Functioning Of Antioxidant System Research Articles

Intracellular Iron Deficiency and Abnormal Metabolism, Not Ferroptosis, Contributes to Homocysteine-Induced Vascular Endothelial Cell Death.

Background/Objectives: Homocysteine (Hcy) and iron are factors co-related with the progression of cardiovascular diseases. The vascular endothelium is an important barrier for physiological homeostasis, and its impairment initiates cardiovascular injury. However, the mechanism underlying Hcy-caused vascular endothelial cell injury and the participation of iron are not fully elucidated. This study aims to investigate the Hcy-induced vascular endothelial injury and iron metabolism dysfunction as well as the underlying molecular mechanism. Methods: Human umbilical vein endothelial cells (HUVECs) were employed as the experimental model to examine the Hcy-induced endothelial injury and its underlying mechanism via various biochemical assays. Results: Hcy suppressed the cell viability and proliferation and caused cell death in a concentration-dependent manner. Hcy induced cell cycle arrest, apoptosis, and autophagy as well as impairment of intracellular energy metabolism. Hcy disrupted the intracellular antioxidant system and mitochondrial function by increasing intracellular ROS, MDA and mitochondrial content, and decreasing the SOD activity and mitochondrial membrane potential. Hcy significantly reduced the GSH-Px activity along with the accumulation of intracellular GSH in a concentration-dependent manner. Ferroptosis inhibitors, Ferrostatin-1 (Fer-1), and Deferoxamine (DFO) significantly decreased the Hcy-caused cytotoxicity accompanied by a reduction in dysregulated mitochondria content, but only DFO ameliorated the elevation of intracellular ROS, and neither Fer-1 nor DFO affected the Hcy-caused reduction in intracellular ATP. In addition, Hcy decreased the intracellular concentration of iron, and supplementing Hcy with various concentrations of Fe3+ increased the cell viability and decreased the LDH release in a concentration-dependent manner. Hcy dramatically decreased the mRNA expression level of transferrin receptor while increasing the mRNA expression levels of transferrin, ferritin light chain, ferritin heavy chain, ferroportin, and SLC7A11. Moreover, Hcy suppressed the protein expression of phospho-Akt, phospho-mTOR, Beclin-1, LC3A/B, Nrf2, HO-1, phospho-MEK1/2, phospho-ERK1/2, and Caspase-3 in concentration- and time-dependent manners. Conclusions: Hcy-induced vascular endothelial injury is likely to be associated with apoptosis and autophagy, but not ferroptosis. The key underlying mechanisms are involved in the disruption of the intracellular antioxidant system and iron metabolism via regulation of PI3K/Akt/mTOR, MAPKs, Nrf2/HO-1, and iron metabolism.

Differences in the Effect of Beta-Hydroxybutyrate on the Mitochondrial Biogenesis, Oxidative Stress and Inflammation Markers in Tissues from Young and Old Rats.

One of the therapeutic approaches to age-related diseases is modulation of body cell metabolism through certain diets or their pharmacological mimetics. The ketogenic diet significantly affects cell energy metabolism and functioning of mitochondria, which has been actively studied in various age-related pathologies. Here, we investigated the effect of the ketogenic diet mimetic beta-hydroxybutyrate (BHB) on the expression of genes regulating mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam), quality control (Sqstm1), functioning of the antioxidant system (Nfe2l2, Gpx1, Gpx3, Srxn1, Txnrd2, Slc6a9, Slc7a11), and inflammatory response (Il1b, Tnf, Ptgs2, Gfap) in the brain, lungs, heart, liver, kidneys, and muscles of young and old rats. We also analyzed mitochondrial DNA (mtDNA) copy number, accumulation of mtDNA damage, and levels of oxidative stress based on the concentration of reduced glutathione and thiobarbituric acid-reactive substances (TBARS). In some organs, aging disrupted mitochondrial biogenesis and functioning of cell antioxidant system, which was accompanied by the increased oxidative stress and inflammation. Administration of BHB for 2 weeks had different effects on the organs of young and old rats. In particular, BHB upregulated expression of genes coding for proteins associated with the mitochondrial biogenesis and antioxidant system, especially in the liver and muscles of young (but not old) rats. At the same time, BHB contributed to the reduction of TBARS in the kidneys of old rats. Therefore, our study has shown that administration of ketone bodies significantly affected gene expression in organs, especially in young rats, by promoting mitochondrial biogenesis, improving the functioning of the antioxidant defense system, and partially reducing the level of oxidative stress. However, these changes were much less pronounced in old animals.

