Peroxidation Processes Research Articles

Characterization of lipid peroxidation processes and antioxidant defense in parturients with COVID-19

Aim. The aim of the study was to investigate the functional state of the «lipid peroxidation - antioxidant defense» system in the peripheral blood of parturients with mild and severe COVID-19.Materials and methods. This casecontrol study examined 95 parturients with confirmed COVID-19 diagnosis in the third trimester, divided into two groups based on the severity of the disease. Group 1a included parturients with severe COVID-19 (community-acquired pneumonia, n=48), while group 1b consisted of patients with mild COVID-19 (acute respiratory viral infection, n=47). The control group was composed of 45 parturients without a prior or current diagnosis of COVID-19. The average age of women in the study groups was 23.9±0.50 years, and 24.4±0.60 years in the control group (p>0.05). Peripheral venous blood served as the material for the study. Spectrophotometric methods were used to examine the concentrations of primary (diene conjugates - DC) and final (active thiobarbituric acid products - TBARS) products of lipoperoxidation. The content of 8-isoprostane, total antioxidant capacity of plasma components, and phospholipase A2 were investigated using enzymelinked immunosorbent assay (ELISA).Results. Study showed that parturients with severe COVID-19 had increased levels of phospholipase A2 by 2.1 times (p<0.001), oxidative stress markers: diene conjugate concentrations by 1.94 times (p><0.001), TBARS by 2.2 times (p><0.001), and 8-isoprostane by more than 2 times (p><0.001), along with a simultaneous decrease in the total antioxidant capacity of blood plasma components by 1.7 times (p><0.001) compared to the control group. In the group of parturients with mild COVID-19, the studied indicators changed less significantly. Conclusion. The study established the pathogenetic role of SARS-CoV-2 in disrupting the functional system of «lipid peroxidation - antioxidant defense» and the development of oxidative stress in parturients who had COVID-19 in the third trimester. A dependency of oxidative stress marker concentrations in peripheral blood on the severity of COVID-19 was identified. It was shown that COVID-19 in the third trimester of pregnancy is associated with high levels of phospholipase A2, an imbalance in the prooxidant-antioxidant system, characterized by a reduction in the level of total antioxidant capacity and an increase in oxidative modification products of biomolecules, expressed by the growth of DC, TBARS, and 8-isoprostane levels, leading to oxidative stress correlated with the severity of lung damage. Key words: COVID-19, parturients, lipid peroxidation, antioxidant defense, oxidative stress> ˂ 0.001), oxidative stress markers: diene conjugate concentrations by 1.94 times (p ˂ 0.001), TBARS by 2.2 times (p ˂ 0.001), and 8-isoprostane by more than 2 times (p ˂ 0.001), along with a simultaneous decrease in the total antioxidant capacity of blood plasma components by 1.7 times (p ˂ 0.001) compared to the control group. In the group of parturients with mild COVID-19, the studied indicators changed less significantly.Conclusion. The study established the pathogenetic role of SARS-CoV-2 in disrupting the functional system of «lipid peroxidation - antioxidant defense» and the development of oxidative stress in parturients who had COVID-19 in the third trimester. A dependency of oxidative stress marker concentrations in peripheral blood on the severity of COVID-19 was identified. It was shown that COVID-19 in the third trimester of pregnancy is associated with high levels of phospholipase A2, an imbalance in the prooxidant-antioxidant system, characterized by a reduction in the level of total antioxidant capacity and an increase in oxidative modification products of biomolecules, expressed by the growth of DC, TBARS, and 8-isoprostane levels, leading to oxidative stress correlated with the severity of lung damage.

Correlation between molecules, which reflect malfunctioning of cellular respiration, degree of oxidative stress, and glycated hemoglobin in retinopaties with type 2 diabetes

