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The effect of quercetin on oxidative stress markers and mitochondrial permeability transition in the heart of rats with type 2 diabetes

N. I. Gorbenko1, O. Yu. Borikov2, O. V. Ivanova1, E. V. Taran1,
Т. S. Litvinova1, T. V. Kiprych1, A. S. Shalamai3

1V. Danilevsky Institute of Endocrine Pathology Problems, National Academy of Medical Sciences of Ukraine, Kharkiv;
2V. N. Karazin Kharkiv National University, Ukraine;
3PJSC SIC “Borshchahivskiy Chemical-Pharmaceutical Plant”, Kyiv, Ukraine;
е-mail: Gorbenkonat58@ukr.net

Received: 24 June 2019; Accepted: 13 August 2019

Increasing evidence suggests that oxidative stress and induction of mitochondrial permeability transition in cardiomyocytes are linked to tissue damage and the development of diabetic cardiovascular complications. The aim of this study was to assess the effects of quercetin (Q) on oxidative stress and mitochondrial permeability transition in the heart of rats with type 2 diabetes mellitus (DM). Type 2 DM was induced in 12-week-old male Wistar rats by intraperitoneal injections of 25 mg/kg streptozotocin twice per week followed by a high-fat diet during four weeks. The rats were divided into three groups: control intact group (C, n = 8), untreated diabetic group (Diabetes, n = 8) and diabetic rats treated with Q (50 mg/kg/day per os for 8 weeks) after diabetes induction (Diabetes+Q, n = 8). Administration of Q increased insulin sensitivity and normali­zed the functional state of cardiac mitochondria due to increased aconitase and succinate dehydrogenase activities in rats with type 2 DM. Q also ameliorated oxidative stress, decreasing the level of advanced oxidation protein products and increasing the activity of thioredoxin-reductase in heart mitochondria of diabetic rats. In addition, Ca2+-induced opening of the mitochondrial permeability transition pore was significantly inhibited in diabetic rats treated with Q in comparison with the untreated diabetic group. These data demonstrate that Q can protect against oxidative stress, mitochondrial permeability transition induction and mitochondrial dysfunction in cardiomyocytes of diabetic rats. We suggest that the use of Q may contribute to the amelioration of cardiovascular risk in type 2 DM.

Brownian motion, electrophoresis, chromatography, and macromolecular chemistry: how it all unites Nobel laureates of the first half of the 20th century – T. Svedberg, A. Tiselius, R. Synge and H. Staudinger

M. V. Grigorieva, V. M. Danilova, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kуiv;
e-mail: mvgrigorieva@biochem.kiev.ua

Received: 31 July 2019; Accepted: 13 August 2019

It is hard to imagine how chemistry, biology and medicine would develop without such techniques as ultracentrifugation, electrophoresis and chromatography. At present innovative hi-tech laboratory ultracentrifuges are widely used in various fields of fundamental science and practice, including colloid chemistry, biochemical analysis, virology, clinical diagnostics, pharmacy, nanotechnology, to name a few. Electrophoresis enables to detect protein abnormalities with high probability, and, therefore, has wide application for the diagnosis of infectious-inflammatory diseases, genetic and immune disorders, malignant tumors and others. Chromatography is widely used for biochemical research and analytical detection and control of drugs and food. But where did these methods, which have had a significant impact on the development of various­ fields of scientific and economic activity, come from? Who were the pioneers in this field and whose work influenced the formation of the next generation of researchers? These are the questions we address in this article.

Alpha-fetoprotein as a biochemical diagnostic and prognostic marker for prolonged jaundice in newborns

O. H. Mazur, O. S. Yablon, O. S. Rubina,
M. M. Puhach, A. P. Konoplitska

National Pirogov Memorial Medical University, Vinnytsia, Ukraine;
e-mail: alena523@ukr.net

