stress-induced reproductive disorders should be the basis of preventive and therapeutic strategies.
{"title":"Stress-induced disorders of reproductive functions","authors":"A.G. Reznikov","doi":"10.15407/fz69.06.097","DOIUrl":"https://doi.org/10.15407/fz69.06.097","url":null,"abstract":"The review provides a pathophysiological analysis of what is currently known about the impact of acute and chronic stress on the functional state of the male and female reproductive systems. The relevance of research on the negative effects of stress on the reproductive system has increased significantly in recent years due to the COVID-19 pandemic and even more so after Russia’s aggression against Ukraine. Stress disrupts gamete maturation, libido, sexual behavior, mating, fertilization, pregnancy and delivery. In the structure of the etiology of these disorders, psycho-social stress prevails. The characteristics of stress-induced disorders of the reproductive system have features depending on the lifestyle of future parents, as well as on the period of life, starting from the embryonic to the end of the reproductive age. The hypothalamicpituitary-adrenocortical and hypothalamic-pituitary-gonadal systems, as well as oxidative-nitrosative stress, play a leading role in the pathogenesis of stress-induced disorders of the reproductive system. Modern data on the pathogenesis of stress-induced reproductive disorders should be the basis of preventive and therapeutic strategies.","PeriodicalId":12307,"journal":{"name":"Fiziolohichnyĭ zhurnal","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139281201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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