Introduction. The pathogenetic role of biochemical changes in the development of diabetic retinopathy (DR) is undoubted and determines the importance of studies that reveal metabolic disorders of both individual molecules and show the relationships between them. Because of some commonalities between tissue respiration, monosaccharide and tryptophan exchange, and activation of lipid peroxidation (LP), there is an interest in studying the relationship between metabolites of these pathways in retinopathy.Aim. The aim is to study the content of metabolites of the kynurenic pathway and intermediate product of lipid peroxidation in blood, and to reveal the correlation between them and glycated hemoglobin’s (HbA1c) level in retinopathy with type 2 diabetes.Materials and methods. The 1st group (control group) included 21 healthy people; the 2nd group included 21 people with «prediabetes», the 3rd group - 21 patients with type 2 diabetes, the 4th group - 63 people with type 2 diabetes and diabetic retinopathy (DR) of varying severity levels. The content of kynurenines in the blood plasma (kynurenine (KYN), 3-hydroxykynurenine (3-HKYN), kynurenic acid (KYNA)) of all participants, as well as the concentration of malondialdehyde (MDA) was determined by high-performance liquid chromatography using a Shimadzu LC-20 chromatograph (Japan). The level of glycated hemoglobin (HbA1c) was determined using Beckman Coulter AU 480 (USA) biochemical analyzer. The results were calculated using Jamovi program version 2.3.Results. In the group of people with «prediabetes», the values of all studied parameters in the blood plasma were increased in comparison with the control group. In the group of patients with type 2 diabetes, the levels of KYN, 3- НKYN and MDA significantly exceeded those in the group of people with «prediabetes». In the group of people with DR, all indicators remained high, the values of 3-НKYN and KYNA showed a statistical difference compared to the group of patients with diabetes. When conducting a correlation analysis, corellations were identified between the level of HbA1c on the one hand and the values of KYN (r=0.77; p ˂ 0.001), concentrations of 3-НKYN (r=0.80; p ˂ 0.001), KYNA (r= 0.72; p ˂ 0.001) and MDA (r=0.84; p ˂ 0.001) – on the other. There was a correlation between HbA1c level and fundus scale (r=0.82; p ˂ 0.001) and between concentrations (of 3-HKYN) and MDA (r=0.50; p=0.002).Conclusion. An increased level of glycosylated hemoglobin and lipid peroxidation products in the blood during retinopathy against the background of type 2 diabetes, an increase in the concentrations of KYN, 3-HKYN, KYNA, and the presence of correlations between these indicators serve as the basis for proving the relationship of uncontrolled hyperglycemia with changes in cellular respiration and the development of oxidative stress. Hypoxic effects and the accumulation of intermediate metabolic products of the kynurenine pathway contribute to progressive neurovascular damage to the retina, activation of lipid peroxidation processes and inflammation.

Co‐Catalyzed Peroxidation of Cyclic β‐Dicarbonyls

AbstractA Co‐catalyzed peroxidation of cyclic β‐dicarbonyls (cyclic 1,3‐diketones, 4‐hydroxy‐2(5H)‐furanones and Meldrum's acids) with TBHP has been disclosed. A series of the alkylperoxy derivatives of 4‐hydroxy‐2(5H)‐furanones and Meldrum's acids were synthesized in moderate to good yields (13–86 %). The functionalization of 4‐hydroxy‐2(5H)‐furanones by the tBuOO group was performed with high selectivity in the presence of the cocktail of reactive oxidizing species, including metal and radical intermediates. The key species in the peroxidation process are probably the tert‐butylperoxy radical or its Co(III) complex, which are generated from the Co(II)/TBHP system. Cycle cleavage, which would be expected for cyclic β‐dicarbonyls based on previous reports, was observed to a large extent only for cyclic 1,3‐diketones.

Plasma lipid profile and sex hormone levels in rabbits under paraceta-mol-induced oxidative stress

Changes in the redox balance at different levels, which lead to the accumulation of toxic radicals against the background of a decrease in the content of redox-active compounds, i.e., a state of oxidative stress (OS), are considered the leading pathogenetic factor in pathological conditions. Processes of peroxide oxidation of biological substrates, especially cell membrane lipids and lipophilic compounds have both regulatory and pathological effects in the body of animals and humans. For now, it remains relevant to establish the regularities of interaction of metabolism during OS development. Among the large number of existing OS models, attention is drawn to those that can be reproduced in clinical practice, as a complication of treatment measures or an error in the medical strategy, due to a constant influence on peroxidation processes in the body. Important among such means is paracetamol (acetaminophen, APAP) – one of the most common antipyretic and analgesic drugs. In addition to the known hepato-, nephro- and neurotoxic effects of its long-term and/or excessive use, there are data on reproductive toxicity and disorders of lipid metabolism. Therefore, the aim of our work was to determine the lipid profile and the level of sex hormones in male rabbits during paracetamol-induced OS. The study was performed on male rabbits of the Khila breed. According to the principle of analogs, a control group (n = 12) was formed, which were kept on a standard diet, and an experimental group (n = 12), whose animals were simulated the state of OS by oral injection of a solution of paracetamol with food at a dose of 300 mg/kg of weight body once during 21 days. The following results were obtained by determining the dynamics of changes in biochemical indicators in the rabbit body during chronic injection of paracetamol: in the rabbits of the experimental group, after the injection of paracetamol, the level of diene conjugates was 63.0 % higher, and the content of thiobarbiturate-active products was 1.26 times higher (P ˂ 0.05). A decrease in the activity of the antioxidant defence system was also noted – the amount of reduced glutathione decreased by 35.4 %, and the activity of superoxide dismutase decreased by 25.6 % (P ˂ 0.05). The obtained changes were consistent with the comprehensive indicator of total antioxidant activity, which on the 21st day of the experiment was 34.1 % lower than the values of the control group (P ˂ 0.05). At the same time, the level of steroid hormones also changed during the study – the level of total testosterone gradually decreased (on the 21st day – by 22.8 %, and at the end of the experiment – by 30.9 %, P ˂ 0.05), while the level of 17β-estradiol had an upward trend and on the 21st day was higher than the control indicators by 10.7 % (P ˂ 0.05). Significant changes in lipid metabolism were found in male rabbits – the total cholesterol content on the 21st day of the experiment exceeded the data of control animals by 25.3 %, the level of triacylglycerols – by 42.3 %, and the content of low-density lipoprotein cholesterol also increased by 1.1 times (P ˂ 0.05), and the high-density lipoprotein cholesterol level, on the contrary, was reduced by 17.0 % (P ˂ 0.05). In general, the obtained results indicate the relationship between the development of OS with changes in lipid metabolism and the balance of sex hormones, which allows us to use the model of paracetamol-induced OS in rabbits for further research.