Received: 14 January 2019; Accepted: 13 August 2019

Prolonged jaundice of newborns is a common pathology during the neonatal period. Recently, there has been a tendency toward an increased number of newborns with prolonged jaundice with duration longer than 14 days of life. According to the polyetiologic nature of neonatal jaundice, it is necessary to investigate new diagnostic signs that can predict the development of prolonged jaundice in newborns and, allow identification of new methods of differential diagnosis of neonatal jaundice, as well as decrease the frequency of this pathology. The parameters of serum alpha-fetoprotein (AFP) content in newborns with prolonged jaundice were studied. The content of AFP in blood serum was 1.7 times higher in newborns with prolonged jaundice than in newborns with jaundice for up to 14 days of life: Me = 671.1 [Q1 = 479.9; Q3 = 815.03] ng/ml and Me = 401.0 [Q1 = 284.9; Q3 = 684.0] ng/ml, respectively (P < 0.05). The content of blood serum AFP in newborns with prolonged jaundice was higher for total serum bilirubin greater than 250 μmole/l: Me = 626.2 [Q1 = 454.7; Q3 = 793.2] ng/ml which was confirmed by a strong direct correlation relationship (rxy = 0.64, P < 0.05). The results of the ROC analysis confirmed that AFP ≥ 571.7 ng/ml can identify newborns with prolonged jaundice with a sensitivity of 74.2% and a specificity of 74.5%. The area under the curve (AUC) was 0.870 (95% CI 0.804, 0.937), which confirms the good quality of the AFP model ≥ 571.7 ng/ml.

The role of resistin in the genesis of metabolic disorders in pathological pregnancy

S. O. Ostafiichuk

Ivano-Frankivsk National Medical University, Ukraine;
e-mail: svitlana.ostafijchuk@gmail.com

Received: 12 March 2019; Accepted: 13 August 2019

Pathological gestational weight gain (GWG) is a risk factor for obstetric and perinatal complications. High metabolic activity of adipose tissue and the placenta during pregnancy manifests as an increased production of adipokines that are involved in glucose regulation and insulin sensitivity. The aim of this study was to determine the role of resistin in the genesis of metabolic disorders in pathological GWG pregnancies. The 163 pregnant women were examined in the study: 97 (59.5%) had normal, 18 (11.0%) had insufficient and 48 (29.4%) had excessive prepregnancy weight and obesity. GWG was the recommended level in 56 (34.4%), insufficient in 33 (20.2%), and excessive in 74 (45.4%) women. Anthropometry was performed in each trimester of pregnancy, the weight gain was measured, and the percentage of body fat mass, concentrations of resistin, glucose, insulin, and the HOMA-IR were evaluated. Positive associations were found between hyperresis­tinemia in the second trimester of pregnancy, and subsequent weight gain (r = 0.27, P = 0.0006), percentage of body fat mass (r = 0.93, P = 0.000) and insulin resistance (r = 0.89, P = 0.000) in late pregnancy; these associations were especially evident in excessive GWG. Determination of predictors of insulin resistance, associated with endocrine activity of adipose tissue, such as the adipokine resistin, in the second trimester of pregnancy may help to predict the severity of metabolic shifts during pregnancy and the risk of developing obstetric and perinatal complications.

Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke

A. A. Tykhomyrov1, Yu. S. Kushnir2, V. S. Nedzvetsky3,
T. V. Grinenko1, O. V. Kuryata2

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2State Establishment “Dnipropetrovsk Medical Academy of Health Ministry of Ukraine”, Dnipro;
3Bingöl University, Bingöl, Turkey;
e-mail: artem_tykhomyrov@ukr.net

Received: 22 May 2019; Accepted: 13 August 2019

Ischemic stroke is considered as one of the most frequent and severe complications of atrial fibrillation. The present study was undertaken to examine whether post-insult treatment with cytidine diphosphate-choline (CDP-choline, or citicoline) affects serum levels of the angiogenesis inhibitor angiostatin and neurospecific proteins as markers of brain damage in patients with cerebral ischemia associated with atrial fibrillation. Thirty-three patients with a diagnosis of acute ischemic stroke received citicoline sodium by intravenous infusions (1,000 mg daily for 14 days) in addition to the standard treatment (basic group). Twenty-five patients with the same pathologies, who received only standard therapy, were enrolled in the study as a control group. Serum content of angiostatin and neurospecific proteins, namely neurofilament heavy subunit (NF-H) and glial fibrillary acidic protein (GFAP), was measured by immunoblotting at the basal level and after the treatment. Citicoline treatment caused significant decreases in serum levels of angiostatin (by 40% vs. basal level, P < 0.05), GFAP (by 61%, P < 0.01), and the NF-H subunit (by 19%, P < 0.05) and had no effect on the serum albumin content. In contrast, there were no statistically significant differences between baseline levels of the studied protein markers and their content after the treatment period in the control group. These findings indicate for the first time that CDP-choline protects both astrocytes and neurons and improves angiogenic capacity through down-regulation of angiostatin in post-ischemic patients with atrial fibrillation after acute ischemic stroke. Further studies are needed to test associations between serum levels of these biomarkers, clinical outcomes, and treatment efficacy of stroke.

