The review considers the effects of extracellular ATP mediated by plasma membrane purinoreceptors in the cells of different tissues, in particular, myometrium. Recently published results suggest that cytosolic ATP may also play a role of signaling molecule, as indicated by the detection of the ATP receptor not only in the plasma membrane, but also in mitochondria. The authors have shown that ionized Ca2+ concentration in the rat myometrium mitochondria matrix is regulated by ATP at the absence of exogenous Ca2+. ATP concentration-dependent increase of [Ca2+]m was not affected in the presence of the mitochondrial Ca2+-uniporter blocker ruthenium red, the mitochondrial pore blocker cyclosporine A, or ATP synthase inhibitor oligomycin. It is assumed that cytosolic ATP could be a signaling molecule that regulates at least the Ca2+ ions exchange in mitochondria. Keywords: Ca2+ ions exchange, extracellular and cytosolic ATP, mitochondria, P2X7 receptors
这篇综述探讨了细胞外 ATP 在不同组织细胞（尤其是子宫肌层）中由质膜嘌呤受体介导的作用。最近发表的研究结果表明，细胞质 ATP 也可能起到信号分子的作用，这不仅体现在质膜上，还体现在线粒体中检测到 ATP 受体。作者发现，在没有外源 Ca2+ 的情况下，大鼠子宫肌层线粒体基质中的电离 Ca2+ 浓度受 ATP 调节。在线粒体 Ca2+-uniporter 阻断剂钌红、线粒体孔阻断剂环孢素 A 或 ATP 合成酶抑制剂寡霉素存在的情况下，[Ca2+]m 的增加不受 ATP 浓度的影响。推测细胞质 ATP 可能是一种信号分子，至少能调节线粒体中的 Ca2+ 离子交换。关键词Ca2+离子交换 细胞外和细胞质ATP 线粒体 P2X7受体
{"title":"ATP as a signaling molecule","authors":"L. G. Babich, S. G. Shlykov, S. O. Kosterin","doi":"10.15407/ubj96.03.005","DOIUrl":"https://doi.org/10.15407/ubj96.03.005","url":null,"abstract":"The review considers the effects of extracellular ATP mediated by plasma membrane purinoreceptors in the cells of different tissues, in particular, myometrium. Recently published results suggest that cytosolic ATP may also play a role of signaling molecule, as indicated by the detection of the ATP receptor not only in the plasma membrane, but also in mitochondria. The authors have shown that ionized Ca2+ concentration in the rat myometrium mitochondria matrix is regulated by ATP at the absence of exogenous Ca2+. ATP concentration-dependent increase of [Ca2+]m was not affected in the presence of the mitochondrial Ca2+-uniporter blocker ruthenium red, the mitochondrial pore blocker cyclosporine A, or ATP synthase inhibitor oligomycin. It is assumed that cytosolic ATP could be a signaling molecule that regulates at least the Ca2+ ions exchange in mitochondria. Keywords: Ca2+ ions exchange, extracellular and cytosolic ATP, mitochondria, P2X7 receptors","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"46 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141339996","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}
Metabolic dysregulation and obesity are associated with many metabolic alterations, including impairment of insulin sensitivity and dyslipidemia. Recent studies highlight the key role of phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchange proteins (PREX proteins) in the pathogenesis of obesity, advocating further elucidation of their potential therapeutic implications. The present study aimed to estimate the serum level of PREX proteins and its potential association with insulin resistance markers and plasma lipids level in obese and overweight non-diabetic patients. The study included 30 persons classified as obese, 30 as overweight, and 30 healthy individuals of similar age and gender. The levels of PREX1 and PREX2 were measured using ELISA kits, insulin, fasting glucose, glycosylated hemoglobin and total lipid profile were determined using appropriate photometric kits. HOMA-IR was used as a measure of insulin sensitivity. According to the obtained results, obese non-diabetic patients had higher serum PREX1 level compared to both overweight and normal-weight individuals. PREX1 correlated positively with the markers of insulin resistance and dyslipidemia. PREX2 level was shown to be lower both in obese compared to overweight patients and in overweight compared to normal-weight individuals. PREX2 correlated negatively with the markers of insulin resistance but not with the markers of dyslipidemia. Keywords: dyslipidemia, insulin resistance, obesity, overweight, PREX proteins