The influence of fullerene C60 compounds on the processes of lipid peroxidation and the activity of the antioxidant system in the body of calves

The influence of fullerene C60 compounds on the processes of lipid peroxidation and the activity of the antioxidant system in the body of calves

MaiJiTong granule attenuates atherosclerosis by reducing ferroptosis via activating STAT6-mediated inhibition of DMT1 and SOCS1/p53 pathways in LDLR−/− mice

Background and PurposeAtherosclerosis is the primary pathological basis of cardiovascular disease. Ferroptosis is a regulated form of cell death, a process of lipid peroxidation driven by iron, which can initiate and promote atherosclerosis. STAT6 is a signal transducer that shows a potential role in regulating ferroptosis, but, the exact role in ferroptosis during atherogenesis remains unclear. The Traditional Chinese Medicine Maijitong granule (MJT) is used for treating cardiovascular disease and shows a potential inhibitory effect on ferroptosis. However, the antiatherogenic effect and the underlying mechanism remain unclear. In this study, we determined the role of STAT6 in ferroptosis during atherogenesis, investigated the antiatherogenic effect of MJT, and determined whether its antiatherogenic effect was dependent on the inhibition of ferroptosis. Methods8-week-old male LDLR−/− mice were fed a high-fat diet (HFD) at 1st and 10th week, respectively, to assess the preventive and therapeutic effects of MJT on atherosclerosis and ferroptosis. Simultaneously, the anti-ferroptotic effects and mechanism of MJT were determined by evaluating the expression of genes responsible for lipid peroxidation and iron metabolism. Subsequently, we reanalyzed microarray data in the GSE28117 obtained from cells after STAT6 knockdown or overexpression and analyzed the correlation between STAT6 and ferroptosis. Finally, the STAT6−/− mice were fed HFD and injected with AAV-PCSK9 to validate the role of STAT6 in ferroptosis during atherogenesis and revealed the antiatherogenic and anti-ferroptotic effect of MJT. ResultsMJT attenuated atherosclerosis by reducing plaque lesion area and enhancing plaque stability in both preventive and therapeutic groups. MJT reduced inflammation via suppressing inflammatory cytokines and inhibited foam cell formation by lowering the LDL level and promoting ABCA1/G1-mediated lipid efflux. MJT ameliorated the ferroptosis by reducing lipid peroxidation and iron dysregulation during atherogenesis. Mechanistically, STAT6 negatively regulated ferroptosis by transcriptionally suppressing SOCS1/p53 and DMT1 pathways. MJT suppressed the DMT1 and SOCS1/p53 via stimulating STAT6 phosphorylation. In addition, STAT6 knockout exacerbated atherosclerosis and ferroptosis, which abolished the antiatherogenic and anti-ferroptotic effects of MJT. ConclusionSTAT6 acts as a negative regulator of ferroptosis and atherosclerosis via transcriptionally suppressing DMT1 and SOCS1 expression and MJT attenuates atherosclerosis and ferroptosis by activating the STAT6-mediated inhibition of DMT1 and SOCS1/p53 pathways, which indicated that STAT6 acts a novel promising therapeutic target to ameliorate atherosclerosis by inhibiting ferroptosis and MJT can serve as a new therapy for atherosclerosis treatment.

Lipid Peroxidation in Muscle Foods: Impact on Quality, Safety and Human Health.