Influence of human HB-EGF secreted form on cells with different EGFR and ErbB4 quantity

O. I. Krynina, N. V. Korotkevych, A. J. Labyntsev,
S. I. Romaniuk, D. V. Kolybo, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: olyakrynina@gmail.com

Received: 18 July 2019; Accepted: 13 August 2019

HB-EGF is one of the most potent ligands of EGFR and ErbB4 receptors. This growth factor plays a pivotal role in many cellular processes, but its effect differs from one cell type to another and remains not fully understood. The aim of this work was to investigate the dependence between the rate of HB-EGF mediated cell proliferation and activation of EGFR and ErbB4 receptors. Therefore, the effects of human recombinant sHB-EGF (rsHB-EGF) on the proliferation of cell lines with different EGFR and ErbB4 quantity and ratio, as well as activation of the MARK-cascade p38 and ERK1/2 (p42/44) kinases, were analyzed. For comparison, a similar study of the effect of native sHB-EGF secreted by human histiocytic lymphoma cells U937 during co-cultivation with different cell lines was performed.
It was proved that cell proliferation in response to sHB-EGF depends not only on the quantity but also on the ratio of EGFR and ErbB4. It was shown that signaling through ErbB4 is associated with activation of p38 kinase and signaling through EGFR associated with activation of ERK1/2 (p42/44) kinase. We assume the existence of two different mechanisms for sHB-EGF-mediated stimulation of cell proliferation, and the simultaneous launch of these mechanisms provides a maximal proliferative response. The results of this study support the feasibility of creating anti-proliferative drugs that target ErbB4.

Agonists of CB1 and NMDA receptors decrease the toxic effect of organophosphorus compound paraoxon on PC12 cells

F. Salem1, F. Bahrami1,2, Z. Bahari2, Z. Jangravi3, S. Najafizadeh-Sari4

1Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;
2Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran;
3Departmentof Biochemistry, Faculty of Medicine, Baqiyatallah University
of Medical Sciences, Tehran, Iran;
4Student’ Research Committee (SRC), Baqiyatallah University of Medical Sciences, Tehran, Iran;
e-mail: f.bahrami@bmsu.ac.ir or farideh_bahrami@yahoo.com

Received: 01 July 2019; Accepted: 13 August 2019

Pharmacological studies allow to suggest that activation of cannabinoid type 1 receptors (CB1) have a neuroprotective role against toxicity induced by organophosphate agents, but the exact mechanisms of this effect as well as interaction with receptors of other types are far from clear. Therefore, the aim of current study was to evaluate the effect of CB1 and NMDA receptors agonists on cell viability and biomarkers of oxidative stress and lipid peroxidation in PC12 cells exposed to paraoxon. PC12 cells were exposed to 100 µm paraoxon as organophosphate agent. Treatments with 1 µM arachidonyl-2′-chloroethylamide (ACEA) as specific agonist of CB1 receptors, 100 µM N-methyl-D-aspartate (NMDA) as agonist of NMDA receptors and 1 µM AM251 as antagonist of CB1 receptors were done. Cell via­bility and biomarkers of oxidative stress were evaluated after 48 h of incubation. The level of CB1 receptor protein was evaluated by Western blotting. It was demonstrated that PC12 cells treatment with paraoxon led to cell viability inhibition, glutathione level, superoxide dismutase and catalase activity reduction, lipid peroxidation intensification and CB1 receptor expression attenuation. Application of ACEA and NMDA was shown to be followed by normalization of these indices. The protective effect of ACEA was abolished when the CB1 receptors antagonist AM251 was applied. The study revealed that application of ACEA and NMDA can protect PC12 cells against paraoxon induced toxicity through antioxidant capacity increment, lipid peroxidation inhibition and enhanced expression of CB1 receptors.

