scholarly journals Pathogenetic Justification for the Use of Folates for the Prevention of Congenital Malformations

2017 ◽  
Vol 23 (2) ◽  
Author(s):  
V Mischenko ◽  
I Rudenko ◽  
M Holubenko ◽  
A Lavrinenko ◽  
K Tumasian
Keyword(s):  
Congenital Malformations ◽  
Methylenetetrahydrofolate Reductase ◽  
Reproductive Age ◽  
Detoxification Enzymes ◽  
Second Phase ◽  
Glutathione S Transferase ◽  
Hereditary Predisposition ◽  
Detoxification System ◽  
Folate Cycle ◽  
Homocysteine Methyltransferase

The frequency and severity of congenital malformations (CMF) do not tend to decline in modern society. CMF for etiologic factors are referred to the pathologies of a multifactorial nature. Among the many causative factors of CMF there is a hereditary predisposition.         The objective of the study was to increase the effectiveness of complex individualized prophylaxis of congenital malformations in women with polymorphic alleles of genes of folate cycle enzymes, the second phase of the detoxification system through the use of diagnostic, preventive, and therapeutic measures.         Materials and methods. 120 women of reproductive age who live in the city of Odessa and the Odessa region were examined. The alleles of the genes of the folate cycle enzymes of methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate homocysteine methyltransferase reductase (MTRR), glutathione-S-transferase M1 (GSTM1), folate acid, cyanocobalamin were determined.         Results of the study and their discussion. The determination of the polymorphic alleles of the genes of the folate cycle enzymes of methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate homocysteine methyltransferase reductase (MTRR), glutathione-S-transferase M1 (GSTM1), low folate, cyanocobalamin indicates the presence of a hereditary predisposition to the emergence of CMF, before and during pregnancy. Polymorphism of genes that control the synthesis of GSTM1 may alter the activity of detoxification enzymes. Expression of genes of GSTM1 enzymes begins in the embryonic period. Glutathione-dependent detoxification plays a key role in disinfecting of DNA peroxides. Mistakes of metabolism, functions of the corresponding enzymes are realized by chromosomal abnormalities and the risk of the occurrence of CMF, which requires the use of antioxidant therapy before and during pregnancy.         Conclusions. It was found that a high (about 55%) frequency of the polymorphic alleles of the genes of folate cycle enzymes MTHFR (homozygous – 10.0%, heterozygous – 16.7%), 5 MTRR (homozygous 12.5%, heterozygous – 15.5%) , the second phase of the GSTM1 detoxification system (homozygous – 13.3%, heterozygous – 15.8%), the content below the reference values of folic acid in 26.7%, cyanocobalamin – in 63.4% of observations indicates a hereditary predisposition and may contribute the emergence of CMF, which explains the expediency of timely use of preventive measures including folates, antioxidants.

scholarly journals THE RELATIONSHIP BETWEEN THE FREQUENCY OF CONGENITAL MALFORMATIONS IN NEWBORNS OF WOMEN RESIDING IN AN INDUSTRIAL REGION WITH THE POLYMORPHISM OF THE GENES OF THE BIOTRANSFORMATION SYSTEM

2018 ◽  
Vol 97 (7) ◽  
pp. 585-590
Author(s):  
Olga N. Gulyaeva ◽  
A. S. Kazitskaya ◽  
M. V. Alekseeva ◽  
L. V. Renge ◽  
A. G. Zhukova
Keyword(s):  
High Risk ◽  
Congenital Malformations ◽  
Mutagenic Activity ◽  
Reproductive Age ◽  
Glutathione S Transferase ◽  
Industrial Region ◽  
Fetal Malformations ◽  
Xenobiotic Biotransformation ◽  
The Relationship ◽  
Biotransformation System

Introduction. There is a number of polymorphic genes, the products of which take part in the biotransformation process and possess of the different activity. As a result of an imbalance in the processes of xenobiotic biotransformation, there is occurred an accumulation of toxic electrophilic compounds, the rise in a mutagenic activity, that can be very important in the formation of congenital malformations. Therefore, the study of the association of gene polymorphisms of the first and second phases of biotransformation with various congenital malformations is topical. The aim of the study. To investigate the role of the polymorphism of genes of the xenobiotic biotransformation system (CYP1A2*1F, GSTT1, GSTM1) encoding the enzymes I and II detoxification phases in women with the complicated obstetric history, residing in an industrial region. Material and methods. A survey of 53 women of reproductive age living in the territory of Novokuznetsk was carried out. The comparison group (the control) consisted of 27 women. These women did not have spontaneous miscarriages, and they carried the fetus to term without congenital malformations. The study group included 26 women who gave birth to babies with congenital malformations. Genomic DNA was isolated by the phenol-chloroform extraction method followed by the ethanol precipitation. The molecular and genetic analysis of the gene polymorphism of cytochrome 1A2 (CYP1A2), glutathione S-transferase τ-1 (GSTT1) and glutathione S-transferase μ-1 (GSTM1) was carried out using Real-Time mode. Results. A high risk of congenital fetal malformations in women with the A/A CYP1A2*1F genotype and resistance to these pathologies in the presence of a heterozygous form of the gene C/A CYP1A2*1F was revealed. The relationship between the high risk of stillbirth due to the placental insufficiency in women with deletion polymorphism of the gene GSTM1 “-”, while the normal functioning gene GSTM1 “+” was associated with the resistance to antenatal fetal death.

