O. Hrabovska, K. L. Shamelashvili, O. Shtemenko, N. Shtemenko
Contemporary investigations of mechanisms of resistance to platinides showed the key role of copper metabolism in cancer patients and proposed possible methods to attenuate the resistance by modulation of copper transporting mechanisms. In this vein, investigation of ceruloplasmin (Cp) levels – the main coppercontaining protein in blood, in experiments with tumor-containing animals upon cytostatics administration is topical and has great importance. the concentration of Cp was measured in the serum of tumor-bearing rats with ordinary (t8) and resistant to cisplatin (t8*) Guerin’s carcinoma upon administration of cisplatin and quadruple bonding dirhenium(III) compound dichlorotetra-μ-isobutyratodirhenium(ІІІ) (I) in different medicamental forms. It was shown that development of tumor in t8 group led to increasing of concentration of Cp in 3.7 times and in T8* group – more than in 8 times in comparison to control, confirming the essential role of Cp in the formation of resistance phenomenon. administration of cisplatin together with I led to effective inhibition of tumor in groups with t8 and t8*, indicating decreased resistance in the group t8*. Greater reduction of Cp levels was observed in the groups with t8* upon administration of the rhenium-plati num antitumor system, than in groups with t8, that underlines the importance of further investigations of the dirhenium(III) compounds in the resistance to cytostatics cancer models. Some mechanisms concerning the regulation of copper homeostasis and properties of nano-composites are discussed.
{"title":"The concentration of ceruloplasmin in blood of tumor-bearing rats after administration of a dirhenium(III) compound and cisplatin","authors":"O. Hrabovska, K. L. Shamelashvili, O. Shtemenko, N. Shtemenko","doi":"10.15407/ubj91.06.079","DOIUrl":"https://doi.org/10.15407/ubj91.06.079","url":null,"abstract":"Contemporary investigations of mechanisms of resistance to platinides showed the key role of copper metabolism in cancer patients and proposed possible methods to attenuate the resistance by modulation of copper transporting mechanisms. In this vein, investigation of ceruloplasmin (Cp) levels – the main coppercontaining protein in blood, in experiments with tumor-containing animals upon cytostatics administration is topical and has great importance. the concentration of Cp was measured in the serum of tumor-bearing rats with ordinary (t8) and resistant to cisplatin (t8*) Guerin’s carcinoma upon administration of cisplatin and quadruple bonding dirhenium(III) compound dichlorotetra-μ-isobutyratodirhenium(ІІІ) (I) in different medicamental forms. It was shown that development of tumor in t8 group led to increasing of concentration of Cp in 3.7 times and in T8* group – more than in 8 times in comparison to control, confirming the essential role of Cp in the formation of resistance phenomenon. administration of cisplatin together with I led to effective inhibition of tumor in groups with t8 and t8*, indicating decreased resistance in the group t8*. Greater reduction of Cp levels was observed in the groups with t8* upon administration of the rhenium-plati num antitumor system, than in groups with t8, that underlines the importance of further investigations of the dirhenium(III) compounds in the resistance to cytostatics cancer models. Some mechanisms concerning the regulation of copper homeostasis and properties of nano-composites are discussed.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"91 1","pages":"79-85"},"PeriodicalIF":0.0,"publicationDate":"2019-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45571384","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}
Yu. E. Kolupaev, A. I. Kokorev, T. Yastreb, E. I. Horielova
Polyamines are multifunctional stress metabolites of plants. However, information on the effect of exo genous polyamines on plant resistance to high temperatures is contradictory, and it remains unclear which signal mediators are involved in the realization of their physiological effects. The possible involvement of hydrogen peroxide as a mediator under the action of exogenous diamine putrescine on the resistance of etiolated wheat seedlings (Triticum aestivum l.) to hyperthermia (10-minute heating at 46 °C) and the functioning of antioxidant system was investigated. It was established that the treatment of seedlings with putrescine in 0.25–2.5 mM concentrations caused a significant increase in their heat resistance. In response to the putrescine effect, a transient increase in the H2o2 content occurred in the root cells. This effect was eliminated by treatment of seedlings with a diamine oxidase inhibitor aminoguanidine and an NADPH oxidase inhibitor imidazole. These inhibitors, as well as the scavenger of hydrogen peroxide dimethylthiourea (DMTU), mitigated the effects of increased heat resistance of seedlings and increased activity of superoxide dismutase and catalase caused by putrescine. Under the influence of DMTU and imidazole, but not aminoguanidine, the effect of increasing the activity of guaiacol peroxidase in the roots of seedlings treated with putrescine was eliminated. The conclusion was made about the role of hydrogen peroxide and the possible participation of diamine oxidase and NADPH oxidase in its formation during the implementation of the stressprotective effect of putrescine on wheat seedlings.
