Levels Of Conjugated Dienes Research Articles

INSIGHTS INTO THE MOLECULAR AND BIOCHEMICAL ROLE OF QUINIC ACID IN ALLEVIATING ETHANOL-INDUCED LIVER TOXICITY IN A RAT MODEL: EXPLORING OXIDATIVE STRESS, INFLAMMATION, AND APOPTOSIS SIGNALING PATHWAYS

Objective: The study aimed to evaluate the effects of quinic acid, a natural bioactive compound, on tissue and circulatory antioxidant status, lipid peroxidation, and its anti-apoptotic and anti-inflammatory mechanisms in ethanol-induced hepatotoxicity in rats. Methods: The rats were divided into four groups. Groups 1 and 4 were administered isocaloric glucose. Groups 2 and 3 received 30% ethanol at a dose of 5 g/kg body weight daily. In addition, Groups 3 and 4 were treated with quinic acid (50 mg/kg body weight) dissolved in 2% dimethyl sulfoxide. Results: The results demonstrated significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxides (LOOH), along with significantly reduced enzymatic and non-enzymatic antioxidant activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione-related enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST), as well as reduced levels of glutathione (GSH), Vitamin C, and Vitamin E in ethanol-treated rats compared to the control group. Administration of quinic acid to rats with ethanol-induced liver injury significantly reduced the levels of TBARS, LOOH, and CD while markedly increasing the activity of SOD, CAT, GPx, GR, GST, and levels of GSH, Vitamin C, and Vitamin E in liver tissues compared to untreated ethanol-exposed rats. In addition, ethanol-treated rats showed increased mast cell accumulation, which was reduced by quinic acid treatment, along with elevated expressions of inflammatory and apoptotic markers, including Bax, Caspase-9, tumor necrosis factor-alpha, Nuclear factor kappa B, and interleukin-6, and a decreased expression of Bcl2 in the liver. Quinic acid supplementation in ethanol-fed rats reversed these ethanol-induced changes. Immunohistochemical studies further supported these findings. Conclusion: Quinic acid, with its antioxidant, anti-inflammatory, and anti-apoptotic properties, may offer a therapeutic option for protecting against ethanol-induced hepatotoxicity

LIPID PEROXIDATION PRODUCTS AND FREE FATTY ACIDS IN BLOOD PLASMA AND CEREBRAL SPINAL FLUID IN CHILDREN WITH CONVULSIVE SYNDROME

Objective: This study aims to investigate the levels of lipid peroxidation (LP) products and free fatty acids (FFA) in children with convulsive syndrome (CS) to understand the oxidative stress associated with seizures. Method: A total of 45 children aged from several months to 1.5 years with various forms of CS were analyzed, alongside a control group of 13 healthy adults. Blood plasma and cerebrospinal fluid (CSF) were collected, and the concentrations of LP products (diene conjugates and Schiff bases) and FFA were quantified using spectrophotometric and fluorometric methods. Results: The findings revealed that children with CS exhibited significantly elevated levels of diene conjugates (810 ± 150 nmol per 1 mg lipids) and Schiff bases (42.6 ± 5.5% per 1 mg lipids) in blood plasma compared to the control group. Additionally, FFA levels in the blood plasma (2.1 ± 0.4 µg per 1 mg protein) were found to be markedly higher than those in healthy adults. These results indicate a profound increase in oxidative stress in children with CS, correlating with the duration and type of seizures. Novelty: This study highlights the critical role of oxidative stress in pediatric convulsive disorders and suggests that incorporating antioxidant therapies, such as α-tocopherol, may improve treatment efficacy in these patients. The findings provide a foundation for further research into therapeutic strategies targeting oxidative stress in pediatric neurology.

Effects of Dihydroquercetin on the Intensity of Oxydative Stress in Rat Liver Mitochondria at Hypothermia

A decrease in body temperature in homeothermic animals can cause a state of the body called hypothermic. It is accompanied by the development of a number of pathological processes, many of which are associated with mitochondrial dysfunction and the development of oxidative stress. In connection with the widespread introduction of hypothermia into medical practice, the question of the possibility of a regulatory influence on the proxidant-antioxidant status of mitochondria at low body temperatures remains relevant. In recent years, plant polyphenols, in particular dihydroquercetin (DHQ), have gained wide popularity as therapeutic agents with antioxidant and membrane protective effects. In this work, we investigated the effects of DHQ on the intensity of oxidative stress in rat liver mitochondria under moderate hypothermia. It was found that a course (5 days) oral administration of DHA at a dose of 100 mg/kg significantly reduces the levels of LPO and OMP products in the liver mitochondria of control rats, increasing the content of non-enzymatic components of the thiol-disulfide antioxidant system`s. DHQ effectively protects liver mitochondria from the development of oxidative stress during hypothermia, as evidenced by a significant decrease (and in some cases, complete normalization) in the levels of diene conjugates, MDA, Schiff bases and carbonyl groups in a group of animals subjected to hypothermia with prior administration of this polyphenol. At the same time, DHQ significantly increases the levels of glutathione and vitamin E, and also normalizes the content of thiol groups in mitochondrial proteins. In vitro, DHQ exhibits a dose-dependent antioxidant effect, suppressing OMB in mitochondria incubated in Fenton's medium (IC50 = 0.160 mg/ml).

