Molecular mechanisms of the cardiotoxic action of anthracycline antibiotics and statin-induced cytoprotective reactions of cardiomyocytes

2020 ◽  
Vol 66 (5) ◽  
pp. 357-371
Author(s):  
N.V. Tursunova ◽  
M.G. Klinnikova ◽  
O.A. Babenko ◽  
E.L. Lushnikova
Keyword(s):  
Molecular Mechanisms ◽  
Free Radical Oxidation ◽  
Mevalonic Acid ◽  
Acid Synthesis ◽  
Small Gtpase ◽  
Cytostatic Drug ◽  
Rho Proteins ◽  
Anthracycline Antibiotics ◽  
Anthracycline Cardiotoxicity ◽  
Radical Oxidation

The manifestation of the side cardiotoxic effect of anthracycline antibiotics limits their use in the treatment of malignant processes in some patients. The review analyzes the main causes of the susceptibility of cardiomyocytes to the damaging effect of anthracyclines, primarily associated with an increase in the processes of free radical oxidation. Currently, research is widely carried out to find ways to reduce anthracycline cardiotoxicity, in particular, the use of cardioprotective agents in the complex treatment of tumors. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to improve the function and metabolism of the cardiovascular system under various pathological impacts, therefore, it is proposed to use them to reduce cardiotoxic complications of chemotherapy. Statins exhibit direct (hypolipidemic) and pleiotropic effects due to the blockade of mevalonic acid synthesis and downward biochemical cascades that determine their cardioprotective properties. The main point of intersection of the pharmacological activity of anthracyclines and statins is the ability of both to regulate the functioning of small GTPase from the Rho family, and their effect in this regard is the opposite. The influence of statins on the modification and membrane dislocation of Rho proteins mediates the indirect antioxidant, anti-inflammatory, endothelioprotective, antiapoptotic effect. The mechanism of statin inhibition of doxorubicin blockade of the DNA-topoisomerase complex, which may be important in preventing cardiotoxic damage during chemotherapy, is discussed. At the same time, it should be noted that the use of statins can be accompanied by adverse side effects: a provocation of increased insulin resistance and glucose tolerance, which often causes them to be canceled in patients with impaired carbohydrate metabolism, so further studies are needed here. The review also analyzes data on the antitumor effect of statins, their ability to sensitize the tumor to treatment with cytostatic drug. It has been shown that the relationship between anthracycline antibiotics and statins is characterized not only by antagonism, but also in some cases by synergism. Despite some adverse effects, statins are one of the most promising cardio- and vasoprotectors for use in anthracycline cardiomyopathy.

State of the enzyme link of antioxidant protection in boys with hypoandrogenism

2020 ◽  
Vol 40 (4) ◽  
pp. 32-36
Author(s):  
L. K. Parkhomenko ◽  
◽  
L. A. Strashok ◽  
S. I. Turchina ◽  
G. V. Kosovtsova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Glutathione Peroxidase ◽  
Free Radical Oxidation ◽  
Conjugated Dienes ◽  
Delayed Puberty ◽  
Control Group ◽  
Antioxidant Protection ◽  
Radical Oxidation

Recently, interest in the problem of free radical oxidation in biological membranes, which is directly related to both the normal functioning of cells and the occurrence, course and outcome of many pathological conditions, has increased again in clinical medicine. The aim was to determine the role and impact of antioxidant defense in boys with hypoandrogenism. The study involved 75 adolescents with hypoandrogenism aged 13–18 years, who underwent a complex of clinical and laboratory examinations. All patients were conducted complex of anthropometric research and determination of the degree of delayed puberty, laboratory and instrumental examination. Free radical oxidation was determined by the levels of malondialdehyde, conjugated dienes, carbonated proteins, superoxide dismutase and catalase in the serum, and restored glutathione and glutathione peroxidase in whole blood. Based on their determination, the coefficient of oxidative stress was calculated. Statistical processing of results was performed using parametric and nonparametric methods. The study of indicators of the free radical oxidation process found that adolescents with hypoandrogenism have multidirectional changes in the oxidation of proteins and lipids, namely: the level of conjugated dienes increases, the concentration of malondialdehyde remains at the level of the control group, and the level of carbonated proteins tends to decrease. As for the activity of antioxidant protection enzymes, a significant decrease in the level of glutathione peroxidase was detected, while the level of superoxide dismutase and catalase remained at the level of normative indicators. Oxidative stress accompanies and is one of the pathogenetic links in the formation or maintenance of the state of hypoandrogenism in boys. This requires the use of antioxidants, the complex of which must be selected individually.