{"title":"PREX proteins level correlation with insulin resistance markers and lipid profile in obese and overweight non-diabetic patients","authors":"N. Hamza, A. A. Kasim, W. E. Hameed","doi":"10.15407/ubj96.03.039","DOIUrl":"https://doi.org/10.15407/ubj96.03.039","url":null,"abstract":"Metabolic dysregulation and obesity are associated with many metabolic alterations, including impairment of insulin sensitivity and dyslipidemia. Recent studies highlight the key role of phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchange proteins (PREX proteins) in the pathogenesis of obesity, advocating further elucidation of their potential therapeutic implications. The present study aimed to estimate the serum level of PREX proteins and its potential association with insulin resistance markers and plasma lipids level in obese and overweight non-diabetic patients. The study included 30 persons classified as obese, 30 as overweight, and 30 healthy individuals of similar age and gender. The levels of PREX1 and PREX2 were measured using ELISA kits, insulin, fasting glucose, glycosylated hemoglobin and total lipid profile were determined using appropriate photometric kits. HOMA-IR was used as a measure of insulin sensitivity. According to the obtained results, obese non-diabetic patients had higher serum PREX1 level compared to both overweight and normal-weight individuals. PREX1 correlated positively with the markers of insulin resistance and dyslipidemia. PREX2 level was shown to be lower both in obese compared to overweight patients and in overweight compared to normal-weight individuals. PREX2 correlated negatively with the markers of insulin resistance but not with the markers of dyslipidemia. Keywords: dyslipidemia, insulin resistance, obesity, overweight, PREX proteins","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"18 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141340946","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}
V. Orysyk, L. Garmanchuk, S. Orysyk, Yu. L. Zborovskii, S. Shishkina, I. Stupak, P. Novikova, D. Ostapchenko, N. Khranovska, V. Pekhnyo, M. Vovk
The search for new effective drugs in the treatment of neoplasm remains relevant even today, since the adaptation of transformed cells to the action of classical drugs contributes to the emergence of drug resistance. This applies to a number of classic chemotherapy drugs of the platinum series, in particular cisplatin. In this work, we describe the effect of novel analogs of cisplatin on HepG2 cells and on the key enzyme of antioxidant protection system gammaglutamyltranspeptidase, which plays an important role in the acquisition of drug resistance to anticancer drugs by tumor cells. New mononuclear iodide n,π-chelate complexes of Pt(II) with substituted thioureas N-allylmorpholine-4-carbothioamide or 3-allyl-1,1-diethylthiourea were obtained as analogs of cisplatin. All compounds were investigated by UV-Vis, IR, and 1H/13С NMR spectra. Complex I was described by single-crystal X-ray diffraction study. Also, the effect of these analogs on alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, which are marker enzymes of liver cells, release of which into the blood indicates liver pathologies, was investigated. All studies were carried out in comparison with chloride n,π-chelate complexes of platinum obtained earlier (however, the effect of these chloride analogs of platinum on enzymes of the hepatobiliary system was investigated for the first time in this work). The results have shown that the studied compounds are better cytostatics/cytotoxics than cisplatin both according to IC50 and apoptosis level of HepG2 cells. It is established that, for the most part, effect of the studied complexes is reduced to a decrease in the degree of malignancy of cells of hepatocyte lines and the activity of LDH and GHT, as well as a decrease in consumed glucose. Keywords: alanine aminotransferase, aspartate aminotransferase, gammaglutamyltranspeptidase, lactate dehydrogenase, NMR spectroscopy, n‚π-chelates, thioureas