The issue of lipid changes in muscle foods under the action of atmospheric oxygen has captured the attention of researchers for over a century. Lipid oxidative processes initiate during the slaughtering of animals and persist throughout subsequent technological processing and storage of the finished product. The oxidation of lipids in muscle foods is a phenomenon extensively deliberated in the scientific community, acknowledged as one of the pivotal factors affecting their quality, safety, and human health. This review delves into the nature of lipid oxidation in muscle foods, highlighting mechanisms of free radical initiation and the propagation of oxidative processes. Special attention is given to the natural antioxidant protective system and dietary factors influencing the stability of muscle lipids. The review traces mechanisms inhibiting oxidative processes, exploring how changes in lipid oxidative substrates, prooxidant activity, and the antioxidant protective system play a role. A critical review of the oxidative stability and safety of meat products is provided. The impact of oxidative processes on the quality of muscle foods, including flavour, aroma, taste, colour, and texture, is scrutinised. Additionally, the review monitors the effect of oxidised muscle foods on human health, particularly in relation to the autooxidation of cholesterol. Associations with coronary cardiovascular disease, brain stroke, and carcinogenesis linked to oxidative stress, and various infections are discussed. Further studies are also needed to formulate appropriate technological solutions to reduce the risk of chemical hazards caused by the initiation and development of lipid peroxidation processes in muscle foods.

New opportunities for correction of hormonal disorders and oxidative stress in women with genital endometriosis

Background. Genital endometriosis is one of the most urgent problems of modern gynecology. Considering oxidative stress as a pathogenetic link of endometriosis, we believe it reasonable to use a combined drug containing superoxide dismutase, resveratrol, and zinc. The purpose of the work was to evaluate the effectiveness of the treatment for genital endometriosis supplemented with the use of superoxide dismutase, resveratrol, and zinc, taking into account the leading pathophysiological links of the pathology. Materials and methods. Thirty-seven women of reproductive age with genital endometriosis were under observation. Treatment in the first group was carried out in accordance with the Guideline Development Group recommendations. Thirty-nine women of the second group additionally received a drug containing superoxide dismutase, resveratrol, and zinc. The control group included 30 healthy women. The state of lipid peroxidation processes was assessed by the level of diene conjugates and malondialdehyde in the blood serum and the antioxidant defense system by the content of superoxide dismutase and glutathione peroxidase. To monitor the patients’ quality of life, pain syndrome was studied using the Visual Analogue Scale. Statistical processing of the obtained data was carried out by means of the standard StatSoft Statistica for Windows 13.0 program pac­kage. Results. The assessment of the pain syndrome in the second group showed that it completely disappeared in women with the first stage of the disease. Among patients with the second stage, pain disappeared in 8 cases, 3 patients had a decrease from severe to mild pain. At the third stage, pain disappeared completely in 5 women, in 4 cases, it decreased from severe to mild, and in one woman, the pain decreased from unbearable to mild. All patients of the second group noted a decrease in pain during intercourse, and in the first stage — its absence, an increase in work capacity (r = 0.64, p < 0.01), a decrease in irritability and anxiety in the perimenstrual period (r = –0.59, p < 0.05) and overall satisfaction with the treatment result. Side effects were not noted in any of the patients. Conclusions. Improving treatment for genital endometriosis by supplementing therapy with superoxide dismutase, resveratrol, and zinc is pathogenetically justified, as it has a significant positive effect on the lipid peroxidation and antioxidant defense system, compared to the traditional treatment regimen.

EFFECT OF ACTG(4-7)-PRO-GLY-PRO AND ACTG(6-9)-PRO-GLY-PRO ON THE INTENSITY OF REDOX PROCESSES AND BEHAVIOURAL STATUS OF RATS UNDER THYROID HYPERFUNCTION CONDITIONS