Metabolic and genetic basis of liver damage in mechanical jaundice of non-tumor genesis in obstractive cholangitis or biliary pancreatitis

Aim. Establishment of versatile mechanisms behind liver damage in mechanical jaundice of non-tumor genesis combined with acute obstructive cholangitis or acute biliary pancreatitis.Materials and methods. In total, 64 cases of mechanical jaundice developed against the background of cholelithiasis were studied. Group 1 included 30 patients with mechanical jaundice combined with cholangitis; group 2 included 34 patients with acute biliary pancreatitis. Bile duct reconstruction was performed by an open method followed by standardized treatment. The intensity of membrane lipid peroxidation was determined by the level of diene conjugates, malonic dialdehyde, superoxide dismutase activity, and the activity of phospholipase A2. The severity of endotoxemia was estimated; a molecular-genetic test of the polymorphism of antioxidant system genes was performed.Results. The significance of the gene polymorphism of antioxidant enzymes in the formation of systemic alterative phenomena and severity of liver damage in mechanical jaundice complicated by cholangitis or acute pancreatitis was determined by allocation of patient subgroups depending on the presence of mutant allele T in the gene of superoxide dismutase SOD2 (C1147T). The groups of patients with the presence of such polymorphism, regardless of the combined diseases, demonstrated more pronounced and prolonged liver functional disorders and homeostasis disorders after restoration of biliary tract patency.Conclusion. The presence of mutant alleles of the SOD2 gene (C47T) in patients with non-tumor mechanical jaundice combined with acute cholangitis or pancreatitis is associated with an increase in the intensity of damage mechanisms at the systemic level, primarily with membrane lipid peroxidation, which correlates with the severity of liver damage (r = 0.834–0.967; p < 0.05).

Intensity of lipid peroxidation processes in the blood of dogs infected with the causative agent of toxocariasis

Gastrointestinal helminthiasis, particularly toxocarosis, is the most common invasive disease of dogs in our country and abroad. It is important to note that toxocarosis is a zoonosis that poses a threat not only to animals but also to humans. It is known that one of the manifestations of the toxic effect of toxocar byproducts is the activation of the processes of peroxide oxidation of cell membrane lipids. Lipid peroxidation is one of the most essential oxidation processes in the body of dogs. Currently, this process is considered one of the leading causes of cell damage and death due to the negative effect of reactive oxygen species. Any sufficiently powerful impact on the animal body, including the development of toxocarosis, can initiate lipid peroxidation processes. That is why the work aimed to determine the effect of toxocarosis infestation on the level of intermediate and final products of lipid peroxide oxidation in the body of dogs. 12 dogs aged two to four months were used for experimental research, and two groups of six animals each were formed: control and experimental. Puppies of the control group were clinically healthy. Puppies of the research group were experimentally infected with the causative agent of toxocarosis at a dose of 5,000 invasive T. canis eggs per kg of body weight. The development of toxocarosis in dogs leads to a significant and probable (P < 0.001) accumulation in the blood of dogs in all periods of the study of the content of intermediate (diene conjugates) and final (TBK-active products) products of lipid peroxidation. In dogs with experimental toxocarosis, an increase in these LPO products was established, especially on the 28th and 35th days of the experiment, where, accordingly, the level of diene conjugates ranged from 0.750 ± 0.004 to 0.675 ± 0.003 odA/ml (Р < 0.001), and the level of TBC-active products - in the range of 38.38 ± 0.174 – 38.18 ± 0.137 μmol/l (Р < 0.001). These changes may be because, in the pathogenesis of toxocariasis in dogs, an important role is played by the increased formation of reactive oxygen species, which subsequently cause a disturbance in the balance between the content of oxidants and antioxidants in the body of dogs. It is also worth paying attention to more significant changes in the level of intermediate POL products in dogs' blood during experimental toxocarosis compared to the final products.