{"title":"Iodide n,π-chelate complexes of platinum(II) based on N-allyl substituted thioureas and their effect on the activity of hepatobiliary system enzymes in comparison with chloride analogs","authors":"V. Orysyk, L. Garmanchuk, S. Orysyk, Yu. L. Zborovskii, S. Shishkina, I. Stupak, P. Novikova, D. Ostapchenko, N. Khranovska, V. Pekhnyo, M. Vovk","doi":"10.15407/ubj96.03.075","DOIUrl":"https://doi.org/10.15407/ubj96.03.075","url":null,"abstract":"The search for new effective drugs in the treatment of neoplasm remains relevant even today, since the adaptation of transformed cells to the action of classical drugs contributes to the emergence of drug resistance. This applies to a number of classic chemotherapy drugs of the platinum series, in particular cisplatin. In this work, we describe the effect of novel analogs of cisplatin on HepG2 cells and on the key enzyme of antioxidant protection system gammaglutamyltranspeptidase, which plays an important role in the acquisition of drug resistance to anticancer drugs by tumor cells. New mononuclear iodide n,π-chelate complexes of Pt(II) with substituted thioureas N-allylmorpholine-4-carbothioamide or 3-allyl-1,1-diethylthiourea were obtained as analogs of cisplatin. All compounds were investigated by UV-Vis, IR, and 1H/13С NMR spectra. Complex I was described by single-crystal X-ray diffraction study. Also, the effect of these analogs on alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, which are marker enzymes of liver cells, release of which into the blood indicates liver pathologies, was investigated. All studies were carried out in comparison with chloride n,π-chelate complexes of platinum obtained earlier (however, the effect of these chloride analogs of platinum on enzymes of the hepatobiliary system was investigated for the first time in this work). The results have shown that the studied compounds are better cytostatics/cytotoxics than cisplatin both according to IC50 and apoptosis level of HepG2 cells. It is established that, for the most part, effect of the studied complexes is reduced to a decrease in the degree of malignancy of cells of hepatocyte lines and the activity of LDH and GHT, as well as a decrease in consumed glucose. Keywords: alanine aminotransferase, aspartate aminotransferase, gammaglutamyltranspeptidase, lactate dehydrogenase, NMR spectroscopy, n‚π-chelates, thioureas","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"74 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141338203","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}
Z. M. A. A. Hamodat, H. H. Abdulwahhab, A. R. M. T. Hamodat
Search for reliable biomarkers for predicting progression of breast cancer is essential in managing the disease. So, we are trying to provide new insights into the potential role of alpha-fucosidase (AFU) as a putative prognostic biomarker in breast cancer as compared to classic markers. The study included 56 women with breast cancer; 25 had early breast cancer, and the rest (31) had metastatic breast cancer. Thirty healthy women were considered a control group. Early breast cancer patients had a significantly increased (P ≤ 0.0001) AFU level compared with the control group. A non-significant difference in the De-ritis ratio appeared for early breast cancer compared with control. Metastatic breast cancer had a significantly (P ≤ 0.0001) increased AFU and De-ritis ratio compared with early breast cancer and the control group. A positive significant (P = 0.01) correlation exists between AFU level, age factor (r = 0.295), and the De-ritis ratio in breast cancer patients. We can conclude that it is possible to consider alpha-L-fucosidase (AFU) as a putative prognostic biomarker in breast cancer more potent than the ratio of De-Ritis. Moreover, the coincidence of elevated AFU and De-ritis levels in metastatic breast cancer gives us an idea of the stage of the disease. Keywords: alpha-L-fucosidase, early breast cancer, metastasis, the De-ritis ratio
{"title":"Alpha-L-fucosidase as a putative prognostic biomarker in breast cancer","authors":"Z. M. A. A. Hamodat, H. H. Abdulwahhab, A. R. M. T. Hamodat","doi":"10.15407/ubj96.03.057","DOIUrl":"https://doi.org/10.15407/ubj96.03.057","url":null,"abstract":"Search for reliable biomarkers for predicting progression of breast cancer is essential in managing the disease. So, we are trying to provide new insights into the potential role of alpha-fucosidase (AFU) as a putative prognostic biomarker in breast cancer as compared to classic markers. The study included 56 women with breast cancer; 25 had early breast cancer, and the rest (31) had metastatic breast cancer. Thirty healthy women were considered a control group. Early breast cancer patients had a significantly increased (P ≤ 0.0001) AFU level compared with the control group. A non-significant difference in the De-ritis ratio appeared for early breast cancer compared