Adaptogenic correction of free radical brain damage in subchronic exposure to sodium fl uoride

2020 ◽  
pp. 381-386
Author(s):  
A. G. Zhukova ◽  
L. G. Gorokhova ◽  
A. S. Kazitskaya ◽  
T. K. Yadykina ◽  
N. N. Mikhailova ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Free Radical ◽  
Brain Tissue ◽  
Free Radical Oxidation ◽  
Radical Oxidation ◽  
Free Radical Processes ◽  
Subchronic Exposure ◽  
Antioxidant Defense Enzymes ◽  
Radical Processes ◽  
Complex Drug

Introduction. Fluorine compounds in small doses, but with prolonged exposure, cause various disorders in organs at the cellular and molecular levels. Activation of free-radical processes plays an important role in the damaging eff ect of fl uorides. Th erefore, one of the most eff ective ways to limit fl uorine-induced damage is to directly aff ect free-radical processes using herbal preparations with antioxidant properties.The aim of the study is to study the eff ect of a dihydroquercetin-based drug on the activity of free radical processes in brain tissue under subchronic exposure to sodium fl uoride (NaF).Materials and methods. Th e work was performed on white male laboratory rats weighing 200-250 g. Th e rats were divided into 3 groups: 1 — control; 2 — rats with chronic exposure to sodium fl uoride (NaF) for 9 weeks; 3 — rats receiving a NAF solution with simultaneous administration of a complex drug based on dihydroquercetin at a dose of 3 mg/kg in 1% starch gel for 3, 6 and 9 weeks. The activity of free radical oxidation and antioxidant defense enzymes — superoxide dismutase (SOD) and catalase-was determined in the cerebral cortex. Th e level of expression of hypoxia-induced transcription factor HIF — 1A and inducible forms of proteins HSP72 and HSP32 were determined in the cytosolic fraction of brain tissue.Results. In the early stages of subchronic fl uoride exposure (1-3 weeks), the expression of protective proteins HIF-1α, HSP72, HSP32 and catalase was shown in the rat cortex, as a result of which the activity of free-radical processes was maintained at the control level. An increase in the timing of fl uoride intake to 9 weeks led to a decrease in antioxidant protection and signifi cant activation of free radical oxidation in brain tissue. Daily administration of a complex drug with dihydroquercetin for 3, 6 and 9 weeks to rats with subchronic fl uoride exposure led to a decrease in the severity of pro- and antioxidant balance disorders in the cerebral cortex. At the same time, the greatest protective eff ect of dihydroquercetin with fl uoride exposure was manifested by the 9th week of its administration.Conclusions. When subchronic intake of fl uorides in the body, the drug based on dihydroquercetin has a neuroprotective eff ect, which is manifested by an increase in the activity of antioxidant enzymes of fr ee radical oxidation and catalase and the resistance of the cortex to induced fr ee radical oxidation.

Gender differences in biochemical measurement reflecting the state of free-radical oxidation and antioxidant protection among workers in metallurgical production

2019 ◽  
Vol 1 (10) ◽  
pp. 877-881
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Gender Differences ◽  
Free Radical ◽  
Biochemical Parameters ◽  
Free Radical Oxidation ◽  
The Body ◽  
Antioxidant Protection ◽  
Radical Oxidation ◽  
Metallurgical Production ◽  
Production Factors