Glutathione is required for nitric oxide-induced chilling tolerance by synergistically regulating antioxidant system, polyamine synthesis, and mitochondrial function in cucumber (Cucumis sativus L.)

In this paper, we discussed the physiological mechanism of enhanced chilling tolerance with combined treatment of nitric oxide (NO) and reduced glutathione (GSH) in cucumber seedlings. With prolonged low temperature (10 °C/6 °C), oxidative stress improved, which was manifested as an increase the hydrogen peroxide (H2O2) and malondialdehyde (MDA), causing cell membrane damage, particularly after 48 h of chilling stress. Exogenous sodium nitroprusside (SNP, NO donor) enhanced the activity of nitric oxide synthase NOS-like, the contents of GSH and polyamines (PAs), and the cellular redox state, thus regulating the activities of mitochondrial oxidative phosphorylation components (CI, CII, CIV, CV). However, buthionine sulfoximine (BSO, a GSH synthase inhibitor) treatment drastically reversed or attenuated the effects of NO. Importantly, the combination of SNP and GSH treatment had the best effect in alleviating chilling-induced oxidative stress by upregulating the activities of antioxidant enzyme, including superoxidase dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD) and improved the PAs content, thereby increased activities of CI, CII, CIII, CIV, and CV. This potentially contributes to the maintenance of oxidative phosphorylation originating from mitochondria. In addition, the high activity of S-nitrosoglutathione reductase (GSNOR) in the combined treatment of SNP and GSH possibly mediates the conversion of NO and GSH to S-nitrosoglutathione. Our study revealed that the combined treatment with NO and GSH to synergistically improve the cold tolerance of cucumber seedlings under prolonged low-temperature stress.

From Epimedium to Neuroprotection: Exploring the Potential of Wushanicaritin.

Epimedium has been used for functional foods with many beneficial functions to human health. Wushanicaritin is one of the most important chemicals int Epimedium. This study investigated the neuroprotective effects of wushanicaritin and potential underlying mechanisms. The results demonstrated that wushanicaritin possessed superior intercellular antioxidant activity compared to icaritin. Wushanicaritin, with an EC50 value of 3.87 μM, showed better neuroprotective effect than quercetin, a promising neuroprotection agent. Wushanicaritin significantly reversed lactate dehydrogenase release, reactive oxygen species generation, cell apoptosis, and mRNA expression related to cell apoptosis and oxidative defense, in glutamate-induced PC-12 cells. Wushanicaritin could also maintain the enzymatic antioxidant defense system and mitochondrial function. The suppression of caspase-3 activation and amelioration of mitochondrial membrane potential loss and nucleus morphology changes were involved in the antiapoptotic effect of wushanicaritin. These findings suggested that wushanicaritin possesses excellent intercellular antioxidant and neuroprotective activities, showing potential promise in functional foods.

Protective Effect of Prunetin on Isoproterenol-Induced Myocardial Infarction in Wistar Rats via Biochemical Characterization.

The development of MI following ischemia damage is influenced by oxidative stress. Myocardial Infarction (MI) generates myocardial ischemia injury, which damages the cardiomyocytes. Ischemia builds up to a critical level over time in MI, causing permanent myocardial cell damage or death. The current study sought to determine whether Prunetin (PRU) could protect against Isoproterenol (ISO)-induced cardiac heart failure in rats by examining cardiac diagnostic markers, lipid peroxidation products, enzymatic and non-enzymatic antioxidant levels, and histological changes. PRU (20 mg/kg bwt) was orally administered for 19 days to rats, and after the treatment, ISO (85 mg/kg bwt) was subcutaneously administered with an intermission of 24 h for a couple of days to induce myocardial infarction on 20th and 21st days. ISO-treated rats exhibited considerable alterations in cardiac-sensitive markers in the serum. The levels of lipid peroxidation markers augmented drastically in the plasma and myocardium. Enzymatic antioxidant levels in erythrocytes and myocardium and the states of non-enzymatic antioxidants were diminished in the plasma and heart tissue of ISO-treated rats. The histopathological examination of heart tissue exhibited cardiac damage in ISO-induced rats. The oral administration of PRU significantly lowered the levels of lipid peroxidation and biochemical indicators, while significantly improving the antioxidant system function of ISO-interposed rats. In PRU-treated ISO-injected rats, histological examinations revealed suppressed myocardial destruction. Our research shows that oral pretreatment of PRU prevented ISO-induced oxidative stress in MI.