with control. Metastatic breast cancer had a significantly (P ≤ 0.0001) increased AFU and De-ritis ratio compared with early breast cancer and the control group. A positive significant (P = 0.01) correlation exists between AFU level, age factor (r = 0.295), and the De-ritis ratio in breast cancer patients. We can conclude that it is possible to consider alpha-L-fucosidase (AFU) as a putative prognostic biomarker in breast cancer more potent than the ratio of De-Ritis. Moreover, the coincidence of elevated AFU and De-ritis levels in metastatic breast cancer gives us an idea of the stage of the disease. Keywords: alpha-L-fucosidase, early breast cancer, metastasis, the De-ritis ratio","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"1 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141341854","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}
In the 21st century, it is time to recognize the essential role of women in science. The study carried out by women-scientists makes it possible to combine brightness of mind, deep knowledge with humaneness and wisdom. Their approaches to the problems and the ways to solve them are largely determined by their maps of meaning and existential experience that can enrich and expand the scientific field and, as a result, can offer unexpected but most effective ways to solve the problem. However, women face obstacles in advancing their careers in science, and the situation is even more discouraging when it comes to winning science awards, the most prestigious of which is the Nobel Prize. Between 1901 and 2023, the Nobel Prizes were awarded 621 times to 965 individuals and 27 organizations, but only 64 of them were women-scientists. While we recognize and praise all women – Nobel laureates, this paper pays special attention to women who have received Nobel Prizes in Chemistry and Physiology or Medicine and briefly outlines their scientific achievements. A more detailed description of their life and scientific journey will be provided in subsequent articles. Keywords: the Nobel Prize in Chemistry and in Physiology or Medicine, women – Nobel Prize winners, women-scientists
{"title":"It is time to pay tribute to women in science: the women who won the Nobel prizes in Chemistry and Physiology or Medicine","authors":"T. Danylova, S. Komisarenko","doi":"10.15407/ubj96.03.122","DOIUrl":"https://doi.org/10.15407/ubj96.03.122","url":null,"abstract":"In the 21st century, it is time to recognize the essential role of women in science. The study carried out by women-scientists makes it possible to combine brightness of mind, deep knowledge with humaneness and wisdom. Their approaches to the problems and the ways to solve them are largely determined by their maps of meaning and existential experience that can enrich and expand the scientific field and, as a result, can offer unexpected but most effective ways to solve the problem. However, women face obstacles in advancing their careers in science, and the situation is even more discouraging when it comes to winning science awards, the most prestigious of which is the Nobel Prize. Between 1901 and 2023, the Nobel Prizes were awarded 621 times to 965 individuals and 27 organizations, but only 64 of them were women-scientists. While we recognize and praise all women – Nobel laureates, this paper pays special attention to women who have received Nobel Prizes in Chemistry and Physiology or Medicine and briefly outlines their scientific achievements. A more detailed description of their life and scientific journey will be provided in subsequent articles. Keywords: the Nobel Prize in Chemistry and in Physiology or Medicine, women – Nobel Prize winners, women-scientists","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141341340","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 article examines the impact of cooperation between The Ukrainian Biochemical Journal (UBJ) and the international association RECOOP HST on the journal’s development in 2019-2023. During this period, 324 articles were published in the journal. Most of them are written by Ukrainian authors (79.9%). Foreign authors (20.1%) are representatives of 15 countries. An online manuscript handling and reviewing system were implemented on the journal’s website, which increased the number of articles received by the editorial office and allowed