{"title":"Hydrogen peroxide as a signal mediator at inducing heat resistance in wheat seedlings by putrescine","authors":"Yu. E. Kolupaev, A. I. Kokorev, T. Yastreb, E. I. Horielova","doi":"10.15407/ubj91.06.103","DOIUrl":"https://doi.org/10.15407/ubj91.06.103","url":null,"abstract":"Polyamines are multifunctional stress metabolites of plants. However, information on the effect of exo genous polyamines on plant resistance to high temperatures is contradictory, and it remains unclear which signal mediators are involved in the realization of their physiological effects. The possible involvement of hydrogen peroxide as a mediator under the action of exogenous diamine putrescine on the resistance of etiolated wheat seedlings (Triticum aestivum l.) to hyperthermia (10-minute heating at 46 °C) and the functioning of antioxidant system was investigated. It was established that the treatment of seedlings with putrescine in 0.25–2.5 mM concentrations caused a significant increase in their heat resistance. In response to the putrescine effect, a transient increase in the H2o2 content occurred in the root cells. This effect was eliminated by treatment of seedlings with a diamine oxidase inhibitor aminoguanidine and an NADPH oxidase inhibitor imidazole. These inhibitors, as well as the scavenger of hydrogen peroxide dimethylthiourea (DMTU), mitigated the effects of increased heat resistance of seedlings and increased activity of superoxide dismutase and catalase caused by putrescine. Under the influence of DMTU and imidazole, but not aminoguanidine, the effect of increasing the activity of guaiacol peroxidase in the roots of seedlings treated with putrescine was eliminated. The conclusion was made about the role of hydrogen peroxide and the possible participation of diamine oxidase and NADPH oxidase in its formation during the implementation of the stressprotective effect of putrescine on wheat seedlings.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"91 1","pages":"103-111"},"PeriodicalIF":0.0,"publicationDate":"2019-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41363462","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}
Although hypertriglyceridemia (HTG) frequently occurs in hypertensive patients and may increase cardiovascular risk, the need and way of its reduction remain controversial. The objectives of the research was to compare lipid profiles, parameters of glucose homeostasis, comorbidity, a 5-year survival without cardiovascular events in very high risk hypertensive (VHRH) patients with and without HTG, who received moderate intensity atorvastatin therapy. After initial assessment 107 VHRH subjects were divided into two groups, i.e., without (n=49) and with HTG (n=58). During observation once annually patients were interviewing about prior hospitalizations with further screening for diabetes. Combined endpoint included hospitalization due acute myocardial infarction, decompensated heart failure, stroke or death. Survival was analyzed by Kaplan-Meier’s method. Nonparametric methods were used for statistical analysis. Higher median values of logarithmic value of triglycerides-to-HDL-cholesterol ratio, lipid accumulation product, fasting insulin, and HOMA index were observed in group 2 ( P< 0.002) that reflect predominance of small dense LDL particles, ectopic lipid deposition and insulin resistance. Patients with HTG more commonly had type 2 diabetes (58.6% vs 34.5%, including first-detected cases during initial assessments and observation, P=0.02), liver steatosis (81.0% vs 55.1%, P=0.006), and lithogenic gallbladder disorders (55.2% vs 34.7%, P=0.05). Women with HTG frequently had a history of hysterovariectomy (55.2% vs 19.0%, Р =0.018). Despite long-term statin therapy, they often failed to reach recommended LDL-C targets and had worse survival due to significantly higher incidence of composite endpoint (39.6% vs 22.4%, P=0.027). Further researches are necessary to find safe and effective strategy for secondary prevention in this population.