Impact of glyphosate-based herbicide exposure through maternal milk on offspring's antioxidant status, neurodevelopment, and behavior.

Glyphosate-based Herbicide (GBH) is a widely used pesticide that functions as a broad-spectrum, non-selective herbicide. Despite advanced research to describe the neurotoxic potential of GBH, the harmful effects on maternal behavior and neurodevelopment of offspring remain unclear. This study was conducted to highlight the effects of GBH on the antioxidant system, anxiety traits, social interaction, and cognitive and sensorimotor functions in pups exposed to 25 or 50mg/l daily via their mother's milk. Concerning the biochemical biomarkers, GBH administered during the early stages of development negatively affected the status of antioxidant enzymes and lipid peroxidation in the brain structures of the pups. Furthermore, our results showed a significant decrease in acetylcholinesterase (AChE) specific activity within the brains of treated pups. The results of the behavioral tests indicated that the treated offspring developed anxiety, memory, and sociability disorders, as evidenced by the Open Field, Y-maze, object recognition task, and social interaction tests. Through neurodevelopmental testing, we also showed sensorimotor impairment (righting reflex and negative geotaxis) and abnormal maternal behavior. Altogether, our study clearly demonstrates that the developing brain is sensitive to GBH.

Cell and animal models of age‐related macular degeneration: Focus on oxidative stress and protein aggregation

Age‐related macular degeneration (AMD) is a multifactorial disease with a long asymptomatic development period. Due to its multifactorial feature and slow development, disease modelling capturing all the elements becomes difficult if not impossible. The disease has a strong genetic background in form of certain polymorphisms in the complement system and ARMS2/HTRA1 genes providing tools for studies regarding genetics. However, AMD is much more than genetics. At least prolonged oxidative stress and subsequent protein accumulation and aggregation together with local inflammation developing to chronic in retinal pigment epithelial (RPE) cells are the key elements of the cellular pathogenesis of AMD. The RPE cells are quiescent and responsible for the wellbeing of the entire retina functioning as the link between choroidal vasculature and other layers of the retina providing necessary support for normal retinal functions. Therefore, disturbance on the cellular homeostasis of the RPE compromise the function of the entire retina. Despite being such an integral part of the retina responsible for the vision, the RPE cells withstand one the highest levels of oxidative stress throughout a lifetime of an individual. This sets certain demands for the antioxidant system's capacity to eliminate harmful oxidant molecules and prevent the spread of oxidative injury inside the cell leading to oxidative stress. However, constant oxidative challenge leads to damages on the protective system and becomes more deleterious over time. Proteins are especially prone to oxidative damage resulting increased levels of dysfunctional or aggregating proteins challenging the repair/degradative systems of the cell. Modification of oxidative status or protein degradation systems have been shown to simulate the disease state in the RPE cells and leading to a disease resembling phenotype. In vitro models are efficient tools studying certain cell specific molecular pathways such as oxidative stress, function of antioxidant defence system, and repair/degradative pathways and discovering potential druggable targets. In vivo animal models offer information how these pathways function in a native environment and how the in vitro results are translated to a functional living organism. Also, animal models offer information about the potential administration routes as well as important pharmacological data, for example. The use of most common animals in research, rodents, needs genetic engineering, for example, to achieve desired disease modelling phenotype often lacking some critical features of the disease. However, the use of these models has greatly increased the understanding of AMD pathogenesis, lead to new discoveries on disease development later confirmed in patient population, and offered new treatment strategies.

Gender Differences of Antioxidant System and Thyroid Function in Depressed Adolescents with Non-Suicidal Self-Injury.

The aim of our study was to explore the relation between serum levels of non-enzymatic antioxidants, thyroid function with the risk of non-suicidal self-injury (NSSI) in depressed adolescents. We retrospected the electronic records of 454 hospitalized patients aged 13-17 years old with a diagnosis of major depressive disorder (239 patients with NSSI and 215 subjects without NSSI), and collected their demographic and clinical information, including serum levels of total bilirubin (Tbil), uric acid (UA), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH). The incidence of NSSI was 52.6% among depressed adolescents aged 13-17, 57.1% in female and 38.5% in male. After using the propensity scoring method to exclude the influence of age between the two groups, it was found that patients with NSSI showed lower levels of Tbil (P=0.046) and UA (P=0.015) compared with those without NSSI. Logistic regression results showed that serum UA was associated with NSSI behavior in female patients (OR=0.995, 95% CI: 0.991-0.999, P=0.014), and TSH was associated with NSSI in male participants (OR=0.499, 95% CI: 0.267-0.932, P=0.029). Female and male may have different pathological mechanisms of NSSI. NSSI is more likely to be related to antioxidant reaction in female adolescent patients, while more likely to be related to thyroid function in male depressed adolescent patients.