for a more careful selection of manuscripts at the initial evaluation stage. As a result, the percentage of rejected manuscripts increased from 36.5 to 67.7%. RECOOP’s support has also played a key role in improving the quality of UBJ’s publications through the renewal of its editorial board and expanding its international reviewer base. In collaboration with RECOOP, eight special issues of UBJ were produced separately, including four themed issues. In total, 56 articles (110 citations) were published in these issues. The number of visitors to UBJ’s website almost tripled during the mentioned period. Currently, UBJ’s Scimago Scientific Journal Rank (SJR) for 2022/2023 is 0.169, the h-index is 20, and the Impact Score is 0.63. A conclusion is made that the cooperation with RECOOP contributed to the publication of better scientific articles, the involvement of highly qualified experts in the peer review process, and stricter adherence by the journal to the fundamental provisions and ethical standards, thereby leading to an elevation in UBJ’s rating and recognition in the global scientific arena. Keywords: COMET, increasing UBJ’s global visibility, project implementation, RECOOP, thematic issue, UBJ
{"title":"Progress of The Ukrainian Biochemical Journal thanks to Collaboration with RECOOP HST Association","authors":"M. Grigorieva, V. Chernyshenko, S. Vari","doi":"10.15407/ubj96.03.143","DOIUrl":"https://doi.org/10.15407/ubj96.03.143","url":null,"abstract":"The article examines the impact of cooperation between The Ukrainian Biochemical Journal (UBJ) and the international association RECOOP HST on the journal’s development in 2019-2023. During this period, 324 articles were published in the journal. Most of them are written by Ukrainian authors (79.9%). Foreign authors (20.1%) are representatives of 15 countries. An online manuscript handling and reviewing system were implemented on the journal’s website, which increased the number of articles received by the editorial office and allowed for a more careful selection of manuscripts at the initial evaluation stage. As a result, the percentage of rejected manuscripts increased from 36.5 to 67.7%. RECOOP’s support has also played a key role in improving the quality of UBJ’s publications through the renewal of its editorial board and expanding its international reviewer base. In collaboration with RECOOP, eight special issues of UBJ were produced separately, including four themed issues. In total, 56 articles (110 citations) were published in these issues. The number of visitors to UBJ’s website almost tripled during the mentioned period. Currently, UBJ’s Scimago Scientific Journal Rank (SJR) for 2022/2023 is 0.169, the h-index is 20, and the Impact Score is 0.63. A conclusion is made that the cooperation with RECOOP contributed to the publication of better scientific articles, the involvement of highly qualified experts in the peer review process, and stricter adherence by the journal to the fundamental provisions and ethical standards, thereby leading to an elevation in UBJ’s rating and recognition in the global scientific arena. Keywords: COMET, increasing UBJ’s global visibility, project implementation, RECOOP, thematic issue, UBJ","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"22 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141343018","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}
S. O. Kosterin, Т. О. Veklich, O. І. Kalchenko, A. I. Vovk, R. Rodik, О. А. Shkrabak
The kinetic model of calix[4]arene-induced ATP hydrolysis was elaborated. It is assumed that calix[4]arene С-107 molecules form a complex with nucleoside triphosphate, ensuring the release of inorganic phosphate Рі, and then switch into an inactive state. Inactive calix[4]arene molecules are no longer able to form a complex with ATP and, accordingly, to provide hydrolysis of nucleoside triphosphate. In the author’s experimental studies, it was possible to explain the kinetic properties of the reaction, namely: the insignificant output of the reaction end product Pi; the quantitative regularities of the plateau (time-wise) accumulation of the reaction product when the concentration of calix[4]arene C-107 or ATP changes; the reciprocal dependence of the ATP half conversion on its concentration; the correspondence of the initial reaction rate dependence on the calix[4]arene and ATP concentration to the Michaelis-Menten equation. The final decision regarding the molecular mechanism of calix[4]arene-induced ATP hydrolysis requires further experimental and theoretical studies. Keywords: calixarenes, empirical kinetic analysis, hydrolysis of ATP