Role of the Renin-Angiotensin-Aldosterone System and the Glutathione S-Transferase Mu, Pi and Theta Gene Polymorphisms in Cardiotoxicity after Anthracycline Chemotherapy for Breast Carcinoma

2013 ◽  
Vol 28 (4) ◽  
pp. 336-347 ◽  
Author(s):  
Daniela Vivenza ◽  
Mauro Feola ◽  
Ornella Garrone ◽  
Martino Monteverde ◽  
Marco Merlano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Polymorphisms ◽  
Left Ventricular ◽  
Detoxification Enzymes ◽  
Left Ventricular Ejection ◽  
Glutathione S Transferase ◽  
Renin Angiotensin Aldosterone System ◽  
Ventricular Ejection Fraction ◽  
Renin Angiotensin ◽  
Anthracycline Chemotherapy

Background Anthracyclines are among the most active drugs against breast cancer, but can exert cardiotoxic effects eventually resulting in congestive heart failure (CHF). Identifying breast cancer patients at high risk of developing cardiotoxicity after anthracycline therapy would be of value in guiding the use of these agents. Aims We determined whether polymorphisms in the renin-angiotensin-aldosterone system (RAAS) and in the glutathione S-transferase (GST) family of phase II detoxification enzymes might be useful predictors of left ventricular ejection fraction (LVEF) kinetics and risk of developing CHF. We sought correlations between the development of cardiotoxicity and gene polymorphisms in 48 patients with early breast cancer treated with adjuvant anthracycline chemotherapy. Methods We analyzed the following polymorphisms: p.Met235Thr and p.Thr174Met in angiotensinogen ( AGT), Ins/Del in angiotensin-converting enzyme ( ACE), A1166C in angiotensin II type-1 receptor ( AGTR1A), c.-344T>C in aldosterone synthase ( CYP11B2), p.Ile105Val in GSTP1. Additionally, we analyzed the presence or absence of the GSTT1 and GSTP1 genes. A LVEF <50% was detected at least once during the 3 years of follow-up period in 13 out of 48 patients (27.1%). Conclusion RAAS gene polymorphisms were not significantly associated with the development of cardiotoxicity. GSTM1 may be useful as a biomarker of higher risk of cardiotoxicity, as demonstrated in our cohort of patients (p=0.147).

Transcriptome analysis of Tetranychus cinnabarinus responses to an insecticide exposure

2020 ◽  
Vol 25 (7) ◽  
pp. 1329-1342
Author(s):  
Jia Chen ◽  
Xianyan Ye ◽  
Jing Wang ◽  
Bin Xia ◽  
Tianrong Xin
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Degradation Pathway ◽  
Differentially Expressed ◽  
Detoxification Enzymes ◽  
Tetranychus Cinnabarinus ◽  
Glutathione S Transferase ◽  
Chitin Synthesis ◽  
Sublethal Concentrations ◽  
Synthesis And Degradation

Diflubenzuron, a benzoylphenylurea insecticide that interferes with chitin biosynthesis, causes arthropods to moult abnormally and die. However, its mechanism of action in Tetranychus cinnabarinus is still unclear. In order to explore the effects of different sublethal concentrations of diflubenzuron on T. cinnabarinus, we conducted a high-throughput RNA-seq technology to identify the variations in transcriptomic profile of T. cinnabarinus larvae. The results revealed that 470 and 49 differentially expressed genes were identified in LC50-and LC70-treated groups, comparing with the control. We also identified and analyzed the detoxification enzymes involved in the transcritome of T. cinnabarinus, including 34 cytochrome P450 genes, 17 glutathione-s-transferase genes (GSTs), 12 acetylcholinesterase genes (AChEs) and 9 ABC transporter genes. In addition, differentially expressed genes analysis showed that the gene expression levels of detoxification enzymes were generally enhanced. At the same time, seven and eleven genes were involved in chitin synthesis and degradation ways, respectively. The expression level of most genes involved in chitin synthesis and degradation pathway were generally up-regulated after exposure to sublethal concentrations of diflubenzuron. Moreover, for transcriptome validation, the mRNA expression results of ten specially expressed genes by quantitative real-time PCR demonstrated that these gene expression trends were consistent with that of the transcriptome data. Together, all these results suggested that sublethal concentrations of diflubenzuron exposure affected gene expression of major detoxification enzymes and chitin metabolism genes in T. cinnabarinus larvae. These findings may be helpful to further understand the possible molecular mechanism of benzoylphenylurea insecticides in T. cinnabarinus, as well as in other spider mites.

scholarly journals Risk and Toxicity Assessment of a Potential Natural Insecticide, Methyl Benzoate, in Honey Bees (Apis mellifera L.)