SkQ1 improves immune status and normalises the activity of antioxidant and nadph-generating enzymes in adjuvant-induced rheumatoid arthritis in rats

Rheumatoid arthritis (RA) is a severe systemic autoimmune inflammatory disease. Oxidative stress and excessive formation of mitochondrial reactive oxygen species (ROS) are now considered to be the central pathogenetic mechanisms of connective tissue component destruction and the factors responsible for a highly active inflammatory process and autoimmune response. The aim of the present work was to evaluate the effect of mitochondrial-directed antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on immune status, intensity of free radical-induced oxidation and functioning of antioxidant system (AOS) and NADPH-generating enzymes in rats with adjuvant-induced RA. Laboratory animals were divided into 4 groups: a control group; a group of animals with RA; animals injected intraperitoneally with SkQ1 at a dose of 1250 nmol/kg every 24 hours during the next 8 days from day 7 of RA development, and animals given SkQ1 at a dose of 625 nmol/kg according to the above scheme. Material for the study was taken on day 15 after the start of the experiment. The rate of erythrocyte sedimentation, the level of circulating immune complexes, and the concentration of immunoglobulins A, M and G were determined in rats by enzyme immunoassay. The intensity of free radical-induced oxidation was assessed by iron-induced biochemiluminescence, diene conjugate content and aconitate hydratase activity. Enzyme activity and metabolite content in animal tissues were analysed spectrophotometrically. The results of the work showed that the development of RA was associated with an increase in the indicators of immune response and intensity of free radical-induced oxidation. The development of an imbalance in AOS functioning and an increase in the activity of NADPH-generating enzymes was also observed. The administration of SkQ1 resulted in a dose-dependent change in the oxidative status indicators towards the control, which was accompanied by the normalization of the immune status parameters. It seems that the tested compound decreased the level of mitochondrial ROS, resulting in an inhibition of the inflammatory response. The consequence of these changes could be inhibition of free radical generation by immunocompetent cells and subsequent mitigation of the severity of oxidative stress in the tissues.

The influence of heat stress on the antioxidant protection glutathione link and the content of lipid peroxidation products in chicken liver

Heat stress is one of the main reactions of the body’s response to environmental factors, negatively affecting the welfare of various animal species. An increase in environmental temperature can cause stress, which, in turn, potentially has various negative consequences for animals including disruption of the antioxidant system functioning. Violating the antioxidant-prooxidant balance can lead to an increased free radicals formation in the body, which can damage cells and promote the development of various diseases. The article presents the study results of the artificially simulated heat stress effect on individual indicators of the antioxidant system and lipid peroxidation products in the chickens’ liver. The choice of these animals for this study is due to the fact that the poultry is particularly sensitive to the elevated environmental temperatures and, accordingly, to heat stress. This is caused by the biological peculiarities of birds, in particular, they lack sweat glands, and their body surface is mostly covered with feathers, which, together with the high density of keeping in the industrial poultry farming, often leads to the heat stress. The purpose of this work was to find out the presence or absence of changes in individual indicators of the antioxidant system glutathione link and the lipid peroxidation products content in chickens’ liver. The analysis of indicators such as lipid hydroperoxides (LOOH), TBA-active products, reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) will allow us to obtain information about the body’s antioxidant defense system state and the oxidative stress level under heat stress conditions. In this study we used 18 hens of the white Leghorn breed. The research was conducted in the vivarium of the Institute of Animal Biology of the National Academy of Sciences in two stages. During the first stage, chickens were kept at an air temperature of 20°С for 7 days. During the second stage, we created heat stress conditions by increasing the temperature to 35°С 6 hours a day, also for 7 days. It has been found that as the ambient temperature increased, the content of LOOH, GSH, and activity of GSH-Px in the liver of chickens increased (P<0.01), while, on the contrary, the content of TBA-active products and activity of GR decreased (P<0.01). The obtained data prove the heat stress effect on the antioxidant protection glutathione link in chicken liver. Research results can be of practical value for improving the bird keeping conditions in the industrial poultry farming, developing strategies for protection against stress, and improving the conditions to ensure the animals’ welfare and health.