详细阐述了钙[4]炔诱导 ATP 水解的动力学模型。假设钙[4]炔С-107 分子与三磷酸核苷形成复合物，确保无机磷酸Рі的释放，然后转入非活性状态。无活性的钙[4]炔分子不再能与 ATP 形成复合物，因此也就无法水解三磷酸核苷。在作者的实验研究中，有可能解释该反应的动力学特性，即：反应终产物 Pi 的输出微不足道；当钙[4]炔 C-107 或 ATP 的浓度发生变化时，反应产物的高原（时间上）积累具有定量规律性；ATP 的半转化率与其浓度互为依赖关系；初始反应速率与钙[4]炔和 ATP 浓度的依赖关系与 Michaelis-Menten 方程相对应。钙[4]烯诱导 ATP 水解的分子机理还需要进一步的实验和理论研究才能最终确定。关键词：钙[4]烯；经验动力学分析；ATP水解
{"title":"Kinetic regularities and a possible mechanism of ATP non-enzymatic hydrolysis induced by calix[4]arene С-107","authors":"S. O. Kosterin, Т. О. Veklich, O. І. Kalchenko, A. I. Vovk, R. Rodik, О. А. Shkrabak","doi":"10.15407/ubj96.03.108","DOIUrl":"https://doi.org/10.15407/ubj96.03.108","url":null,"abstract":"The kinetic model of calix[4]arene-induced ATP hydrolysis was elaborated. It is assumed that calix[4]arene С-107 molecules form a complex with nucleoside triphosphate, ensuring the release of inorganic phosphate Рі, and then switch into an inactive state. Inactive calix[4]arene molecules are no longer able to form a complex with ATP and, accordingly, to provide hydrolysis of nucleoside triphosphate. In the author’s experimental studies, it was possible to explain the kinetic properties of the reaction, namely: the insignificant output of the reaction end product Pi; the quantitative regularities of the plateau (time-wise) accumulation of the reaction product when the concentration of calix[4]arene C-107 or ATP changes; the reciprocal dependence of the ATP half conversion on its concentration; the correspondence of the initial reaction rate dependence on the calix[4]arene and ATP concentration to the Michaelis-Menten equation. The final decision regarding the molecular mechanism of calix[4]arene-induced ATP hydrolysis requires further experimental and theoretical studies. Keywords: calixarenes, empirical kinetic analysis, hydrolysis of ATP","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"73 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141338034","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}
A. Mykytenko, O. Akimov, G. Yeroshenko, K. Neporada
Modulation of the AMP-activated protein kinase (AMPK) pathway activity is considered to be a promising option in the development of approaches to chronic alcoholic hepatitis treatment. Phenformin, which is a biguanide, has been reported to increase AMPK activity. The aim of this work was to estimate the effect of phenformin as AMPK activator on the development of oxidative-nitrosative stress in the liver of rats under conditions of long-term ethanol administration. The experiments were performed on 24 male Wistar rats, divided into 4 groups: control; animals, which received phenformin hydrochloride orally at a dose of 10 mg/kg daily for 63 days; animals with a forced intermittent alcoholization for 5 days by intraperitoneal administration of 16.5% ethanol solution in 5% glucose at the rate of 4 ml/kg b.w. and subsequent transfer to 10% ethanol as the only source of drinking; animals with chronic alcohol hepatitis simulation and phenformin administration. Superoxide dismutase, catalase, NO synthase isoforms activity, superoxide anion radical production, concentration of malonic dialdehyde, peroxynitrite, nitrites, nitrosothiols concentration and oxidative modification of proteins (OMP) were estimated in liver homogenates. The increased production of oxygen and nitrogen active forms and OMP intensification in the liver of rats under long-term administration of ethanol was detected. Phenformin introduction under long-term ethanol administration was shown to limit the excess peroxynitrite formation and to prevent oxidative damage to rat liver proteins. Keywords: AMP-activated protein kinase., chronic alcoholic hepatitis, liver, oxidative and nitrosative stress, phenformin