虽然高甘油三酯血症(HTG)在高血压患者中经常发生，并可能增加心血管风险，但其降低的必要性和方法仍存在争议。该研究的目的是比较接受中等强度阿托伐他汀治疗的高危高血压(VHRH)合并和不合并HTG患者的脂质谱、葡萄糖稳态参数、合并症、无心血管事件的5年生存率。初步评估后，将107例VHRH患者分为两组，即无HTG组(n=49)和有HTG组(n=58)。在观察期间，每年对患者进行一次关于既往住院情况的访谈，并进一步筛查糖尿病。联合终点包括因急性心肌梗死、失代偿性心力衰竭、中风或死亡而住院。采用Kaplan-Meier法分析生存率。采用非参数方法进行统计分析。2组甘油三酯-高密度脂蛋白胆固醇比值、脂质积累产物、空腹胰岛素和HOMA指数的对数值中位数较高(P< 0.002)，反映了小密度LDL颗粒、异位脂质沉积和胰岛素抵抗的优势。HTG患者更常见于2型糖尿病(58.6% vs 34.5%，包括在初始评估和观察中首次发现的病例，P=0.02)、肝脂肪变性(81.0% vs 55.1%， P=0.006)和结石性胆囊疾病(55.2% vs 34.7%， P=0.05)。HTG患者常有子宫切除术史(55.2% vs 19.0%， Р =0.018)。尽管长期接受他汀类药物治疗，但他们往往无法达到推荐的LDL-C目标，并且由于复合终点的发生率明显较高(39.6% vs 22.4%， P=0.027)，生存率较差。在这一人群中寻找安全有效的二级预防策略需要进一步的研究。
{"title":"Hypertriglyceridemia is associated with long-term risk of cardiovascular events and specific comorbidity in very high-risk hypertensive patients","authors":"Ya Danylo, Halytskyi Lviv, Korolyuk O Ya","doi":"10.15407/ubj92.02.008","DOIUrl":"https://doi.org/10.15407/ubj92.02.008","url":null,"abstract":"Although hypertriglyceridemia (HTG) frequently occurs in hypertensive patients and may increase cardiovascular risk, the need and way of its reduction remain controversial. The objectives of the research was to compare lipid profiles, parameters of glucose homeostasis, comorbidity, a 5-year survival without cardiovascular events in very high risk hypertensive (VHRH) patients with and without HTG, who received moderate intensity atorvastatin therapy. After initial assessment 107 VHRH subjects were divided into two groups, i.e., without (n=49) and with HTG (n=58). During observation once annually patients were interviewing about prior hospitalizations with further screening for diabetes. Combined endpoint included hospitalization due acute myocardial infarction, decompensated heart failure, stroke or death. Survival was analyzed by Kaplan-Meier’s method. Nonparametric methods were used for statistical analysis. Higher median values of logarithmic value of triglycerides-to-HDL-cholesterol ratio, lipid accumulation product, fasting insulin, and HOMA index were observed in group 2 ( P< 0.002) that reflect predominance of small dense LDL particles, ectopic lipid deposition and insulin resistance. Patients with HTG more commonly had type 2 diabetes (58.6% vs 34.5%, including first-detected cases during initial assessments and observation, P=0.02), liver steatosis (81.0% vs 55.1%, P=0.006), and lithogenic gallbladder disorders (55.2% vs 34.7%, P=0.05). Women with HTG frequently had a history of hysterovariectomy (55.2% vs 19.0%, Р =0.018). Despite long-term statin therapy, they often failed to reach recommended LDL-C targets and had worse survival due to significantly higher incidence of composite endpoint (39.6% vs 22.4%, P=0.027). Further researches are necessary to find safe and effective strategy for secondary prevention in this population.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67022028","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. Finiuk, Y. Ostapiuk, V. Hreniukh, Ya. R. Shalai, V. Matiychuk, M. Obushak, R. Stoika, A. Babsky
The research aim was to test cytotoxic effects in vitro of seven novel pyrazolothiazolopyrimidine derivatives in targeting several lines of tumor and pseudo-normal mammalian cells. We demonstrated that cytotoxic effects of these derivatives depended on the tissue origin of targeted cells. Leukemia cells were found to be the most sensitive to the action of compounds 2 and 7. Compound 2 demonstrated approximately two times higher toxicity towards the multidrug-resistant sub-line of HL-60/ADR cells compared to the Doxorubicin effect. Antiproliferative action of compounds 2 and 7 dropped in the order: leukemia > melanoma > hepatocarcinoma > glioblastoma > colon carcinoma > breast and ovarian carcinoma cells. These compounds were less toxic than Doxorubicin towards the non-tumor cells. The novel pyrazolothiazolopyrimidine, compound 2, demonstrated high toxicity towards human leukemia and, of special importance, towards multidrug-resistant leukemia cells, and low toxicity towards pseudo-normal cells.