Application of Se-Met to CdTe QDs significantly reduces toxicity by modulating redox balance and inhibiting apoptosis

Cadmium tellurium quantum dots (CdTe QDs) as one of the most widely used QDs have been reported the toxicity and biosafety in recent years, little work has been done to reduce their toxicity however. Based on the mechanisms of toxicity of CdTe QDs on liver target organs such as oxidative stress and apoptosis previously reported by other researchers, we investigated the mechanism of action of trace element selenium (Se) to mitigate the hepatotoxicity of CdTe QDs. The experimental results showed that Se-Met at 40–140 μg L−1 could enhance the function of intracellular antioxidant defense system and the molecular structure of related antioxidant enzymes by reduce the production of ROS by 45%, protecting the activity of antioxidants and up-regulating the expression of selenoproteins with antioxidant functions, Gpx1 increase 225% and Gpx4 upregulated 47%. In addition, Se-Met could alleviate CdTe QDs-induced apoptosis by regulating two apoptosis-inducing factors, as intracellular caspase 3/9 expression levels were reduced by 70% and 87%, decreased Ca2+ concentration, and increased mitochondrial membrane potential measurements. Overall, this study indicates that Se-Met has a significant protective effect on the hepatotoxicity of CdTe QDs. Se-Met can be applied to the preparation of CdTe QDs to inhibit its toxicity and break the application limitation.

6-Hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline Demonstrates Anti-Inflammatory Properties and Reduces Oxidative Stress in Acetaminophen-Induced Liver Injury in Rats.

We examined the effects of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of liver injury, oxidative status, and the extent of inflammatory and apoptotic processes in rats with acetaminophen-induced liver damage. The administration of acetaminophen caused the accumulation of 8-hydroxy-2-deoxyguanosine and 8-isoprostane in the liver and serum, as well as an increase in biochemiluminescence indicators. Oxidative stress resulted in the activation of pro-inflammatory cytokine and NF-κB factor mRNA synthesis and increased levels of immunoglobulin G, along with higher activities of caspase-3, caspase-8, and caspase-9. The administration of acetaminophen also resulted in the development of oxidative stress, leading to a decrease in the level of reduced glutathione and an imbalance in the function of antioxidant enzymes. This study discovered that 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline reduced oxidative stress by its antioxidant activity, hence reducing the level of pro-inflammatory cytokine and NF-κB mRNA, as well as decreasing the concentration of immunoglobulin G. These changes resulted in a reduction in the activity of caspase-8 and caspase-9, which are involved in the activation of ligand-induced and mitochondrial pathways of apoptosis and inhibited the effector caspase-3. In addition, 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline promoted the normalization of antioxidant system function in animals treated with acetaminophen. As a result, the compound being tested alleviated inflammation and apoptosis by decreasing oxidative stress, which led to improved liver marker indices and ameliorated histopathological alterations.

Chromium mediated damaging effects on growth, nitrogen metabolism and chlorophyll synthesis in tomato can be alleviated by foliar application of melatonin and jasmonic acid priming

Efficiency of methyl-jasmonate (5 µM Me-J) priming and the foliar application of melatonin (100 µM ML) in assuaging the deleterious effects of chromium (Cr) toxicity on growth, nitrogen metabolism, chlorophyll synthesis and photosynthesis in tomato were studied. Chromium toxicity reduced growth, chlorophyll synthesis and photosynthesis significantly, however Me-J and ML significantly enhanced the parameters. Decline in the intermediates of chlorophyll biosynthesis pathway i.e., glutamate 1-semialdehyde, δ-amino levulinic acid, Mg-prototoporphyrin IX, prototoporphyrin IX and protochlorophyllide due to Cr was alleviated to considerable levels due to Me-J and ML treatment. Toxicity of Cr was evident as increased production of superoxide and hydrogen peroxide, and activity of lipoxygenase and protease while as Me-J and ML treatment alleviated the oxidative damage by causing significant decline in these parameters. Priming with Me-J and foliar application of ML alleviated the Cr toxicity induced decline in the activities of nitrogen metabolising enzymes. Treatment of Me-J and ML up-regulated the antioxidant system functioning, increased the content of secondary metabolites and activity of phenylalanine ammonia lyase. Accumulation of osmolytes increased due to Me-J and ML under normal as well as Cr toxicity conditions. Treatment of Me-J and ML increased the γ-glutamyl kinase activity with significant reduction in proline oxidase.