Значення порушень прооксидантно- антиоксидантних процесів у патогенезі розвитку експериментальної пневмонії та адреналінового пошкодження міокарда

Today, pneumonia is one of the most common diseases of the respiratory system, accounting for 35-45%. No less common is coronary heart disease (CHD) among the pathologies of the cardiovascular system. In the medical world, the problem of comorbid pathology is acute, which can reduce adaptive capabilities, reduce the effectiveness of treatment and increase the development of various complications. Pathogeny of development of pneumonia and CHD is in this time to the end not studied. Research aim: to find out the features of changes and role of lipoperoxidation processes and state of the antioxidant system in pathogenesis of development of experimental pneumonia of connected with the adrenalin damage of myocardium. Materials and research methods. There were undertaken studies on 82 guinea-pigs (males), that distributed on three groups: the first group is intact animals – control (10); the second (experience) group is animals with experimental pneumonia (ЕP) accordingly on 1th, 3th, 6th and 14th twenty-four hours of experiment (36); the third (experience) group is animals with the united pathology (ЕP and adrenaline myocardium damage – AMD) accordingly on 1th, 3th, 6th and 14th twenty-four hours of experiment (36). The fixed twenty-four (1th, 3th, 6th and 14th twenty-four hours) hours took into account, because they answer the classic stages of the abrupt used for setting fire reply (incubations, development of illness, height of illness, convalescence) and motion. ЕP recreated by the method of Shlapnikov V. N., Solodova T. L. et al. by the way of intranasal infection of animals of Staphylococcus of aureus. AMD designed by non-permanent intramuscular introduction of 0,18% solution adrenaline hydrotartrate («Darnytsia», Ukraine), in a dose 0,5 mg/kg. Assessment of lipid peroxidation was carried out by measuring levels of diene conjugates (DC) and malonyldialdehyde (MDA), and activity of antioxidant system was evalution by catalase (CAT) and superoxide dismutase (SОD). Euthanasia by decapitation of laboratory animals was conducted under act of chloroform anaesthesia. Determinations of DC in fabrics of kidney was carred by Gavrilov's method, content of МDА – by the method of Y. N. Korobeynikov, activity SОD – by the method of R. Fried, CAТ – by the method of B. Holmes and C. Masters. The statistical working of the obtained data was carried out by Student's t-test. Results and discussions. ЕP and AMD (1th, 3th, 6th, 14th twenty-four hours) is accompanied by the increase of content of DC in fabrics of kidneys accordingly on 62,5 %, 71,5 %, 79,5 %, 82,9 % (р < 0,05), MDA – on 55,0 %, 62,1 %, 72,7 %, 85,7 % (р < 0,05) on a background the decline of activity of SОD accordingly on 25,2 %, 27,2 %, 30,6 %, 37,2 % (р < 0,05), CAT – on 31,2 %, 34,7 %, 40,3 % 45,5 % (р < 0,05) in relation to the control group of animals, that testified to development of oxidative stress, that strengthened motion of pneumonia and AMD. Conclusion: the results of researches are Got by us allow to assert that comorbidity (EP and AMD) predetermines violation of balance between prooxidant and by an antioxidant the systems, strengthening of lipoperoxidation processes in the conditions of depression of the antioxidant securing for all stages of their development with advantage on 6th and 14th twenty-four hours of experiment against the intact group of animals and specifies on the important role of one of molecular (lipid) mechanisms of damage of cages in pathogenesis of formation of these models of illnesses.

Protective role of S-adenosylmethionine on high fat/high cholesterol diet-induced hepatic and aortic lesions and oxidative stress in guinea pigs.

S-adenosylmethionine (SAM) is the main methyl group donor and has antioxidant potential. In this study, preventive and regressive potential of SAM were investigated in high fat/high cholesterol (HFHC) diet-induced non-alcoholic fatty liver disease (NAFLD) in guinea pigs. They were injected with SAM (50 mg/kg, i.p.) for 6 weeks along with HFHC diet or 4 weeks after HFHC diet. Serum transaminase activities, total cholesterol (TC), triglyceride (TG), cytochrome p450-2E1 (CYP2E1) and hydroxyproline (Hyp) levels, prooxidative and antioxidative parameters, protein expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) together with histopathological changes were examined in the liver. SAM treatment diminished HFHC diet-induced increases in serum transaminase activities and hepatic TC, TG, CYP2E1, Hyp, α-SMA and TGF-β1 expressions and ameliorated prooxidant-antioxidant balance. Histopathological scores for hepatic steatosis, inflammation, and fibrosis were decreased by SAM treatment. Increases in TC, diene conjugate levels, and lipid vacuoles within the tunica media of the aorta were reduced in HFHC-fed animals treated with SAM. These protective effects were also detected in the regression period of HFHC-guinea pigs due to SAM. In conclusion, SAM treatment was found to be effective in prevention and regression of HFHC-induced hepatic and aortic lesions together with decreases in oxidative stress in guinea pigs with NAFLD.

Transgenerational effect of prenatal stress on behavior and lipid peroxidation in brain structures of female rats during the estral cycle.