{"title":"Evaluation of antiproliferative activity of pyrazolothiazolopyrimidine derivatives","authors":"N. Finiuk, Y. Ostapiuk, V. Hreniukh, Ya. R. Shalai, V. Matiychuk, M. Obushak, R. Stoika, A. Babsky","doi":"10.15407/UBJ90.02.025","DOIUrl":"https://doi.org/10.15407/UBJ90.02.025","url":null,"abstract":"The research aim was to test cytotoxic effects in vitro of seven novel pyrazolothiazolopyrimidine derivatives in targeting several lines of tumor and pseudo-normal mammalian cells. We demonstrated that cytotoxic effects of these derivatives depended on the tissue origin of targeted cells. Leukemia cells were found to be the most sensitive to the action of compounds 2 and 7. Compound 2 demonstrated approximately two times higher toxicity towards the multidrug-resistant sub-line of HL-60/ADR cells compared to the Doxorubicin effect. Antiproliferative action of compounds 2 and 7 dropped in the order: leukemia > melanoma > hepatocarcinoma > glioblastoma > colon carcinoma > breast and ovarian carcinoma cells. These compounds were less toxic than Doxorubicin towards the non-tumor cells. The novel pyrazolothiazolopyrimidine, compound 2, demonstrated high toxicity towards human leukemia and, of special importance, towards multidrug-resistant leukemia cells, and low toxicity towards pseudo-normal cells.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"90 1","pages":"25-32"},"PeriodicalIF":0.0,"publicationDate":"2018-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41409244","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. Hudz, L. Kobylinska, N. Dmytrukha, R. Korytniuk, P. Wieczorek
the purpose of our work was to conduct biological and analytical studies of the peritoneal dialysis (Pd) solutions containing glucose and sodium lactate and establish correlations between cell viability of the Vero cell line and values of analytical indexes of the tested solutions. The results of this study confirm the cytotoxicity of the Pd solutions even compared with the isotonic solution of sodium chloride, which may be due to the low pH of the solutions, presence of glucose degradation products (GdPs) and high osmolarity of the solutions, and unphysiological concentrations of glucose and sodium lactate. However, it is not yet known what factors or their combination and to what extent cause the cytotoxicity of Pd solutions. In the neutral red (Nr) test the weak, almost middle (r = -0.496 and 0.498, respectively) and unexpected correlations were found between reduced viability of monkey kidney cells and increased pH of the Pd solutions and between increased cell viability and increased absorbance at 228 nm of the tested Pd solutions. these two correlations can be explained by a strong correlation (r = -0.948) between a decrease in pH and an increase in the solution absorbance at 228 nm. The opposite effect was observed in the MTT test. The weak, but expected correlations (r = 0.32 and -0.202, respectively) were found between increased cell viability and increased pH in the Pd solutions and between decreased cell viability and increased absorbance at 228 nm of the tested Pd solutions. the middle and weak correlations (r = 0.56 and 0.29, respectively) were detected between increased cell viability and increased lactate concentration in the Nr test and mtt test. the data of these correlations can be partially explained by the fact that a correlation with a coefficient r = -0.34 was found between decreased pH in the solutions and increased lactate concentration. the very weak correlations (0.138 and 0.196, respectively) were found between increased cell viability and increased glucose concentration in the Nr test and mtt test. these experimental data indicate that pH is the dominating factor, which determines almost all of the established correlations. However, the character of the correlations is quite different: the higher the pH, the greater was the cell viability in the mtt test, and conversely, the higher the pH, the lower was the cell viability in the NR test. Secondly, the unexpected correlation coefficient was determined as -0.473 between decreased cell viability in the mtt test and increased cell viability in the Nr test. moreover, this phenomenon indicates that the mitochondrial enzyme succinate dehydrogenase is more vulnerable to the action of Pd solutions than membrane permeability. Finally, we conclude that the Nr test is not suitable for comparative studies of Pd solutions which differ in pH, as it is pH dependent and does not enable the comparison of plausible cell viability.