Korean Red Ginseng Prevents the Deterioration of Lung and Brain Function in Chronic PM2.5-Exposed Mice by Regulating Systemic Inflammation.

This study was conducted to confirm the effects of Korean red ginseng on lung and brain dysfunction in a BALB/c mice model exposed to particulate matter (PM)2.5 for 12 weeks. Learning and cognitive abilities were assessed with Y-maze, passive avoidance, and Morris water maze tests. To evaluate the ameliorating effect of red ginseng extract (RGE), the antioxidant system and mitochondrial function were investigated. The administration of RGE protected lung and brain impairment by regulating the antioxidant system and mitochondrial functions damaged by PM2.5-induced toxicity. Moreover, RGE prevented pulmonary fibrosis by regulating the transforming growth factor beta 1 (TGF-β1) pathway. RGE attenuated PM2.5-induced pulmonary and cognitive dysfunction by regulating systemic inflammation and apoptosis via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/c-Jun N-terminal kinases (JNK) pathway. In conclusion, RGE might be a potential material that can regulate chronic PM2.5-induced lung and brain cognitive dysfunction.

MRNA level of antioxidant genes and activity of NADPH-generating enzymes in rotenone-induced parkinsonism in rats

Aim. To analyze the mRNA level of genes encoding antioxidant enzymes and the transcription factors Nrf2 and Foxo1 regulating their expression and the activity of glucose-6-phosphate dehydrogenase (G6PDH) and NADPdependent isocitrate dehydrogenase (NADP-IDH) and assess the correlation between these parameters, oxidative status, and motor coordination parameters in rats with rotenone-induced parkinsonism.Materials and methods. The study was performed on male Wistar rats aged 4–6 months and weighing 200–250 g. Parkinsonism was modeled by subcutaneous administration of rotenone for 10 days at a dose of 2.5 mg / kg. To confirm the development of the pathology, motor coordination tests and histological staining of the cerebral cortex and striatum with hematoxylin and eosin were used. The oxidative status was analyzed based on the levels of conjugated dienes, carbonyl amino acid residues in proteins, and α-tocopherol. The enzyme activity was studied spectrophotometrically by the formation of NADPH. Real-time PCR was used to analyze the level of gene mRNA.Results. During the study, an increase in serum and brain concentrations of conjugated dienes, carbonyl amino acid residues, and α-tocopherol was observed in the experimental group of rats compared to the controls. It could be associated with the redistribution of this compound between tissues during pathology development. The animals with experimental parkinsonism, in addition, were characterized by a decrease in the mRNA level of the Sod1, Gpx1, Gsr, Gsta2, Nfe2l2, and Foxo1 genes, as well as the activity of G6PDH and NADP-IDH. In the rats with experimental parkinsonism, a negative correlation of NADPH-IDH activity in the brain with serum α-tocopherol level and a positive correlation with Gpx1 and Foxo1 mRNA levels in the striatum were found. The level of oxidatively modified proteins in the brain of the animals with PD was negatively correlated with the concentration of Gsta2 mRNA in the striatum, while the specific activity of G6PDH in the serum was characterized by the positive relationship with grip strength.Conclusion. The data obtained indicate that the inhibition of transcription of the genes encoding antioxidant enzymes and regulatory factors Nrf2 and Foxo1 contributed significantly to the development of oxidative stress in PD. A decrease in the activity of G6PDH and NADP-IDH led to a decrease in the availability of NADPH, which is a limiting factor in the functioning of the glutathione antioxidant system. Obviously, the inhibition of G6PDH and NADP-IDH was also an important pathogenic factor in the progression of the pathology. Along with a decrease in the content of antioxidant gene mRNA in the brain tissues, the level of α-tocopherol increased in the rats with parkinsonism, which could be the result of an imbalance in the functioning of antioxidant system.

비만한 암 생존자에게서 고려할 기능의학적 접근

Obesity in cancer survivors has a complex problem and is influenced by many psychological, social, and biological factors. Management of these factors is important to prevent recurrent cancer, secondary cancer, and other cardiovascular disease complications while improving cancer survivors’ quality of life, such as fatigue and pain. Factors of functional medicine in obesity in cancer survivors include excessive fat accumulation, low-grade chronic inflammation, excessive estrogen in estrogen-related cancer, intestinal dysbiosis and changes in the intestinal environment, changes in cellular energy metabolism and antioxidant capacity, vital hormones, autonomic nervous system, and immune system imbalance, etc. We need to change the fundamental living environment and implement individual nutritional treatment with functional medicine approach for each patient, rather than simply satisfying the goal of weight loss for obesity in cancer survivors. In this review, the management of obese cancer survivors was discussed from four perspectives (inflammation by adipose tissue and related hormones, influence of gut microbiome, cell metabolism, antioxidant system, and immune function) based on the 7-core imbalance theories of functional medicine.