Insects ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 382
Author(s):  
Yu-Cheng Zhu ◽  
Yanhua Wang ◽  
Maribel Portilla ◽  
Katherine Parys ◽  
Wenhong Li
Keyword(s):  
Honey Bees ◽  
Insect Pests ◽  
Toxicity Assessment ◽  
Adverse Impact ◽  
Methyl Benzoate ◽  
Detoxification Enzymes ◽  
Glutathione S Transferase ◽  
Oral Toxicity ◽  
Proper Formulation ◽  
Potential Alternative

Methyl benzoate (MB) is a component of bee semiochemicals. Recent discovery of insecticidal activity of MB against insect pests provides a potential alternative to chemical insecticides. The aim of this study was to examine any potential adverse impact of MB on honey bees. By using two different methods, a spray for contact and feeding for oral toxicity, LC50s were 236.61 and 824.99 g a.i./L, respectively. The spray toxicity was 2002-fold and 173,163-fold lower than that of imidacloprid and abamectin. Piperonyl butoxide (PBO, inhibiting P450 oxidases [P450]) significantly synergized MB toxicity in honey bees, indicating P450s are the major MB-detoxification enzymes for bees. Assessing additive/synergistic interactions indicated that MB synergistically or additively aggravated the toxicity of all four insecticides (representing four different classes) in honey bees. Another adverse effect of MB in honey bees was the significant decrease of orientation and flight ability by approximately 53%. Other influences of MB included minor decrease of sucrose consumption, minor increase of P450 enzymatic activity, and little to no effect on esterase and glutathione S-transferase (GST) activities. By providing data from multiple experiments, we have substantially better understanding how important the P450s are in detoxifying MB in honey bees. MB could adversely affect feeding and flight in honey bees, and may interact with many conventional insecticides to aggravate toxicity to bees. However, MB is a relatively safe chemical to bees. Proper formulation and optimizing proportion of MB in mixtures may be achievable to enhance efficacy against pests and minimize adverse impact of MB on honey bees.

Both the folate cycle and betaine‐homocysteine methyltransferase contribute methyl groups for DNA methylation in mouse blastocysts

2014 ◽  
Vol 29 (3) ◽  
pp. 1069-1079 ◽  
Author(s):  
Baohua Zhang ◽  
Michelle M. Denomme ◽  
Carlee R. White ◽  
Kit‐Yi Leung ◽  
Martin B. Lee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methyl Groups ◽  
Betaine Homocysteine Methyltransferase ◽  
Folate Cycle ◽  
Homocysteine Methyltransferase

scholarly journals ROLE OF GENETIC PREDISPOSITION, GENE POLYMORPHISM OF GLUTATHIONE-S-TRANSFERASE (GSTT1, GSTM1, GSTP1) AND SOME ADVERSE FACTORS IN DEVELOPMENT OF BRONCHIAL ASTHMA IN CHILDREN – RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS

2021 ◽  
Vol 26 ◽  
pp. 449-463
Author(s):  
Ye. Stepanova ◽  
◽  
I. Kolpakov ◽  
V. Vdovenko ◽  
V. Zigalo ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Bronchial Asthma ◽  
Gene Deletion ◽  
Molecular Genetic ◽  
Glutathione S Transferase ◽  
Genetic Studies ◽  
Hereditary Predisposition ◽  
Gstm1 Gene ◽  
Polymorphic Variants ◽  
Asthma In Children