The effect of stress in pregnant female Wistar rats on the behavior and lipid peroxidation (LP) in the neocortex, hippocampus and hypothalamus in the female F2 generation during the ovarian cycle was investigated. We subjected pregnant females to daily 1-hour immobilization stress from the 15th to the 19th days of pregnancy. Further, family groups were formed from prenatally stressed and control male and female rats of the F1 generation: group 1, the control female and male; group 2, the control female and the prenatally stressed male; group 3, the prenatally stressed female and the control male; group 4, the prenatally stressed female and male. The females of the F2 generation born from these couples were selected into four experimental groups in accordance with the family group. At the age of 3 months, behavior of rats was studied in the "open field" test in two stages of the ovarian cycle - estrus and diestrus. After 7-10 days, the rats were decapitated and the neocortex, hypothalamus and hippocampus were selected to determine the level of diene and triene conjugates, Schiff bases and the degree of lipid oxidation (Klein index). In F2 females with one prenatally stressed parent, there was no interstage difference in locomotor-exploratory activity and anxiety. If both F1 parents were prenatally stressed, female F2 rats retained interstage differences similar to the control pattern, while their locomotor-exploratory activity and time spent in the center of an "open field" decreased in absolute values. In the neocortex of F2 females in groups with prenatally stressed mothers, the level of primary LP products decreased and the level of Schiff bases increased in the estrus stage. In the hippocampus of F2 females in the groups with prenatally stressed fathers, the level of Schiff bases decreased in the estrus stage, and the level of primary LP products increased in group 2 and decreased in group 4. In the hypothalamus of F2 females in the groups with prenatally stressed mothers, the level of Schiff bases increased in the estrus stage and decreased in the diestrus; in addition, in group 3, the level of primary LP products in the estrus stage increased. Thus, we demonstrated the influence of prenatal stress of both F1 mother and F1 father on the behavior and the level of LP in the neocortex, hippocampus and hypothalamus in female rats of the F2 generation in estrus and diestrus.

Saliva as a Diagnostic Tool for Early Detection of Exercise-Induced Oxidative Damage in Female Athletes.

Although blood still remains the most commonly utilized medium to detect increased levels of oxidative damage induced by exercise, saliva diagnostics have gained increasing popularity due to their non-invasive nature and athlete-friendly collection process. Given that the contribution of various phases of the menstrual cycle to the levels of oxidative damage may differ, the aim of this study was to evaluate an agreement between salivary and plasmatic levels of lipid peroxidation products in female swimmers in both the follicular (F) and luteal (L) phases of the menstrual cycle at rest and following exercise. Twelve well-trained female swimmers aged 19.6 ± 1.1 years old were examined. We measured diene conjugates (DCs), triene conjugates (TCs), and Schiff bases (SBs) in lipids immediately after their extraction from both saliva and blood plasma. All female swimmers were studied two times each, in the two different phases of one menstrual cycle, before and after high-intensity interval exercise (HIIE). Salivary and plasmatic levels of DCs, TCs, and SBs significantly increased post-exercise compared to pre-exercise, in both the F and L phases. A high positive correlation was observed between the concentrations of DCs, TCs, and SBs in the saliva and blood plasma of participants in the F and L phases, both at rest and following HIIE. Ordinary least products regression analysis indicates that there was no proportional and differential bias in the data. The Bland-Altman method also declares that there was no differential bias, since the line of equality was within the 95% confidence interval of the mean difference between salivary and plasmatic levels of DCs, TCs, and SBs in female swimmers, in both the F and L phases, before and after HIIE. There was also no proportional bias in the Bland-Altman plots. Thus, this is the first study to report a high agreement between the quantifications of DCs, TCs, and SBs in the saliva and blood plasma of female swimmers in both the F and L phases, at rest and following HIIE.

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.

Changes in Endogenous Intoxication and Antioxidant Defense System Markers in Patients with Tumor-Induced Acute Colonic Obstruction