{"title":"Phenformin attenuates the oxidative-nitrosative stress in the liver of rats under long-term ethanol administration","authors":"A. Mykytenko, O. Akimov, G. Yeroshenko, K. Neporada","doi":"10.15407/ubj96.03.022","DOIUrl":"https://doi.org/10.15407/ubj96.03.022","url":null,"abstract":"Modulation of the AMP-activated protein kinase (AMPK) pathway activity is considered to be a promising option in the development of approaches to chronic alcoholic hepatitis treatment. Phenformin, which is a biguanide, has been reported to increase AMPK activity. The aim of this work was to estimate the effect of phenformin as AMPK activator on the development of oxidative-nitrosative stress in the liver of rats under conditions of long-term ethanol administration. The experiments were performed on 24 male Wistar rats, divided into 4 groups: control; animals, which received phenformin hydrochloride orally at a dose of 10 mg/kg daily for 63 days; animals with a forced intermittent alcoholization for 5 days by intraperitoneal administration of 16.5% ethanol solution in 5% glucose at the rate of 4 ml/kg b.w. and subsequent transfer to 10% ethanol as the only source of drinking; animals with chronic alcohol hepatitis simulation and phenformin administration. Superoxide dismutase, catalase, NO synthase isoforms activity, superoxide anion radical production, concentration of malonic dialdehyde, peroxynitrite, nitrites, nitrosothiols concentration and oxidative modification of proteins (OMP) were estimated in liver homogenates. The increased production of oxygen and nitrogen active forms and OMP intensification in the liver of rats under long-term administration of ethanol was detected. Phenformin introduction under long-term ethanol administration was shown to limit the excess peroxynitrite formation and to prevent oxidative damage to rat liver proteins. Keywords: AMP-activated protein kinase., chronic alcoholic hepatitis, liver, oxidative and nitrosative stress, phenformin","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"58 51","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141338883","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}
Isoniazid and rifampicin are reliable drugs against tuberculosis, but while effective, their use is associated with the risk of drug-induced liver damage. Embelin, a natural parabenzoquinone derived from the Embelia ribes plant, has gained attention for its potential therapeutic properties, antioxidant and organ-protective effects. The study aimed to assess the hepatoprotective properties of embelin against liver damage induced by isoniazid and rifampicin in rats. Wistar rats were used, and liver damage was induced by administration of isoniazid (100 mg/kg) and rifampicin (100 mg/kg). Embelin was given at doses of 50, 75, and 100 mg/kg for 21 days. All the drugs were given orally. Serum levels of the oxidative stress markers, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) activity measured by enzymatic assay kits (Elabscience, China), and the levels of tumour necrosis factor-α (TNF-α), interleukins IL-1β and IL-6 measured by ELISA kits (Randox, UK) were estimated. Embelin administration at varying doses effectively restored AST, ALT, ALP, SOD and catalase activity and notably decreased MDA and nitric oxide concentration as well as expression of inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum of animals with drug-induced liver damage. These findings underscore embelin’s hepatoprotective effects, likely attributed to its radical scavenging properties and ability to suppress cytokine production. Keywords: antioxidant effect, cytokine suppression, embelin, hepatoprotection, isoniazid, rifampicin
{"title":"Embelin mitigates hepatotoxicity induced by isoniazid and rifampicin in rats","authors":"O. F. Mosa","doi":"10.15407/ubj96.03.048","DOIUrl":"https://doi.org/10.15407/ubj96.03.048","url":null,"abstract":"Isoniazid and rifampicin are reliable drugs against tuberculosis, but while effective, their use is associated with the risk of drug-induced liver damage. Embelin, a natural parabenzoquinone derived from the Embelia ribes plant, has gained attention for its potential therapeutic properties, antioxidant and organ-protective effects. The study aimed to assess the hepatoprotective properties of embelin against liver damage induced by isoniazid and rifampicin in rats. Wistar rats were used, and liver damage was induced by administration of isoniazid (100 mg/kg) and rifampicin (100 mg/kg). Embelin was given at doses of 50, 75, and 100 mg/kg for 21 days. All the drugs were given orally. Serum levels of the oxidative stress markers, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) activity