{"title":"Biological and analytical studies of peritoneal dialysis solutions","authors":"N. Hudz, L. Kobylinska, N. Dmytrukha, R. Korytniuk, P. Wieczorek","doi":"10.15407/UBJ90.02.034","DOIUrl":"https://doi.org/10.15407/UBJ90.02.034","url":null,"abstract":"the purpose of our work was to conduct biological and analytical studies of the peritoneal dialysis (Pd) solutions containing glucose and sodium lactate and establish correlations between cell viability of the Vero cell line and values of analytical indexes of the tested solutions. The results of this study confirm the cytotoxicity of the Pd solutions even compared with the isotonic solution of sodium chloride, which may be due to the low pH of the solutions, presence of glucose degradation products (GdPs) and high osmolarity of the solutions, and unphysiological concentrations of glucose and sodium lactate. However, it is not yet known what factors or their combination and to what extent cause the cytotoxicity of Pd solutions. In the neutral red (Nr) test the weak, almost middle (r = -0.496 and 0.498, respectively) and unexpected correlations were found between reduced viability of monkey kidney cells and increased pH of the Pd solutions and between increased cell viability and increased absorbance at 228 nm of the tested Pd solutions. these two correlations can be explained by a strong correlation (r = -0.948) between a decrease in pH and an increase in the solution absorbance at 228 nm. The opposite effect was observed in the MTT test. The weak, but expected correlations (r = 0.32 and -0.202, respectively) were found between increased cell viability and increased pH in the Pd solutions and between decreased cell viability and increased absorbance at 228 nm of the tested Pd solutions. the middle and weak correlations (r = 0.56 and 0.29, respectively) were detected between increased cell viability and increased lactate concentration in the Nr test and mtt test. the data of these correlations can be partially explained by the fact that a correlation with a coefficient r = -0.34 was found between decreased pH in the solutions and increased lactate concentration. the very weak correlations (0.138 and 0.196, respectively) were found between increased cell viability and increased glucose concentration in the Nr test and mtt test. these experimental data indicate that pH is the dominating factor, which determines almost all of the established correlations. However, the character of the correlations is quite different: the higher the pH, the greater was the cell viability in the mtt test, and conversely, the higher the pH, the lower was the cell viability in the NR test. Secondly, the unexpected correlation coefficient was determined as -0.473 between decreased cell viability in the mtt test and increased cell viability in the Nr test. moreover, this phenomenon indicates that the mitochondrial enzyme succinate dehydrogenase is more vulnerable to the action of Pd solutions than membrane permeability. Finally, we conclude that the Nr test is not suitable for comparative studies of Pd solutions which differ in pH, as it is pH dependent and does not enable the comparison of plausible cell viability.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"90 1","pages":"34-44"},"PeriodicalIF":0.0,"publicationDate":"2018-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45088451","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}
Yu. S. Kozak, R. Panchuk, N. Skorokhyd, L. V. Lehka, R. Stoika
N-acetylcysteine (NAC) is a dietary supplement demonstrating antioxidant and liver protecting effects that is widely used in clinics. NAC is considered to possess potential therapeutic activity for health disorders characterized by generation of free oxygen radicals, as well as potential for decreasing negative side effects of various drugs. However, the mechanisms of such tissue-protective actions of NAC remain poorly understood. The main aim of this work was to study therapeutic effects of NAC applied together with the “gold standard” of chemotherapy doxorubicin (Dx) or the novel experimental drug landomycin A (LA) to mice bearing NK/Ly lymphoma. It was revealed that NAC significantly decreased the nephrotoxicity of Dx (measured as creatinine level), possessed moderate immunomodulating activity (as revealed by an increase in number of cytotoxic T-lymphocytes), and partially increased survival of NK/Ly lymphoma-bearing animals treated with Dx. On the contrary, there was little tissue-protective effect of NAC towards LA due to the weak side effects of this anticancer drug, however, the combined use of NAC and LA significantly increased survival (60+ days) of LAtreated animals with NK/Ly lymphoma. Summarizing, NAC possesses a moderate tissue-protective activity towards Dx action but lacks a major therapeutic effect. However, in the case of LA action, NAC significantly increases its anticancer activity with no impact on its negative side effects. Further studies of the molecular mechanisms underlying that activity of NAC towards the action of LA are in progress.