A comprehensive evaluation of clinical and biochemical markers defining the status of endotoxemia in patients diagnosed with acute colonic obstruction (ACO) was conducted. The findings revealed that advancing stages of ACO corresponded to an increase in serum levels of endogenous intoxication markers and a simultaneous decrease in antioxidant defense system (ADS) markers.
 The aim of the study was to analyze changes in endogenous intoxication and ADS markers in patients with tumor-induced ACO throughout the disease progression and evaluate the outcomes.
 Materials and Methods. The study is based on examining serum levels of endogenous intoxication markers, including middle weight molecules (MWM), products of lipid peroxidation (LPO) - conjugated dienes (CD), malonaldehyde (MA), protein oxidative modification (POM), and key ADS markers, specifically superoxide dismutase (SOD), catalase (CAT), and ceruloplasmin (CP), in 155 patients with ACO throughout the disease progression and 20 apparently healthy individuals.
 Results. Upon patient admission to the hospital, the duration of ACO was found to correlate with an increase in endogenous intoxication markers and a decrease in antioxidant defense markers. Depending on ACO stage, MWM levels were 0.42 (0.38; 0.43) IU, 0.56 (0.51; 0.58) IU, and 0.72 (0.69; 0.73) IU, respectively (р1<0.01, р2<0.01, р3<0.01), with a normal range of 0.23 (0.18; 0.25) IU. In the compensated stage of ACO, MA levels significantly increased compared to the control group, reaching 6.39 (6.25; 6.42) nmol/mL (р1<0.001, р2<0.01, р3<0.05). Additionally, with the progression of the disease, a gradual increase in MA levels up to 6.39 (6.25; 6.42) nmol/mL, 7.88 (7.62; 7.92) nmol/mL, and 8.11 (8.05; 8.15) nmol/mL, respectively, was noted (р1<0.001, р2<0.01, р3<0.05), with a normal range of 3.14 (2.58; 3.17) nmol/mL. Similar trend was observed in serum CD levels - 3.11 (3.02; 3.18) IU, 3.69 (3.52; 3.72) IU, and 4.69 (4.53; 4.82) IU, respectively, with a normal range of 1.41 (1.32; 1.46) IU (р1<0.01, р2<0.01, р3<0.01). The study of LPO intensity via the optical density of aldehyde and ketone derivatives of neutral and basic dinitrophenylhydrazones (POM 356, POM 370, POM 430, POM 530) revealed an increase in POM product levels with the disease progression compared to the control group (р1<0.001, р2<0.01, р3<0.01). The analysis of the ADS showed an opposite trend, characterized by a significant decrease in marker levels. In patients with different ACO stages, serum CAT levels were 8.08 (7.95; 8.12) Н2О2/mL, 6.32 (6.25;6.41) Н2О2/mL, and 5.67 (5.59; 5.75) Н2О2/mL, respectively, with a normal range of 12.36 (12.21; 12.55) Н2О2/ml (р1<0.001, р2<0.01, р3<0.01), while SOD concentration decreased with the disease progression as well - 42.43 (31.75; 51.84) IU, 35.65 (24.72; 45.53) IU, and 32.18 (18.72; 41.15) IU, respectively, with a normal range of 63.60 (54.41; 74.56) IU (р1<0.001, р2<0.01, р3<0.01). In the compensated stage of ACO, CP level exceeded the normal value - 39.21 (38.92; 39.41) IU, with a normal range of 28.9 (28.4; 29.1) IU, indicating a compensatory defensive response of the body to a dramatic increase in LPO products. CP reserves, however, were depleted with the disease progression and a consistent decrease in this marker was subsequently observed: 19.10 (18.91; 19.23) IU in the subcompensated stage and 16.12 (16.01; 16.15) IU in the decompensated stage (р1<0.001, р2<0.01, р3<0.01).
 Conclusions. As a systemic process that induces various metabolic homeostasis disorders, endogenous intoxication serves as the pathogenetic foundation for the development of multiple organ failure in ACO patients. With ACO progression, endogenous intoxication caused an increase in LPO and POM activity, resulting in elevation of highly toxic middle-molecular weight substances, concurrently accompanied by a decline in the AOS activity.

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.

Peculiarities of changes in a functional condition of pro-oxidant and antioxidant systems in guinea pigs’ lungs in experimental allergic alveolitis under the conditions of immobilization stress

We have analyzed the results of investigation of alterations in indices of pro-oxidant (conjugated diene and malondialdehyde) and antioxidant (superoxide dismutase, ceruloplasmin, catalase) systems in guinea pigs’ lungs in experimental allergic alveolitis in the dynamics of EAA development under the conditions of immobilization stress. The investigation was conducted on 62 female guinea pigs weighing 180-220 g, divided into 4 groups: I – intact guinea pigs (n=20), II – guinea pigs (n=14) with EAA under the conditions of IS (1st day); III – guinea pigs (n=14) with EAA under the conditions of IS (2nd day); IV – guinea pigs (n=14) with EAA under the conditions of IS (34th day). The results of experimental investigation showed that a significant increase in conjugated diene level in animals’ lungs was observed at all stages of EAA development under the conditions of immobilization stress as compared with control group, indicating activation of this marker. The same changes occurred with MDA content, indicating excessive accumulation of this lipid peroxidation product in lung tissue. Intensive synthesis of free radical compounds caused activation of some components of enzymatic system of antioxidant defense. In particular, a moderate decrease in superoxide dismutase activity in lung tissue is observed in response to increased level of LOPs at early stages of EAA and immobilization stress development as compared with the indices in intact animals. The same situation is observed with catalase and ceruloplasmin activity in the lungs of guinea pigs with modeled AA and IS.