The aim of the work is to study the effect of melanocortins on the intensity of redox processes in the prefrontal region of the brain and the behavioral status of rats against the background of thyroid hyperfunction. Material and methods. In the experiment, the test animals were divided into the following groups (n = 10): intact rats (control); animals treated with sodium salt pentahydrate L-thyroxine (hyperthyroidism); rats receiving ACTH (4-7)-Pro-Gly-Pro and individuals receiving ACTH (6-9)-Pro-Gly-Pro, re-spectively, intraperitoneally daily for 21 days, starting from day 22 of administration of sodium salt pentahydrate L-thyroxine. Hyperthyroidism was simulated in animals by intragastric administration of L-thyroxine sodium salt pentahydrate for 42 days. The intensity of lipoperoxidation processes was studied by the content of diene and triene conjugates in the prefrontal zone tissue, the initial level of TBА-reactive products, and the rates of spon-taneous and ascorbic peroxidation of lipids. The level of protein peroxidation products was determined by the reaction of oxidized amino acid residues of proteins with 2,4-dinitrophenyl hydrazone. Evaluation of the enzymatic unit of the antioxidant system of the prefrontal region was carried out by de-termining the activity of superoxide dismutase and catalase. The behavioral status of laboratory rodents was studied using the «Hole board» test. Results. The use of ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro compounds under experimental hyperthyroidism led to a decrease in the intensity of the processes of peroxidation of lipids, proteins and the restoration of levels of activity of antioxidant enzymes – superoxide dismutase and catalase in the tissue of the prefrontal region of the brain of animals, as well as correction behavioral indicators in the «Hole board» test. Conclusion. The obtained experimental data indicate that ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro show antiperoxy and antioxidant activity against lipoperoxidation parameters and oxidative modification of proteins and enzymatic protection systems in the prefrontal brain zone tissue, as well as exert psychocorregating action on behavioral responses of white rats against the background of thyroid hyperfunction.

СИНТЕЗ НОВЫХ О-ТИЕТАНЗАМЕЩЕННЫХ АЦЕТАМИДНЫХ ПРОИЗВОДНЫХ 6-МЕТИЛ-2-ТИОПИРИМИДИНА, ОБЛАДАЮЩИХ АНТИОКСИДАНТНОЙ АКТИВНОСТЬЮ

Aim: As is known, in connection with the observation of this trend in the world, currently many factors have a negative impact on the human body, provoking the production of reactive oxygen species, triggering the process of lipid peroxidation, which leads to the development of tumor, inflammatory processes, and the onset of aging of the body. Therefore, the search for new substances with antioxidant activity is relevant in modern pharmacy. Purpose: Synthesis of new O-thietane-substituted acetamide derivatives of 6-methyl-2-thiopyrimidine with antioxidant activity. Materials and Methods: New derivatives were obtained as a result of thiethanylation of the reaction products of ethyl 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetate with aliphatic and alicyclic amines. The structure of the obtained biologically active substances was confirmed using standardized methods of physicochemical analysis. Individuality was controlled by thin layer chromatography. Conclusions: Methods for the synthesis of new O-thietane-substituted acetamide derivatives of 6-methyl-2-thiopyrimidine have been developed, and the antioxidant activity of the resulting compounds has been analyzed. Some structure-activity patterns of the synthesized compounds have been established.

Magnetic manipulation of the reactivity of singlet oxygen: from test tubes to living cells.

Although magnetism undoubtedly influences life on Earth, the science behind biological magnetic sensing is largely a mystery, and it has proved challenging, especially in the life sciences, to harness the interactions of magnetic fields (MFs) with matter to achieve specific ends. Using the well-established radical pair (RP) mechanism, we here demonstrate a bottom-up strategy for the exploitation of MF effects in living cells by translating knowledge from studies of RP reactions performed in vitro. We found an unprecedented MF dependence of the reactivity of singlet oxygen (1O2) towards electron-rich substrates (S) such as anthracene, lipids and iodide, in which [S ˙+ O2 ˙-] RPs are formed as a basis for MFs influencing molecular redox events in biological systems. The close similarity of the observed MF effects on the biologically relevant process of lipid peroxidation in solution, in membrane mimics and in living cells, shows that MFs can reliably be used to manipulate 1O2-induced cytotoxicity and cell-apoptosis-related protein expression. These findings led to a 'proof-of-concept' study on MF-assisted photodynamic therapy in vivo, highlighting the potential of MFs as a non-invasive tool for controlling cellular events.

Correlation between Oxidative Stress Markers and Periodontal Disease in Dogs.