n -乙酰半胱氨酸(NAC)是一种膳食补充剂，具有抗氧化和保护肝脏的作用，被广泛应用于临床。NAC被认为对以产生自由基为特征的健康疾病具有潜在的治疗活性，并具有减少各种药物副作用的潜力。然而，NAC的这种组织保护作用的机制仍然知之甚少。本研究的主要目的是研究NAC与“金标准”化疗药物阿霉素(Dx)或新型实验药物陆霉素A (LA)联合应用对NK/Ly淋巴瘤小鼠的治疗效果。结果表明，NAC显著降低了Dx的肾毒性(以肌酐水平测量)，具有中等的免疫调节活性(通过细胞毒性t淋巴细胞数量的增加显示)，并部分提高了NK/Ly淋巴瘤携带动物的存活率。相反，由于LA的副作用较弱，NAC对LA的组织保护作用不大，但NAC和LA联合使用可显著提高NK/Ly淋巴瘤治疗动物的生存期(60+天)。综上所述，NAC对Dx作用具有适度的组织保护活性，但缺乏主要的治疗作用。然而，在LA作用的情况下，NAC显著增加了其抗癌活性，而对其负面副作用没有影响。NAC对LA作用的分子机制的进一步研究正在进行中。
{"title":"Impact of N-acetylcysteine on antitumor activity of doxorubicin and landomycin A in NK/Ly lymphoma-bearing mice","authors":"Yu. S. Kozak, R. Panchuk, N. Skorokhyd, L. V. Lehka, R. Stoika","doi":"10.15407/UBJ90.02.046","DOIUrl":"https://doi.org/10.15407/UBJ90.02.046","url":null,"abstract":"N-acetylcysteine (NAC) is a dietary supplement demonstrating antioxidant and liver protecting effects that is widely used in clinics. NAC is considered to possess potential therapeutic activity for health disorders characterized by generation of free oxygen radicals, as well as potential for decreasing negative side effects of various drugs. However, the mechanisms of such tissue-protective actions of NAC remain poorly understood. The main aim of this work was to study therapeutic effects of NAC applied together with the “gold standard” of chemotherapy doxorubicin (Dx) or the novel experimental drug landomycin A (LA) to mice bearing NK/Ly lymphoma. It was revealed that NAC significantly decreased the nephrotoxicity of Dx (measured as creatinine level), possessed moderate immunomodulating activity (as revealed by an increase in number of cytotoxic T-lymphocytes), and partially increased survival of NK/Ly lymphoma-bearing animals treated with Dx. On the contrary, there was little tissue-protective effect of NAC towards LA due to the weak side effects of this anticancer drug, however, the combined use of NAC and LA significantly increased survival (60+ days) of LAtreated animals with NK/Ly lymphoma. Summarizing, NAC possesses a moderate tissue-protective activity towards Dx action but lacks a major therapeutic effect. However, in the case of LA action, NAC significantly increases its anticancer activity with no impact on its negative side effects. Further studies of the molecular mechanisms underlying that activity of NAC towards the action of LA are in progress.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"90 1","pages":"46-54"},"PeriodicalIF":0.0,"publicationDate":"2018-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41959901","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}
D. Labudzynskyi, І. О. Shymanskyi, O. Lisakovska, М. М. Veliky
{"title":"Osteoprotective effects of vitamin D(3) in diabetic mice is VDR-mediated and regulated via RANKL/RANK/OPG axis","authors":"D. Labudzynskyi, І. О. Shymanskyi, O. Lisakovska, М. М. Veliky","doi":"10.15407/UBJ90.02.056","DOIUrl":"https://doi.org/10.15407/UBJ90.02.056","url":null,"abstract":"","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"90 1","pages":"56-65"},"PeriodicalIF":0.0,"publicationDate":"2018-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48846363","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}
I. I. Patalakh, O. V. Revka, O. Kuchmenko, O. Matova, T. Drobotko, T. Grinenko
Hemostatic balance in blood is affected by numerous factors, including coagulation and fibrinolytic proteins, the wide spectrum of their inhibitors, and blood cells. Since platelets can participate in contradictory processes, they significantly complicate the whole picture. Therefore, nowadays the development of global assays of hemostasis, which can reflect the physiological process of hemostasis and can be used for point-of-care diagnosis of thrombosis, is crucial. This paper outlines a new approach we used to analyze the capabilities of clot waveform analysis tools to distinguish the response of platelet-rich plasma from healthy donors and patients with arterial hypertension caused by stimulation of coagulation and lysis (with exogenous thrombin and recombinant tissue-type plasminogen activator, respectively). In donor plasma, when the clot degradation was accompanied by 40 IU/ml of recombinant tissue-type plasminogen activator, platelets potentiated fibrinolysis more than coagulation, which ultimately shifts the overall balance to a profibrinolytic state. at the same time, for patients with hypertension, platelets, embedded in clot obtained from platelet-rich plasma, showed a weaker ability to stimulate fibrinolysis. The obtained data gives the evidence that platelets can act not only as procoagulants but also as profibrinolytics. By simultaneously amplifying coagulation and fibrinolysis, making their rates comparable, platelets would control plasma procoagulant activity, thereby regulating local hemostatic balance, the size and lifetime of the clot. Moreover, clot waveform analysis may be used to distinguish the effects of platelet-rich plasma on clotting or lysis of fibrin clots in healthy donors and patients with essential hypertension.