BIOCHEMICAL MARKERS OF MISCARRIAGE ASSOCIATED WITH THE INTRAPLACENTAL ACCUMULATION OF 137Cs.

to determine the biochemical markers of miscarriage associated with the accumulation of 137Cs in the placenta. According to the research design, pregnant women were divided into groups. Group 1included 153 women with reproductive losses in anamnesis and signs of termination of the current pregnancy.Group 2 (control) included 30 women with an uncomplicated pregnancy and medical history. The women of Group1 were divided into subgroups: 1a - in which the pregnancy ended with timely delivery, despite threatening signsof termination; 1b - pregnancy ended in late premature birth; 1c - pregnancy ended in early premature birth.Accumulation of 137Cs with different activity was detected in the placentas of both groups by β-spectrometry. Theeffect of 137Cs is the activation of free radical processes. The strength of oxidative stress was studied by the contentof diene conjugates (DC) and malondialdehyde (MDA) in the blood. The antioxidant capacity was determined by theactivity of catalase, glutathione-S-transferase, and superoxide dismutase (SOD). Biochemical studies were performed using a spectrophotometer «Specol-11» (Germany). The increase of DC in the 1st trimester by 2.25 times, in the 2nd and 3rd trimesters by 1.25 and 1.5 times indicates the activation of free radical reactions. The trigger for late preterm births is an increase in MDA in the 1sttrimester by 17.4 %. An increase in MDA by 23.4 % in the 1st trimester indicates the risk of early premature birth andintrauterine death of the fetus. A decrease in the activity of SOD in the 1st trimester by 13.0 % can be a predictor ofpremature birth. Decreased activity of SOD by 18.2 % in the 1st trimester indicates decompensation of adaptationmechanisms. As a result of oxidative stress caused by the accumulation of 137Cs in the placenta, the activity of GSTdecreases almost 2 times. In the 1st trimester, catalase activity in the blood of pregnant women of the 1b and 1csubgroups was reduced by 39.2 % and 44.9 %. The dynamics of catalase in the 2nd trimester indicate the activationof adaptive reactions. After 25 weeks, catalase activity is inhibited in pregnant women of subgroups 1b and 1c dueto depletion of antioxidant protection mechanisms. The activity of 137Cs in the placenta above 4.5 Bq/kg causesdepletion of antioxidant mechanisms, which is confirmed by persistent inhibition of catalase and SOD activityagainst the background of high levels of DC and MDA in the blood. Critical for pregnancy is the activity of 137Cs inthe placenta above 10.4 Bq/kg. The accumulation of 137Cs in the placenta leads to the activation of lipid peroxidation beyond thecapacity of the antioxidant system. Extreme effects depend on the 137Cs activity and placenta compensatory ability.Indicators of MDA, DC, SOD, and catalase are prognostic regarding the power of oxidative stress and pregnancyscenarios.

Long-term consequences of acute toxic prenatal hypoxia induced by sodium nitrite in rat experiments

Introduction. Gestational hypoxia plays an important role in fetal development, as it causes the development of oxidative stress and delayed psychomotor development. The aim of the study was to evaluate the prenatal effect of sodium nitrite on indices characterizing orienting and exploratory activity, mental activity and the degree of hypoxia in rat offspring. Materials and methods. Acute hypoxia was modeled by administration of sodium nitrite at a dose of 30 mg/kg intramuscularly to five pregnant rats during 16–19 days of gestation. Five females constituted a control group. In 50 born rats, orientation and exploration activity, cognitive functions, intensity of lipid peroxidation and glycolysis were studied. Results. The offspring of females that underwent acute hypoxia significantly lagged behind in the positive dynamics of body weight gain compared to control individuals. Thirty-day-old rats showed a pronounced disorder of the structure of behavioral pattern, learning process and long-term memory, increased content of diene conjugates, malonic dialdehyde and the level of lactate dehydrogenase activity in blood. Discussion. It was found that offspring whose mothers suffered acute hypoxia of toxic genesis developed pronounced behavioral disorders of psychomotor agitation and cognitive dysfunction characterized by decreased learning ability and impaired long-term memory. The content of primary and secondary products of lipid peroxidation and lactate dehydrogenase was increased in rats. The development of cellular oxidative stress under conditions of intrauterine hypoxia leads to oxygen deficiency in the fetus and a switch from tissue respiration to glycolysis, which underlies CNS damage. Conclusion. It was shown that sodium nitrite administration during the period from the 16th to the 19th day of gestation caused hyperactivity, depressed emotional status, and decreased orienting and exploratory activity and the ability to learn and retain a memory trace in rat offspring. Increased levels of diene conjugates and malonic dialdehyde, lactate dehydrogenase activity were observed in rats.