In dogs, periodontal disease (PD) is a highly common condition whose prevalence rises significantly with age. Studies on rats with experimentally induced PD and human clinical trials have found an association between oxidative stress (OS) and PD, as has been observed in many other inflammatory disorders. The objective of this research was to assess the main indicators of oxidative stress detected in the saliva of dogs and to compare them to the degree of inflammation and tartar amount on their teeth and gums. By identifying these correlations, we intended to identify early-stage PD markers that would allow us to diagnose the condition in dogs without requiring for invasive or traumatic procedures. The antioxidant enzyme superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA) and 8-hydroxyguanosine (8OHG), matrix metalloproteinase-8 (MMP8), and the quantity of total proteins are the markers that have been investigated in order to accomplish these objectives. The appearance of specific forms of periodontal disease has been confirmed by an increase in the saliva concentration of MMP8, a marker commonly used in the diagnosis of these pathologies in humans. The study was carried out on 22 dogs divided in a control group (C) and study groups (S), the second one being divided into three subgroups according to the severity of the gum inflammation and the presence or absence of tartar: S1-small accumulation of tartar, lack of infection-related signs; S2-moderate accumulation of tartar, gums swollen, red, and bled easily; S3-significant accumulation of tartar; gums bright red and bleeding; marked pain and halitosis. A correlation between the concentration of the tested parameters and the severity of the local appearance of the gum and teeth was noted. In comparison to the results of individuals from the control group, MMP8 reported increases of 1.2, 2, and 3.7 times, respectively, in the case of individuals from subgroups S1, S2, and S3. Oxidative stress is caused by inflammatory processes in the oral cavity. The presence of oxidative stress was demonstrated by the evaluation of different indicators in the saliva: an increase in the general antioxidant status, which was associated with an increase in SOD activity; intensification of the lipid peroxidation processes, as demonstrated by the accumulation of the MDA peroxidation product; and an increase in the DNA oxidation processes, as demonstrated by the accumulation of the oxidation product 8OHdG. In consequence, it was observed that there were up to 2-fold increases in protein levels, total antioxidant activity, SOD, and MDA, and up to 8.6-fold increases in the case of 8-OHdG when comparing dogs from the S3 group (significant tartar accumulation; bright red and bleeding gums; marked pain and halitosis) to those in the control group.

Parameters of oxidative, nitrasive and anti-oxidative status in men with erectile dys-function due to combat trauma

The development of oxidative and nitrative stress and the processes of free radical oxidation are associated with many pathological processes. Damage of any origin leads to the activation of free radical processes not only in the place of damage, but also in the whole organism. The aim of the study is to assess the state of lipid peroxidation, content of GSH and GSSG and the activity of NO-synthase and arginase in lymphocytes and peripheral blood serum in men with erectile dysfunction due to combat trauma. The research was conducted on peripheral blood lymphocytes of men injured as a result of combat operations (shrapnel and bullet wounds) in the Russian-Ukrainian war, and who were treated at the Military Medical Clinical Center of the Western Region (Lviv, Ukraine). The research group of men with combat injuries was divided into two age groups: men aged 20–39 years and men aged 40–53 years. The MDA content in the blood serum of patients of both age groups was 1.35 times higher than in the control group. In peripheral blood lymphocytes, the MDA content in patients of the young age group was 1.27, and in patients of the middle age group in 1.39 times higher than in the control group. Simultaneously, no significant changes in the concentration of oxidized glutathione in blood serum and blood lymphocytes were found between men with erectile dysfunction due to combat trauma and healthy men. GSH content in blood serum in patients of both age groups was significantly lower than in the control group. The arginase/NOS ratio in blood serum was 9.75 times lower in the young age group and in 20.45 times lower in the middle age group compared to healthy men. It was established that in the blood serum and blood lymphocytes of men with erectile dysfunction due to combat trauma, processes of lipid peroxidation were intensified and the GSH level was reduced. The GSH/GSSG ratio was reduced only in blood serum. It was found that the oxidative stress is associated with development of nitrative stress. The arginase/NOS ratio was shifted towards increased NOS activity. Activation of iNOS was accompanied by significant inhibition of cNOS. Further study of biochemical mechanisms is important to understand the triggers of erectile dysfunction due to combat trauma.

Ethyl acetate extract of breadfruit leaves (Artocarvus altilis) improves lipid profile and reduces F2-isoprostane in dyslipidemia-induced Wistar rats (Rattus norvegicus)

Dyslipidemia is closely related to the process of lipid peroxidation. In the non-enzymatic peroxidation process of arachidonic acid, an esterification process occurs and produces a metabolite in the form of isoprostane. The most common isoprostane found is F2-isoprostane. In traditional medicine, breadfruit leaves (Artocarvus altilis) have been widely used due to their antioxidant compounds, such as flavonoids, phenols, tannins, saponins, and other secondary metabolites. This study aims to evaluate the activity of breadfruit leaf ethyl acetate extract in improving the lipid profile and F2-isoprostane in dyslipidemia-induced Wistar rats (Rattus norvegicus). This study was an experimental study with a pretest-posttest control group design with two treatment groups: fenofibrate 1.65 mg (P1) and breadfruit leaf ethyl acetate extract (760 mg) (P2) for 28 days. Total cholesterol, triglyceride, HDL, LDL, and F2-isoprostane levels were measured before and after treatment expressed in mg/dL. The data were analyzed using a parametric t-paired and t-unpaired test with a 95% confidence level. The study found that breadfruit leaf extract was better than fenofibrate at lowering total cholesterol (pre 172.41 ± 4.93; post 101.24 ± 2.09), triglycerides (pre 172.41 ± 4.93; post 101.24 ± 2.09), LDL (pre 95.78 ± 8.00; post 12.03 ± 10.06), F2-Isoprostane (pre 924.86±10.40; post 432.99±14.17), and raising HDL (pre 102.29 ± 10.40; post 143.89 ± 5.99). In conclusion, ethyl acetate extract is better than fenofibrate in improving lipid profiles and reducing F2-isoprostane in dyslipidemia-induced animal tests.
 Keywords: breadfruit leaves (Artocarvus altilis), dyslipidemia, F2-Isoprostane, fenofibrate, lipid profile, total cholesterol