Effect of recombinant human interleukin-7 on Pseudomonas aeruginosa wound infection

S. M. Grigorieva1, D. B. Starosyla1, S. L. Rybalko1,
V. V. Motronenko2, T. M. Lutsenko2,3, O. Yu. Galkin2

1Gromashevsky Institute of Epidemiology and Infectious Diseases,
National Academy of Medical Sciences of Ukraine, Kyiv;
2National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”;
3UA Pro-Pharma LLC, Kyiv, Ukraine;
e-mail: alexfbt@gmail.com

Received: 01 July 2019; Accepted: 13 August 2019

A wide range of interleukin-7 (IL-7) biological effects suggests that application of appropriate preparations in clinical practice will stimulate immunity in patients with lymphocytic exhaustion or autoimmune diseases.  Studies are being conducted for IL-7 based preparations aimed at restoration of the immune system of patients with immunodeficiency of different origins. Pseudomonas aeruginosa is an important pathogen, which causes nosocomial infections in hospitalized patients. Infection factors, affecting the immune status of the host, play a key role. A promising and relevant scientific endeavor is the study of the effect of recombinant IL-7 (rIL-7) as an adjunct therapy in wound infections caused by P. aeruginosa. The aim of this study was to evaluate the effectiveness of rIL-7 use in P. aeruginosa wound infection in mice. The experiments were conducted using a standardized rIL-7 preparation, P. aeruginosa strain and 20 white non-inbred mice. The preparation of rIL-7 after all stages of purification was characterized by the content of ballast proteins and impurities via electrophoresis in a polyacrylamide gel in reducing conditions, and its biological activity was evaluated in the MTT test by means of proliferation of peripheral blood mononuclear cells. In the mice, the fur was removed, the neck nape was intentionally injured and P. aeruginosa bacteria were injected into the wound of each animal (0.1 ml of suspension with a bacterial cell concentration of 0.08×109 cells/ml). Starting from the 2nd day, bacterial examination of the wound material was carried out daily. Starting from the 3rd day, the mice (experimental group, n = 10) were intraperitoneally administered 5 μg (0.1 ml) of the rIL-7 preparation. In the control group of animals (n = 10), the rIL-7 preparation was not administered. In 80% of experimental animals (administered the rIL-7 preparation), the healing of wounds and elimination of the pathogen of purulent inflammatory infection P. aeruginosa occurred on the 7th day. On the 9th day from the beginning of wound infection, wound healing and elimination of P. aeruginosa occurred in all experimental mice. In 60% of mice from the control group (did not receive treatment with rIL-7), wound healing and the elimination of P. aeruginosa occurred on the 9th day. Wound healing and elimination of P. aeruginosa in all mice of the control group occurred on the 14th day. Thus, in mice treated with rIL-7, wound healing and elimination of the pathogen occurred 5 days earlier than in mice from the control group (without rIL-7 treatment). Subsequent studies may be aimed at developing protocols for the treatment of wound infections using an rIL-7 preparation in patients with a compromised immune system Therefore, rIL-7 is a promising preparation for the treatment of complex wound infections.

Joining the global scientific community – UBJ on its way

M. Grigorieva, V. Chernyshenko, S. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: mayagrigorieva@gmail.com

Over the last decade, The Ukrainian Biochemical Journal (UBJ) has taken a number of measures that have allowed it to leave its narrowly domestic past behind and come a step closer to the international community of scientific publications. In the first phase of the UBJ transformation the journal was made English-lingual only, its manuscript handling process was somewhat streamlined, and a brand-new website for the journal was developed. The range of international databases, in which the UBJ was listed, was also significantly extended. The second phase of the UBJ upgrade began in October 2018, when the journal received a grant from the Regional Cooperation for Health, Science and Technology (RECOOP) to implement the project “Scientific communication of RECOOP partners using the UBJ platform”. The project’s objectives include raising the journal’s quality level to international standards, globalizing it, and making it a reliable platform for the RECOOP publishing activity in Eastern Europe by promoting articles within the scope of RECOOP research strategy.

The contribution of the Nobel prize laureates to the development of knowledge of vitamin biochemistry: Ch. Eijkman, F. G. Hopkins, A. Szent-Györgyi, W. Haworth, P. Karrer, R. Kuhn, H. Dam, E. A. Doisy, G. Minot, W. Murphy, G. Whipple, D. Hodgkin, R. Woodward

V. M. Danilova, R. P. Vynogradova, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: valdan@biochem.kiev.ua

In the first half of the 20th century, the experimental research of chemists, biochemists and physiologists in collaboration with doctors led to the discovery of a new class of biologically active compounds – vitamins. Many of these scientists were awarded the Nobel Prizes. Thanks to their efforts, almost all currently known vitamins (B1, B2, B6, B9, B12, C, A, E, K) were identified, their structure and the mechanism of biological action were characteri­zed. Many vitamins were found to serve as coenzymes in important biochemical conversions. This article talks about the history of the discovery of the most familiar vitamins and scientists involved in their research. The contribution made by these distinguished scientists to the development of modern­ biochemical science, in particular, vitaminology, cannot be overestimated.