Droughts and Thermo-Priming Enhance Acclimation to Later Drought and Heat Stress in Maize Seedlings by Improving Leaf Physiological Activity

Early heat and drought priming may increase the plant’s ability to resist later drought and heat stress. However, it remains unclear whether combined heat and drought priming can enhance the acclimation of plants to later combined stress by improving physiological activities. In this study, maize seedlings were first pre-exposed twice to heat, drought, and a combination of stresses followed by recovery, and then subjected to six days of more severe stresses. A considerable reduction in photosynthetic pigment content, stomatal size, and photosynthesis was observed under heat and drought conditions, and the changes in the above indicators were amplified under combined stress conditions. Stress priming improves antioxidant defense and cellular osmoregulation, as indicated by improved superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione reductase (GR), and ascorbate peroxidase activities, as well as elevated soluble sugar (SS) and proline (Pro) contents. Lower superoxide anion and malondialdehyde contents and injury index in the primed seedlings demonstrated the mitigation of oxidative stress. ROC analysis revealed that SOD and POD had considerable reliability in determining that maize seedlings were experiencing heat stress (AUC = 0.941–0.971); GR and SS were capable of accurately monitoring drought stress that was being experienced by plants (AUC = 0.919–0.958); and SOD, GR, and Pro had more capability for detecting the combination of heat and drought stress (AUC = 0.907–0.958). Collectively, the primed seedlings exhibited better performance than the non-primed seedlings, exhibiting stronger stress acclimation supported by an effective antioxidant defense system and osmoregulatory function.

CORRECTION OF CHANGES IN LIPID METABOLISM AND REDOX SYSTEM IN PATIENTS WITH STEMI IN THE SETTING OF INSULIN RESISTANCE

Myocardial infarction (STEMI) remains one of the most important problems of modern Cardiology both in Ukraine and worldwide due to its recalcitrant indices of incidence, disability and mortality. The prevalence of metabolic syndrome (MS) and DM2 in Ukraine is quite high, accounting for 20-28% in the general population and over 50% in certain demographics. In persons with abdominal obesity, metabolic syndrome and DM2, there is a 30% total risk of developing MI in the next 8 years, and their mortality rate is double thatof persons without metabolic disorders. The unfavorable prognosis in such patients is attributed to insulin resistance as an additional risk factor for CAD progression and the development of ACS, which determines the need to develop methods for correction of these abnormal processes.
 The aim of the research: to explore the efficacy of correcting the disorders of lipid profile and prooxidant/antioxidant system balance in patients with STEMI in a setting of insulin resistance and high risk of reperfusion complications by using dapagliflozin, a SGLT2 inhibitor.
 The methods of the research. The basis of the work has been underlain by the analysis of a comprehensive assessment and surgical treatment (percutaneous coronary intervention) in 73 patients with STEMI in the setting of insulin resistance in MS and DM2. The parameters of lipid profile and the activity of the components in the prooxidant/antioxidant system were determined by spectrophotometric methods; the absorbancy was measured on a Biomat 5 spectrophotometer (United Kingdom).The diagnosis of ACS was verified according to ESC Guidelines in the presence of a typical anginal attack, ACS-specific ECG changes with time (reciprocal ST displacement) and the signs of necrosis-resorption syndrome.The diagnosis was subsequently confirmed by the results of urgent coronary angiography. The diagnosis of MS and type 2 DM was made according to the recommendations of the WHO Expert Committee (2013) and the updated ADA/EASD consensus (2018).
 Results. In order to improve lipid profile and redox system balance in pre- and postoperative period, the patients were prescribed dapagliflozin at the dose of 10 mg/day, which allowed compensation of hyperglycemia, reduction of insulin resistance and stabilizing the activity of prooxidant/antioxidant system, preventing post-PCI reperfusion complications and stabilizing the clinical condition of comorbid patients in the postoperative period owing to a 40.4% reduction in the incidence of rhythm and conductivity disorders, and a 55.3% reduction in manifestations of acute heart failure. There has been a substantial reduction in free radical oxidation in the setting of dapagliflozin treatment, as suggested by a 1.3-fold reduction (р<0.05) in active products of thiobarbituric acid in the serum and a simultaneous restoration of functioning of enzymatic antioxidant systems, a 1.5-fold reduction (p<0.05) in the degree of superoxide dismutase blockage with an increased activity of catalase and ceruloplasmin.
 Conclusions. The use of dapagliflozin in pre- and postoperative patients with STEMI in the setting of insulin resistance and high surgical risk contributes to improvement of lipid metabolism and a significant reduction in the activity of free radical oxidation with restoration of functioning of enzymatic antioxidant systems in the body, which allows for a significant reduction in the incidence of rhythm and conduction disorders and the manifestations of acute heart failure.