PROCESSES OF FREE RADICAL OXIDATION IN THERAPY FOR PATIENTS WITH ODONTOGENIC PHLEGMONS IN MAXILLO-FACIAL AREA IN THE PRESENCE OF ISCHEMIC HEART DISEASE

A large cohort of scientists is dealing with the issue of improving the treatment of maxillofacial odontogenic phlegmons. The course of these diseases is impacted by a significant number of factors, one of which is ishemic heart disease. Quercetin is a powerful antioxidant with a pronounced antioxidant effect. The use of 2-ethyl-6-methyl-3-hydroxypyridine succinate leads to increased oxidation of components, that is, to a synergistic antioxidant effect.
 The purpose of this study is to enhance the therapy of odontogenic phlegmons of maxillofacial area in patients with ishemic heart disease through the combined use of drugs with antioxidant, antihypoxant and angioprotective effects.
 Materials and methods. 80 patients with odontogenic phlegmon of maxillofacial area were examined. The participants were categorized into the following groups: Group 1 received parenteral quercetin, Group 2 received a combination of quercetin and intravenous administration of 2-ethyl-6-methyl-3-hydroxypyridine succinate, Group 3 received standard treatment (20 individuals), and Group 4 (control) comprised individuals without concomitant pathology who received the treatment according to a standard protocol (20 patients). To analyze the state of free radical oxidation processes in blood serum, the content of diene conjugates was studied.
 Results. The level of diene conjugates was increased when compared to the control group by 93.2%, 95.0% and 96.2% for the 1st, 2nd and 3rd clinical groups, respectively. On the third day of observation, patients with coronary heart disease displayed an increase in the studied indicator by 99.1%, 100.6%, and 97.8%, respectively, compared to the controls. After 5 days, in all four clinical groups, there was a decrease in diene conjugates content in blood serum compared to the previous observation period by 6.9%, 8.2%, 5.3% and 11.8%, respectively. A tendency to a gradual decrease in the content of diene conjugates was observed on the 7th day of observation in all groups by 5.5%, 6.8%, 4.2% and 11.8%, respectively, with its increase relative to the control by 112.9 %, 108.7% and 118.2% for the 1st, 2nd and 3rd clinical groups, respectively. On the 9th day of observation, a decrease in DC content by 2.7% was found only in patients of the 2nd clinical group. At the final follow-up period, a decrease in this marker was noted in all studied clinical groups relative to the previous follow-up period by 5.1%, 6.9%, 2.3%, and 9.7%, respectively.
 Conclusion: Under the combined administration of quercetin and 2-ethyl-6-methyl-3-hydroxypyridine succinate alongside a standard treatment protocol, the reduction in the level of diene conjugates in blood serum was most significant among patients with coronary heart disease, particularly in the later stages following surgical treatment.

Indicators of free radical oxidation in neutrophils of patients with primary and recurrent soft tissue sarcomas

Purpose of the study. To carry out a comparative analysis of lipid peroxidation intensity and antioxidant system indices in blood neutrophils of patients with primary and relapsed soft tissue sarcomas (STS) depending on sex and age.Patients and methods. Of the 81 patients included in the study, 48 had primary STS, 5 patients with continued growth, and 28 patients with recurrent STS. The patients were divided by sex and age; the level of lipid peroxidation products, superoxide dismutase (SOD) activity, total peroxidase activity (TPA), glutathione peroxidase (GPx) activity and reduced glutathione (RG) content in blood neutrophils were investigated by conventional spectrophotometric methods. The comparison groups (donors) consisted of 12 men and 17 women divided into the same age subgroups: ≤ 45 years and > 45 years.Results. In donors, there was a multiple decrease in the SOD/TPA ratio with age, especially in women, and in men this was accompanied by an age-related decrease in GPx activity. In primary sarcomas in older women and in men with continued growth and recurrence, there was an increase in diene conjugates (DC). In men over 45 years of age, there was an increase in SOD, TPA, and GPx. Women of the older age group were characterized by activation of SOD and GPx, expressed in the relapsed process to a significantly greater extent than in men, and an increase in RG was observed in women. The increase in both components of the glutathione system and SOD activity was especially significant in the development of relapses in women for periods exceeding three years, which was accompanied by a decrease in DC content. Conclusions. Neutrophils are characterized by an increase in DC content in patients of both sexes in the older age group with primary and recurrent STS, with its highest content in men with continued growth and relapses. GPx activity, increased in both men and women in the older age group in all variants of STS development, may play an important role in the antioxidant protection of blood cells in STS. Thus, the most pronounced activation of GPx, accompanied by a maximum increase in reduced glutathione and activation of SOD, contributes to a decrease in the level of DC and the absence of MDA increase in women with slow development of recurrences.

Metabolic accompaniment of plasma lipoproteins profile in persons with maladaptation

Background. During the implementation of the project "The relationship between the lipoprotein profile of the blood plasma and the parameters of the neuroendocrine-immune complex, and the influence of the factors of the Truskavets’ spa on them", we first divided observed cohort into 5 homogeneous groups that differed from each other by 6 discriminant variables. The purpose of this study is to identify the metabolic accompaniment of plasma lipoprotein profile in the same persons.
 Material and research methods. The object of observation were 41 volunteers: 20 women aged 30-76 years and 21 men aged 24-69 years without clinical diagnose but with dysfunction of neuroendocrine-immune complex and dysmetabolism. We estimated lipoprotein profile of plasma, determined the levels of the proinflammatory cytokines, parameters of lipid peroxidation as well as routine biochemical and paraclinical parameters.
 Results. The patients with increased, normal and decreased levels of Dobiásová’s&Frohlich’s Atherogenic Index of Plasma (D&FAIP) are characterized, together with levels of Triglycerides and HDLP Cholesterol by definition, by specific constellations of levels of IL-6, IL-1, Diene conjugates, Malondialdehyde, Katalase, Glucose, and Alanine aminotransferase (classification accuracy is 98.8%). A close canonical correlation was found between the parameters of the plasma lipoprotein profile, on the one hand, and metabolism and erythroon, on the other (R=0.920).
 Conclusion. Atherogenic, normal and anti-atherogenic blood plasma is characterized by specific levels of markers of inflammation, lipid peroxidation, cytolysis and erythroon.