measured by enzymatic assay kits (Elabscience, China), and the levels of tumour necrosis factor-α (TNF-α), interleukins IL-1β and IL-6 measured by ELISA kits (Randox, UK) were estimated. Embelin administration at varying doses effectively restored AST, ALT, ALP, SOD and catalase activity and notably decreased MDA and nitric oxide concentration as well as expression of inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum of animals with drug-induced liver damage. These findings underscore embelin’s hepatoprotective effects, likely attributed to its radical scavenging properties and ability to suppress cytokine production. Keywords: antioxidant effect, cytokine suppression, embelin, hepatoprotection, isoniazid, rifampicin","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"21 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141342034","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}
Mai M. Sharabi, Amr A. Zahra, Azza M. Elamir, Talal A. Abd El Raheem, Nesreen M. Aboraia
Vitiligo belongs to chronic autoimmune diseases and results in a loss of functioning melanocytes and skin depigmentation. Nuclear enriched abundant transcript 1 (NEAT-1) is a long non-coding RNA that has a vital role in the diagnostics and treatment of certain autoimmune and inflammatory diseases. It is suggested that NEAT-1 can increase the pro-inflammatory cytokine level via regulatory network. The aim of the work was to measure the serum level of NEAT-1 and IL-6 in vitiligo patients compared with healthy controls and to estimate its relation to disease activity. In the study, 60 individuals were enrolled subdivided into 40 vitiligo patients and 20 healthy controls of similar age and gender. NEAT-1 expression was detected by Quantitative real-time PCR, and IL-6 level was measured by ELISA. To assess the severity of the disease Vitiligo area scoring index (VASI) was calculated. Results showed that there was a significant increase in both NEAT-1 and IL-6 levels in vitiligo patients compared with the control group. A positive correlation between NEAT-1 and IL-6 levels and a negative correlation between NEAT-1 level and VASI score was revealed. The elevated serum levels of NEAT-1 and IL-6 suggest that these circulating biomarkers have promise as diagnostic indicators for vitiligo and possible targets for therapeutic interventions. Keywords: IL-6, NEAT-1, non-coding RNA, serum, vitiligo
{"title":"Non-coding RNA NEAT-1 and interleukin-6 as diagnostic indicators for vitiligo","authors":"Mai M. Sharabi, Amr A. Zahra, Azza M. Elamir, Talal A. Abd El Raheem, Nesreen M. Aboraia","doi":"10.15407/ubj96.03.066","DOIUrl":"https://doi.org/10.15407/ubj96.03.066","url":null,"abstract":"Vitiligo belongs to chronic autoimmune diseases and results in a loss of functioning melanocytes and skin depigmentation. Nuclear enriched abundant transcript 1 (NEAT-1) is a long non-coding RNA that has a vital role in the diagnostics and treatment of certain autoimmune and inflammatory diseases. It is suggested that NEAT-1 can increase the pro-inflammatory cytokine level via regulatory network. The aim of the work was to measure the serum level of NEAT-1 and IL-6 in vitiligo patients compared with healthy controls and to estimate its relation to disease activity. In the study, 60 individuals were enrolled subdivided into 40 vitiligo patients and 20 healthy controls of similar age and gender. NEAT-1 expression was detected by Quantitative real-time PCR, and IL-6 level was measured by ELISA. To assess the severity of the disease Vitiligo area scoring index (VASI) was calculated. Results showed that there was a significant increase in both NEAT-1 and IL-6 levels in vitiligo patients compared with the control group. A positive correlation between NEAT-1 and IL-6 levels and a negative correlation between NEAT-1 level and VASI score was revealed. The elevated serum levels of NEAT-1 and IL-6 suggest that these circulating biomarkers have promise as diagnostic indicators for vitiligo and possible targets for therapeutic interventions. Keywords: IL-6, NEAT-1, non-coding RNA, serum, vitiligo","PeriodicalId":508485,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"21 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141341319","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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