Introduction. To date, age and sex differences have been established for many biochemical parameters. Gender differences in indicators for systems such as antioxidant, thiol-disulfide, oxidative stress and inflammation systems are absent or under study.The aim of the study was to identify gender differences in biochemical parameters reflecting the functioning of antioxidant systems of the body and free radical oxidation in workers of metallurgical production, in contact with harmful production factors.Materials and methods. The blood of men and women working at the metallurgical enterprise of the Nizhny Novgorod region (n=80) under the influence of a complex of physical and chemical production factors was studied. Total oxidative stress, total antioxidant capacity of serum, glutathione levels were studied by photometric biochemical methods. Levels of C-reactive protein and 8-hydroxy–2-deoxyguanosine were studied by ELISA.Results. The average amount of peroxides in the serum of women exceeded 1.6 times this figure in men. In the group of men, the content of 8-Ondg was higher by 26% (p=0.012), the level of GS-by 12% (p=0.019), the activity of SOD — by 1.5–2 times (p=0.0001), the level of CRP — by 2 times (p=0.008) compared to similar indicators in women.Conclusions. Studies of gender differences in workers under the influence of harmful production factors will allow more effective approach to the etiology, treatment and prognosis of production-related diseases. Indicators of oxidative stress and antioxidant protection can be indicators of the health of workers under the influence of harmful industrial factors and be important in the prevention of diseases associated with oxidative stress.

Assessment of the Biochemical Status of Workers Manufacturing Ethylbenzene and Styrene

2020 ◽  
pp. 40-43
Author(s):  
RR Galimova ◽  
ET Valeeva ◽  
GV Timasheva ◽  
AB Bakirov
Keyword(s):  
Catalase Activity ◽  
Free Radical Oxidation ◽  
The Body ◽  
Atherogenic Index ◽  
Radical Oxidation ◽  
Professional Groups ◽  
Biochemical Status ◽  
The Central Nervous System ◽  
Hepatic Protein Synthesis ◽  
Increased Activity

Introduction: Production of ethylbenzene and styrene (EBS) is one of the most important stages in organic synthesis. The products have general toxic, hepatotoxic, irritating and narcotic effects on the human body. Severe exposures to EВS can induce pronounced disorders of the central nervous system such as styrene sickness and encephalopathy and of peripheral blood such as leukopenia and lymphocytosis. Materials and methods: We studied homeostasis indices in 376 workers of the main professional groups engaged in the production of EBS including equipment operators, repairmen, and instrumentation and automation fitters. Results: We established an increase in lipid peroxidation by the level of malondialdehyde amid an increase in catalase activity and a decrease in blood retinol and α-tocopherol levels. We also noted an increased activity of indicator enzymes including ALT, AST, GGT, and alkaline phosphatase. Significant changes in lipid metabolism in the form of cholesterolemia, triglyceridemia, a higher atherogenic index, and lower cholesterol of non-atherogenic blood serum lipids demonstrating atherogenic changes in the body were revealed. Conclusions: The earliest prenosological disorders in the body of the examined workers included an impaired hepatic protein synthesis, the development of cytolysis processes and a change in the integrity and functional activity of the liver cell in individuals, an imbalance in the oxidant-antioxidant system, one of the reasons of which was the adverse occupational exposure to hazardous chemicals. An increase in catalase activity is a protective compensatory reaction during the activation of free radical oxidation processes.

scholarly journals Genome-Wide Mapping of Histone H3 Lysine 4 Trimethylation (H3K4me3) and Its Involvement in Fatty Acid Biosynthesis in Sunflower Developing Seeds

Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 706
Author(s):  
Antonio J. Moreno-Pérez ◽  
Raquel Martins-Noguerol ◽  
Cristina DeAndrés-Gil ◽  
Mónica Venegas-Calerón ◽  
Rosario Sánchez ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chromatin Remodeling ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Fatty Acid Biosynthesis ◽  
Acid Synthesis ◽  
Sunflower Seeds ◽  
Acid Biosynthesis ◽  
Functional Regions ◽  
Genome Wide