Preclinical evaluation of a gel composition based on a flavonoid complex for the treatment of periodontal diseases in orthodontic patients

The aim of the work was a preclinical assessment of acute toxicity, skin resorptive, irritant effects, cumulative and catalase activity, as well as sensitizing properties of the local gel composition “Benzidaflaziverdine” (GCB) used for the treatment of periodontal diseases in orthodontic patients. Materials and methods. 119 animals were involved in the experiment, assigned to seven main and two control groups. GCB was administered intragastrically in doses of 300–600 mg/kg and intradermally of 200 μg into the outer surface of the ear. The native solution of GCB was applied to the skin and mucous membranes, administered orally by the method of “subchronic toxicity” and to the surface of the chorioallantoic membrane (CAM) of chicken embryos. The intensity of lipid peroxidation (LPO) was assessed by the level of diene conjugates (DCs) and malondialdehyde (MDA), and the antioxidant system by catalase activity. The specific leukocyte agglomeration reaction (SLAR), the specific leukocyte lysis reaction, and neutrophil damage indicators were used. Results. The median lethal dose LD50 for rats and mice of both sexes exceeded 5000 mg/kg. The irritant effect of GCB on the mucous membranes was manifested by hyperemia on the second day. Symptoms of irritation disappeared after 3–4 days without medical intervention. An analysis of the CAM blood vessels after exposure to GCB in two observations at the 120th second showed the beginning of hemorrhages. In one observation, GCB caused minor hemorrhages at the 300th second of the experiment. It was found that the coefficient of GCB irritant action was 5 (the mean score of Me (Q1; Q3) was 5 (4; 5)). The coefficient of cumulation (Kcum) exceeded 8.2. An insignificant increase in the median or mean values of catalase enzyme activity, DCs, and the amount of LPO end product such as MDA was observed compared to the control group animals. The SLAR test indicated the development of a delayed-type allergic reaction under the influence of GCB in a 1:10 dilution. One-hundred-fold dilution did not cause significant changes in the indicator in the main group compared to the control one. Conclusions. GCB belongs to the 4th class of toxicity – practically non-toxic substances, does not have sex- and species sensitivity, has weak cumulative activity, minimal effect on the system of LPO. GCB can be recommended for the use in clinical periodontology for medical support of orthodontic patients.

Rehabilitation of children with Lyme arthritis

Background. Lyme disease is a common tick-borne infection. Untimely diagnosis and treatment lead to the chronicity of the process with the development of late lesions of various systems and organs and possible disability. The purpose of the study was to develop a program of rehabilitation measures for children with Lyme disease. Material and methods. The research was conducted on the basis of the Ternopil Regional Children’s Hospital. Twenty children, residents of the Ternopil region, who applied to the Ternopil Regio­nal Children’s Hospital for tick bites and, as a result, diagnosed Lyme arthritis, took part in the study. To assess the severity of pain, we used scales and questionnaires for the diagnosis of DN4 neuropathic pain. Laboratory and instrumental studies were performed such as evaluation of the level of malondialdehyde, diene conjugates, superoxide dismutase. Results. Clinical examination of tick-affected children with Lyme disease showed that the most common primary clinical manifestation is a typical skin lesion — erythema migrans. In case of arthritis, all children notice inflammatory changes and pain in the joints. As a result of the conducted studies, the activation of peroxidation in children with Lyme disease was detected (an increase in the level of malondialdehyde and a decrease in superoxide dismutase, diene conjugates). It was shown that combined therapy with the use of magnetic laser therapy leads to the normalization of lipid peroxidation. Conclusions. All children with Lyme arthritis have a pain syndrome of varying severity. In patients with Lyme disease, there is an increase in the activity of lipid peroxidation and a decrease in the functional capacity of the antioxidant defense system. Children who underwent traditional treatment for Lyme arthritis reported a partial normalization of lipid peroxidation as evidenced by a significantly decreased level of diene conjugates compared to controls. In the group of patients who underwent combined treatment for Lyme arthritis (antibacterial therapy + magnetic laser therapy), the activity of antioxidant defense was normalized. Combination of magnetic laser therapy with antibacterial therapy demonstrates an improvement of pain status and faster rehabilitation of children.