P53 Regulation upon Lipid Peroxidation and Ferroptosis for Intervention against Atherogenesis

Abstract: Tumor protein 53 (P53), as an intracellular regulator of antioxidant responses, participates in the expression of antioxidant defense and lipid metabolism as well as the synthesis of genes in cells. The balance of oxidation and reduction can be disrupted by many pathological conditions, and the role of the antioxidant system in protecting the equilibrium state from pathological effects, such as reactive lipids, is crucial. In particular, the excessive accumulation of lipid peroxidation products is a key factor driving the occurrence and development of various diseases. Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death cascade reaction, which has become a key research area in cardiovascular diseases. Atherosclerosis (AS) is a pathological change caused by lipid metabolic disorder, inflammatory response, and endothelial cell injury, and is the most common cause of cardiovascular disease. This review briefly outlines lipid peroxidation and key components involving ferroptosis cascade reactions, summarizes and emphasizes the role of P53-related signaling pathways in mediating lipid peroxidation and ferroptosis, and focuses on the known P53 target genes that regulate these pathways, as well as explores the possibility of P53 intervention in the treatment of AS by regulating lipid peroxidation and ferroptosis processes.

Modelling the redox imbalance and oxidative stress in the hippocampus at aluminum neurotoxicity and initiating the coenzyme А biosynthesis

An Alzheimer-like pathological process was induced in mature female Wistar CRL: (WI) WUBR rats using aluminum chloride (200 mg/kg, intragastrically, 6 weeks) in order to model redox imbalance and oxidative stress (OS) in the hippocampus and study the possibilities of their correction 2 weekly administration of coenzyme A biosynthesis modulators (panthenol – PL, pantethine – PT, homopantothenate – HP) at a dose of 200 mg/kg intragastrically for 2 weeks). Against the background of activation of peroxidation processes and a decrease in acetylcholinesterase activity, a decrease in the reduction potential of glutathione and the level of the acid-soluble fraction of CoA was observed with a simultaneous increase in the activity of glutathione-metabolizing enzymes (GR, GPx, GST), the process of S-glutathionylation of proteins and the level of protein thiols. The consumption of the precursors of CoA biosynthesis in full (PL, PT) or in part (HP) had an antioxidant effect, restored the activity of AChE, the level and reduction potential of glutathione and glutathione-metabolizing enzymes, the process of S-glutathionylation, and stimulated the activity of enzymes generating NADPH+. Taking into account the low modulating effect of coenzyme precursors on the level of CoA in the hippocampus and their high redox pharmacological activity, their non-coenzymatic effect on redox mechanisms leading to an increase in the bioavailability of reducing equivalents and energy status is assumed.

In vivo comparison of antioxidant properties of fucoidan from Fucus vesiculosus after intragastric administration and external application

Fucoidans are sulfated heteropolysaccharides from brown seaweed, known for anticoagulant, anti- inflammatory, antiviral and other properties. The method of administration and the dosage form of the medicinal substance have a significant impact on the bioavailability of the drug, as well as on its metabolism in the body.The purpose of the work was to evaluate the effect of fucoidan from Fucus vesiculosus on the indicators of the antioxidant system in mice with experimental streptozotocin-induced diabetes when administered intragastrically and externally.To evaluate the antioxidant properties of fucoidan in vivo , diabetes mellitus was developed in mice by intraperitoneal administration of streptozotocin and a 1% solution of nicotinic acid. Fucoidan in two dosage forms was administered for 10 days after the formation of the pathology at a dose of 50 mg/kg in the form of tablets intragastrically and 10 mg per animal in the form of an ointment when applied externally. To assess the antioxidant status of animals, the concentration of thiobarbituric acid-reactive products (TBA-RP) in the blood plasma, the level of reduced glutathione (GSH) and catalase activity (CAT) in the erythrocytes were determined.In mice with streptozotocin-induced diabetes against the background of pathology, the process of lipid peroxidation intensified and the effectiveness of the antioxidant system decreased. Fucoidan from F. vesiculosus suppresses systemic oxidative stress in mice with induced type 2 diabetes mellitus. This is achieved due to the inhibition of excessive generation of pro-oxidants (TBA-RP) and a protective effect on the factors of the antioxidant defense system (catalase activity and glutathione content). To the greatest extent, fucoidan, when administered intragastrically, prevents the formation of pro-oxidants, while when applied externally, it has a protective effect to a greater extent due to the activation of antioxidants.