{"title":"Clot formation and lysis in platelet rich plasma of healthy donors and patients with resistant hypertension","authors":"I. I. Patalakh, O. V. Revka, O. Kuchmenko, O. Matova, T. Drobotko, T. Grinenko","doi":"10.15407/UBJ90.02.067","DOIUrl":"https://doi.org/10.15407/UBJ90.02.067","url":null,"abstract":"Hemostatic balance in blood is affected by numerous factors, including coagulation and fibrinolytic proteins, the wide spectrum of their inhibitors, and blood cells. Since platelets can participate in contradictory processes, they significantly complicate the whole picture. Therefore, nowadays the development of global assays of hemostasis, which can reflect the physiological process of hemostasis and can be used for point-of-care diagnosis of thrombosis, is crucial. This paper outlines a new approach we used to analyze the capabilities of clot waveform analysis tools to distinguish the response of platelet-rich plasma from healthy donors and patients with arterial hypertension caused by stimulation of coagulation and lysis (with exogenous thrombin and recombinant tissue-type plasminogen activator, respectively). In donor plasma, when the clot degradation was accompanied by 40 IU/ml of recombinant tissue-type plasminogen activator, platelets potentiated fibrinolysis more than coagulation, which ultimately shifts the overall balance to a profibrinolytic state. at the same time, for patients with hypertension, platelets, embedded in clot obtained from platelet-rich plasma, showed a weaker ability to stimulate fibrinolysis. The obtained data gives the evidence that platelets can act not only as procoagulants but also as profibrinolytics. By simultaneously amplifying coagulation and fibrinolysis, making their rates comparable, platelets would control plasma procoagulant activity, thereby regulating local hemostatic balance, the size and lifetime of the clot. Moreover, clot waveform analysis may be used to distinguish the effects of platelet-rich plasma on clotting or lysis of fibrin clots in healthy donors and patients with essential hypertension.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"90 1","pages":"67-75"},"PeriodicalIF":0.0,"publicationDate":"2018-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48303382","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. Paryzhak, T. Dumych, O. Karmash, E. Bila, D. Stachowiak, M. Bański, A. Podhorodecki, R. Bilyy
covering of nanocrystals (Nc) with a polyethylene glycol (PEG) envelop is a common way to increase their hydrophilicity, and compatibility with bio-systems, including increased retention time in the body. colloidal semiconductor NC, also known as quantum dots (QD), particularly benefit from covering with PEG due to passivation of the inorganic core, while maintaining physical properties of the core. Despite many advantages of covering the surface with PEG, the covalent attachment of protein to hydroxyls of PEG is complicated. Here we propose a simple two-step approach for modification of PEG residues with subsequent covalent attachment of proteins. We were able to achieve specific NC targeting by means of attached protein as well as preserve their optical parameters (fluorescence intensity) in chemical reaction conditions. In the optimized protocol, ensuring removal of chemical byproducts by dialysis, we were able to omit the need for centrifugation (usually a limiting step due to particle size). The obtained Nc-protein conjugate solutions contained 0.25x of initial unmodified NC amount, ensuring a low dilution of the sample. During all reactions the pH range was optimized to be between 6 to 8. The proposed approach can be easily modified for covalent targeting of different PEG-covered nanocomposites with proteins.
{"title":"Simple two-step covalent protein conjugation to PEG-coated nanocrystals","authors":"S. Paryzhak, T. Dumych, O. Karmash, E. Bila, D. Stachowiak, M. Bański, A. Podhorodecki, R. Bilyy","doi":"10.15407/UBJ90.02.008","DOIUrl":"https://doi.org/10.15407/UBJ90.02.008","url":null,"abstract":"covering of nanocrystals (Nc) with a polyethylene glycol (PEG) envelop is a common way to increase their hydrophilicity, and compatibility with bio-systems, including increased retention time in the body. colloidal semiconductor NC, also known as quantum dots (QD), particularly benefit from covering with PEG due to passivation of the inorganic core, while maintaining physical properties of the core. Despite many advantages of covering the surface with PEG, the covalent attachment of protein to hydroxyls of PEG is complicated. Here we propose a simple two-step approach for modification of PEG residues with subsequent covalent attachment of proteins. We were able to achieve specific NC targeting by means of attached protein as well as preserve their optical parameters (fluorescence intensity) in chemical reaction conditions. In the optimized protocol, ensuring removal of chemical byproducts by dialysis, we were able to omit the need for centrifugation (usually a limiting step due to particle size). The obtained Nc-protein conjugate solutions contained 0.25x of initial unmodified NC amount, ensuring a low dilution of the sample. During all reactions the pH range was optimized to be between 6 to 8. The proposed approach can be easily modified for covalent targeting of different PEG-covered nanocomposites with proteins.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"90 1","pages":"8-12"},"PeriodicalIF":0.0,"publicationDate":"2018-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43293542","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}