Objective: to determine the influence of hereditary predisposition, polymorphism of GSTT1, GSTM1, GSTP1 genes and environmental factors on the development of bronchial asthma in children – residents of radioactively contaminated areas. Materials and methods. School-age children-residents of radioactively contaminated areas with bronchial asthma, and those without clinical signs of respiratory pathology were examined. Genetic, medical, biological and social risk factors were determined based on the study of anamnestic data and medical records. Ventilation lung capacity was assessed by the method of computer spirometry. Molecular genetic studies were carried out using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. Results. Molecular genetic studies of the distribution of genotypes and frequencies of polymorphic variants of the genes GSTT1, GSTM1, GSTP1 were performed in children living under long-term intake of 137Cs by food chains. It was found that in children with BA the tendency to frequency of the deletion variant of the GSTT1 and GSTM1 genes in comparison with children without bronchial and pulmonary pathology was increased. The study of distributing the GSTP1 A313G gene polymorphic variants revealed in children with BA a significant increase in the frequency of AG-genotype, compared with the data of reference group. Adverse factors that increase the risk of developing bronchoobstructive disorders and the probability of their implementation in the form of bronchial asthma in children residents of RCA have been identified. It is established that among them the leading role is played by hereditary predisposition to this disease. On the part of the child, such negative factors were unfavorable conditions of fetal development, the presence of signs of exudative-catarrhal diathesis, manifestations of allergies and frequent respiratory diseases from the first months of life. It was found that the risk of developing BA was significantly increased in children with the GSTT1 and GSTM1 gene deletion genotypes; an increased risk of developing BA in children with a combination of the GSTP1 A313G gene polymorphism with deletion polymorphism of the GSTT1 or GSTM1 gene was determined. Сonclusion. Оne of the leading mechanisms, due to which there is a realization of hereditary predisposition to bronchial asthma in children living under constant intake of radionuclides with a long half-life, is the polymorphism of certain glutathione-S-transferase genes, namely, GSTT1, GSTM1 and A313G gene deletion polymorphism and GSTP1 gene polymorphism. Key words: children, radioactively contaminated areas, risk factors, bronchial asthma, glutathione-S-transferase gene polymorphism.

scholarly journals Effectiveness of preconceptional prevention of gestational complications by using folates

2018 ◽  
Vol 22 (1) ◽  
pp. 194-197
Author(s):  
V.P. Mishchenko ◽  
I.V. Rudenko ◽  
M.Yu. Golubenko ◽  
N.A. Stamova
Keyword(s):  
Congenital Malformations ◽  
Metabolic Disorders ◽  
The Body ◽  
Initial State ◽  
Reduction Processes ◽  
Drug Of Choice ◽  
Perinatal Pathology ◽  
Oxidation Reduction ◽  
Modern Drug ◽  
Folate Cycle

Preconceptional prophylaxis is a component of medicine, prevents occurrence of gestational complications, perinatal pathology, including congenital malformations. 30 patients and their husbands were examined who underwent preconception training 3 months prior to fertilization and 30 women without preconception training were examined. Preventing gestational complications, perinatal pathology, including congenital malformations, is advisable to begin at least 3 to 4 months before fertilization. This makes it possible to evaluate the premorbid background of the organisms of future parents, to determine and conduct a pathogenetically substantiated differentiated individualized complex stage full-fledged correction of metabolic disorders, taking into account the possible hereditary disruption of the activity of specific enzymes. The effectiveness of preconception prophylaxis of gestational complications depends both on the timely evaluation of the initial state of the organism of future parents and on the correction of the vitamin content in the body, which contributes to the stabilization of oxidation-reduction processes, folate cycle, balanced exchange of macro- and microelements under the control of the initial and the dynamics of monitoring the levels of these substances. The most modern drug of choice for the correction of the content of vitamins, macro-, microelements, amino acids is the vitamin complex Natalker I-II.

scholarly journals Breast cancer prevention in districts affected by the Chernobyl nuclear power plant accident beginning from child ages

2021 ◽  
pp. 29-35
Author(s):  
Yu.I. Bandazhevskyi ◽  
◽  
N.F. Dubovaya ◽  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Genetic Predisposition ◽  
Nuclear Power ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
The Body ◽  
Exclusion Zone ◽  
Folate Cycle

The aim of this paper was to assess the prevalence of the T risk allele of the MTHFR:677 genetic polymorphism in a group of girls from Ivankovsky and Polessky districts located near the Chernobyl exclusion zone. In addition, we assessed variants of combined carriership of the T allele with risk alleles of other genetic polymorphisms regulating the folate cycle. Research methods. Immunochemical, statistical. Results. Genetic predisposition to breast cancer risk was analyzed in a group of 251 adolescent girls. Carriership of the T allele of the MTHFR:С677Т polymorphism was found in 142 children (56.6%), while the homozygous T/T variant was found in 25 girls, or in 10.0% of cases. Compound heterozygosity for the 677CT/1298AC alleles of the MTHFR gene was recorded in 60 individuals, or in 23.9% of cases. Conclusions. The revealed genetic changes in the folate cycle lead to a significant decrease in the activity of methylenetetrahydrofolate reductase, and, accordingly, to an increase in the level of homocysteine in the blood, creating conditions for the occurrence of breast cancer. Given the high level of genetic predisposition, taking into account the constant impact on the body of radioactive elements and their decay products, the occurrence, as a consequence, of serious metabolic disorders, it is necessary to identify the breast cancer risk group of children.

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