Copper metabolism in osteoarthritis and its relation to oxidative stress and ferroptosis in chondrocytes.

Ferroptosis, an iron-ion-dependent process of lipid peroxidation, damages the plasma membrane, leading to non-programmed cell death. Osteoarthritis (OA), a prevalent chronic degenerative joint disease among middle-aged and older adults, is characterized by chondrocyte damage or loss. Emerging evidence indicates that chondrocyte ferroptosis plays a role in OA development. However, most research has concentrated on ferroptosis regulation involving typical iron ions, potentially neglecting the significance of elevated copper ions in both serum and joint fluid of patients with OA. This review aims to fill this gap by systematically examining the interplay between copper metabolism, oxidative stress, ferroptosis, and copper-associated cell death in OA. It will provide a comprehensive overview of copper ions' role in regulating ferroptosis and their dual role in OA. This approach seeks to offer new insights for further research, prevention, and treatment of OA.

Characteristics of lipid peroxidation processes and factors of the antioxidant defense system in chronic rhinitis

To study the state of the processes of lipid peroxidation and antioxidant protection in various types of chronic rhinitis. The study included 50 patients with CR, of which 21 were with chronic allergic rhinitis (CALR), 20 with chronic vasomotor rhinitis (CVR), 9 with chronic atrophic rhinitis (CAR). The control group was represented by 50 practically healthy volunteers with no otorhinolaryngological complaints. The indicators of the LPO-AOD system in erythrocytes were evaluated by spectrophotometric methods. Statistical data processing was carried out using the Statistica 7.0 software package (StatSoft, USA). In all patients with CR in the blood erythrocytes, an increase in the level of malondialdehyde (MDA), a decrease in the activity of superoxide dismutase (SOD), catalase (CAT) relative to the control group was found. With CAR, the most pronounced changes are determined, with CVR - minimal. In patients with CR, lipid peroxidation is activated, MDA increases by 1.29 times, by 1.37 times with CAR, and by 1.31 times with CALR relative to normal values. The activity of the antioxidant system decreases, which reflects the classical variant of inhibition of antioxidant enzymes: SOD is reduced by 1.08 times in CAR, by 1.07 times in CALR, and 1.04 times in CVR, CAT in CAR is reduced by 1.02 times; CALR by 1.02 times, with CVR by 1.01 times. The coefficient of oxidative stress with CVR is 1.36, with CAR is 1.5, with CALR is 1.42. In CR, the predominance of pro-oxidant processes over antioxidant ones is revealed, a slight oxidative stress is detected, probably due to the presence of hypoxia and intoxication syndrome. An in-depth study of lipid peroxidation processes and factors of the antioxidant defense system, depending on the CR phenotype, can be used to correct therapy and prevent exacerbations, as well as markers of progression and prognosis of chronic rhinitis.

Design and synthesis of guaiacol-based fibrate derivatives with potential hypolipidemic and liver protective actions

Hypolipidemic and hepatoprotective effectives of the newly synthesized guaiacol-based fibrate derivatives were evaluated in Triton WR-1339-induced hyperlipidemic mice. All the target compounds were preliminary screened, in which compound T5 showed significant hypolipidemic effects, decreasing triglycerides (TG) and total cholesterol (TC), which was better than the positive drug clofibrate. Furthermore, compound T5 has a dose-dependent effect on the blood lipid lowering activity of hyperlipidemia mice, and hepatic transaminases (AST and ALT) induced by hyperlipidemia have a significant improvement effect. Histological examination of the liver of hyperlipidemic mice supplemented with T5 revealed a significant amelioration in hepatic lipid accumulation when compared with the effect of the positive drug clofibrate. The mechanism of lipid-lowering showed that T5 could significantly increase the expression of PPAR-α protein in the liver of hyperlipidemic mice. In addition, T5 can also improve the lipid peroxidation process induced by hyperlipidemia, reducing the level of malondialdehyde (MDA). These findings reinforced the effects of T5 as a hypolipidemic candidate compound with liver protective activity.