Obesity is an important factor in pathogenesis of disorders caused by chronic inflammation. Diet-induced obesity leads to dyslipidemia and insulin resistance (Ir) that in turn provoke the development of type 2 diabetes and cardiovascular diseases. thus, the aim of this work was to investigate the possible pro-atherogenic effects in the blood coagulation system and aortic wall of rats with obesity-induced IR. The experimental model was induced by a 6-month high-fat diet (hFD) in white rats. Blood samples were collected from 7 control and 14 obese Ir rats. Prothrombin time (Pt) and partial activated thromboplastin time (aPtt) were performed by standard methods using Coagulometer Solar СТ 2410. Fibrinogen concentration in the blood plasma was determined by the modified spectrophotometric method. Levels of protein C (PC), prothrombin and factor X were measured using specific chromogenic substrates and activa ting enzymes from snake venoms. Platelet aggregation was measured and their count determined using aggregometer Solar aP2110. the aorta samples were stained by hematoxylin and eosin according to Ehrlich. Aortic wall thickness was measured using morphometric program Image J. Statistical analysis was performed using Mann-Whitney U test. the haemostasis system was characterized by estimation of the levels of individual coagulation factors, anticoagulant system involvement and platelet reactivity. Pt and aPtt demonstrated that blood coagulation time strongly tended to decrease in obese Ir rats in comparison to the control group. It was also detec ted that 30% of studied obese IR rats had decreased factor X level, 40% had decreased level of prothrombin whereas fibrinogen concentration was slightly increased up to 3 mg/ml in 37% of obese Ir rats. a prominent decrease of anticoagulant PC in blood plasma of obese rats was detected. Obese Ir rats also had increased platelet count and higher rate of platelet aggregation in comparison to control animals. Histological analysis identified the disruption of aorta endothelium and tendency for the thickening of the aorta wall in the group with obesityinduced Ir compared to the group of control rats. Changes of individual coagulation factors were assumed as the evidence of imbalance in the blood coagulation system. Increase of fibrinogen level, drop in PC concentration and pathological platelet reactivity were taken to corroborate the development of low-grade inflammation in obese IR rats. Instant generation of small amounts of thrombin in their blood plasma is expected. Since the aorta morphology assay detected the trend of its wall to thicken and the emergence of disruptions, we assumed there were initial stages of atherosclerosis and the danger of developing atherothrombosis. We detected an increase of blood coagulability and changes in aorta morphology in rats with obesity-induced Ir which we assume indicate early development of atherosclerosis.
{"title":"Blood coagulation and aortic wall integrity in rats with obesity-induced insulin resistance","authors":"O. Dziuba","doi":"10.15407/UBJ90.02.014","DOIUrl":"https://doi.org/10.15407/UBJ90.02.014","url":null,"abstract":"Obesity is an important factor in pathogenesis of disorders caused by chronic inflammation. Diet-induced obesity leads to dyslipidemia and insulin resistance (Ir) that in turn provoke the development of type 2 diabetes and cardiovascular diseases. thus, the aim of this work was to investigate the possible pro-atherogenic effects in the blood coagulation system and aortic wall of rats with obesity-induced IR. The experimental model was induced by a 6-month high-fat diet (hFD) in white rats. Blood samples were collected from 7 control and 14 obese Ir rats. Prothrombin time (Pt) and partial activated thromboplastin time (aPtt) were performed by standard methods using Coagulometer Solar СТ 2410. Fibrinogen concentration in the blood plasma was determined by the modified spectrophotometric method. Levels of protein C (PC), prothrombin and factor X were measured using specific chromogenic substrates and activa ting enzymes from snake venoms. Platelet aggregation was measured and their count determined using aggregometer Solar aP2110. the aorta samples were stained by hematoxylin and eosin according to Ehrlich. Aortic wall thickness was measured using morphometric program Image J. Statistical analysis was performed using Mann-Whitney U test. the haemostasis system was characterized by estimation of the levels of individual coagulation factors, anticoagulant system involvement and platelet reactivity. Pt and aPtt demonstrated that blood coagulation time strongly tended to decrease in obese Ir rats in comparison to the control group. It was also detec ted that 30% of studied obese IR rats had decreased factor X level, 40% had decreased level of prothrombin whereas fibrinogen concentration was slightly increased up to 3 mg/ml in 37% of obese Ir rats. a prominent decrease of anticoagulant PC in blood plasma of obese rats was detected. Obese Ir rats also had increased platelet count and higher rate of platelet aggregation in comparison to control animals. Histological analysis identified the disruption of aorta endothelium and tendency for the thickening of the aorta wall in the group with obesityinduced Ir compared to the group of control rats. Changes of individual coagulation factors were assumed as the evidence of imbalance in the blood coagulation system. Increase of fibrinogen level, drop in PC concentration and pathological platelet reactivity were taken to corroborate the development of low-grade inflammation in obese IR rats. Instant generation of small amounts of thrombin in their blood plasma is expected. Since the aorta morphology assay detected the trend of its wall to thicken and the emergence of disruptions, we assumed there were initial stages of atherosclerosis and the danger of developing atherothrombosis. We detected an increase of blood coagulability and changes in aorta morphology in rats with obesity-induced Ir which we assume indicate early development of atherosclerosis.","PeriodicalId":23448,"journal":{"name":"Ukrainian Biochemical Journal","volume":"90 1","pages":"14-23"},"PeriodicalIF":0.0,"publicationDate":"2018-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42058796","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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