Untargeted metabonomic analysis of non-alcoholic fatty liver disease with iron overload in rats via UPLC/MS

Background/Aims In recent years, many metabolites specific to nonalcoholic fatty liver disease (NAFLD) have been identified thanks to the application of metabolomics techniques. This study aimed to investigate the candidate targets and potential molecular pathways involved in NAFLD in the presence of iron overload. Methods Male Sprague Dawley rats were fed with control or high-fat diet with or without excess iron. After 8, 16, 20 weeks of treatment, urine samples of rats were collected for metabolomics analysis using ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). Blood and liver samples were also collected. Results High-fat, high-iron diet resulted in increased triglyceride accumulation and increased oxidative damage. A total of 13 metabolites and four potential pathways were identified. Compared to the control group, the intensities of adenine, cAMP, hippuric acid, kynurenic acid, xanthurenic acid, uric acid, and citric acid were significantly lower (p < 0.05) and the concentration of other metabolites was significantly higher in the high-fat diet group. In the high-fat, high-iron group, the differences in the intensities of the above metabolites were amplified. Conclusion Our findings suggest that NAFLD rats have impaired antioxidant system and liver function, lipid disorders, abnormal energy, and glucose metabolism, and that iron overload may further exacerbate these disorders.

Growth responses of wheat seedlings of different varieties to heat-stress and their relation to the antioxidant system state and osmolytes accumulation

Background. In recent decades, Ukraine has been experiencing abnormally high temperatures and droughts in different seasons, including autumn. This creates stressful conditions for winter cereals, especially wheat, at the very beginning of ontogeny. A comprehensive study of the functioning of antioxidant and osmoprotective systems in the early stages of development for wheat varieties of different ecological and geographical origins has not been conducted yet. This study aimed to investigate the effect of heat stress on the growth of etiolated seedlings of seven varieties of winter wheat (Triticum aestivum L.) and the indicators characterizing the functioning of antioxidant and osmoprotective systems. Materials and Methods. Wheat grains of different varieties were germinated at 24 °C for three days in the dark. Subsequently, they were subjected to 4 h of heating at 45 °C in an air thermostat. Immediately after stress, the generation of superoxide anion radical (O2•‒) by seedlings, the content of hydrogen peroxide (H2O2), lipid peroxidation (LPO) products, catalase and guaiacol peroxidase activity, and also proline and soluble carbohydrates were analyzed. One day after heating, the relative inhibition of shoot and root growth was determined. Results and Discussion. The Antonivka and Tobak varieties demonstrated the highest ability to maintain growth after exposure to high temperatures; the Darynka Kyivska and Lira Odeska varieties were medium resistant. In the Doskonala, Bogdana and Avgustina varieties, a strong inhibition of shoot and root growth after heat stress was noted. In Antonivka, after high-temperature exposure, the O2•‒ generation increased slightly, while the content of H2O2 and LPO products did not change. In Tobak, Darynka Kyivska and Lira Odeska, the stress-induced increase in ROS formation and accumulation of LPO products was moderate. The hyperthermia-sensitive Doskonala, Bogdana and Avgustina showed a significant development of oxidative stress. Heat-resistant varieties had high catalase activity and increased total soluble carbohydrate content under heat stress. After exposure to high temperature, the proline content increased in all studied varieties, but no positive correlation was recorded between its amount and their heat resistance. Likewise, no significant correlation was found between the guaiacol peroxidase activity and the ability of varieties to maintain growth after heat stress. Conclusion. The high-level inverse correlation between catalase activity, soluble carbohydrate content, and the manifestation of oxidative stress effect indicates a significant contribution of these stress-protective system components to the adaptation of seedlings to heat stress. Indicators of the oxidative stress intensity and the functioning of individual components of the antioxidant system can be used to assess the heat resistance of wheat varieties at the early stages of development.