Histone modifications are of paramount importance during plant development. Investigating chromatin remodeling in developing oilseeds sheds light on the molecular mechanisms controlling fatty acid metabolism and facilitates the identification of new functional regions in oil crop genomes. The present study characterizes the epigenetic modifications H3K4me3 in relationship with the expression of fatty acid-related genes and transcription factors in developing sunflower seeds. Two master transcriptional regulators identified in this analysis, VIV1 (homologous to Arabidopsis ABI3) and FUS3, cooperate in the regulation of WRINKLED 1, a transcriptional factor regulating glycolysis, and fatty acid synthesis in developing oilseeds.

scholarly journals Unveiling the Dynamics of KRAS4b on Lipid Model Membranes

2021 ◽  
Author(s):  
Cesar A. López ◽  
Animesh Agarwal ◽  
Que N. Van ◽  
Andrew G. Stephen ◽  
S. Gnanakaran
Keyword(s):  
Molecular Mechanisms ◽  
Hypervariable Region ◽  
Small Gtpase ◽  
Model Systems ◽  
Coarse Grained ◽  
Regulatory Function ◽  
Limited Information ◽  
Long Time ◽  
Cell Growth And Differentiation ◽  
State Models

AbstractSmall GTPase proteins are ubiquitous and responsible for regulating several processes related to cell growth and differentiation. Mutations that stabilize their active state can lead to uncontrolled cell proliferation and cancer. Although these proteins are well characterized at the cellular scale, the molecular mechanisms governing their functions are still poorly understood. In addition, there is limited information about the regulatory function of the cell membrane which supports their activity. Thus, we have studied the dynamics and conformations of the farnesylated KRAS4b in various membrane model systems, ranging from binary fluid mixtures to heterogeneous raft mimics. Our approach combines long time-scale coarse-grained (CG) simulations and Markov state models to dissect the membrane-supported dynamics of KRAS4b. Our simulations reveal that protein dynamics is mainly modulated by the presence of anionic lipids and to some extent by the nucleotide state (activation) of the protein. In addition, our results suggest that both the farnesyl and the polybasic hypervariable region (HVR) are responsible for its preferential partitioning within the liquid-disordered (Ld) domains in membranes, potentially enhancing the formation of membrane-driven signaling platforms. Graphic Abstract

scholarly journals PSX-3 Antioxidant system characteristics in Saanen goats depending on performance

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 461-462
Author(s):  
Polina D Bokhan ◽  
Alesya A Bakhta ◽  
Larisa Y Karpenko ◽  
Anna I Kozitcyna ◽  
Anna B Balykina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Milk Yield ◽  
Antioxidant System ◽  
Free Radical Oxidation ◽  
Dairy Goat ◽  
Blood Levels ◽  
Lactation Performance ◽  
Radical Oxidation ◽  
System Characteristics

Abstract Dairy goat breeding is widespread worldwide. Goat milk and other derivative products are an important part of nutrition. Dairy products are the most important part of goat breeding; therefore, lactation performance is a relevant issue. The purpose of this study was to evaluate antioxidant system characteristics in Saanen goats depending on lactation performance. The experiment was conducted in the north-western region of Russian Federation, in the laboratories of the biochemistry and physiology departments at FSBEI of Higher Education «SPbSAVM». The three experimental groups included 30 Saanen goats each, 2nd–3rd lactations, selected using matched pairs method. 1st group included low milk producing ability goats (< 600 kg of milk yield per year), 2nd group included average milk producing ability goats (600–800 kg of milk yield per year), 3rd group included high milk producing ability goats (>800 kg of milk yield per year). The blood samples were taken once: at peak lactation performance (45 days after parturition). The blood levels of lipid peroxygenation markers (malondialdehyde, dienketone and conjugated dienes) and superoxide dismutase and catalase activity were assessed by standard methods. Results presented as mean±standard error of the mean. Student’s t-test was used after proving normal distribution. Level of significance is labeled as P < 0.05. The results are displayed in table 1 and 2. After analyzing the received data of antioxidant system characteristics, we found a high intensity of free-radical oxidation in high milk producing ability goats. This results in oxidative stress development. Activity of anti-oxidizing enzymes was elevated; therefore, free-radical oxidation is intensive. Consequently, these data allow us to take into consideration exogenous anti-oxidizing agents administration in high milk producing ability goats in order to reduce oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document