Final Products Of Lipid Peroxidation Research Articles

INTENSITY OF OXIDATIVE STRESS AS A UNIVERSAL MECHANISM OF TISSUE DAMAGE IN NONALCOHOLIC STEATOHEPATITIS AND DIABETIC KIDNEY DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS. QUERCETIN CORRECTION EFFECTIVENESS

The objective of the research was to determine the intensity of the effect of a complex of Metformin, Rosuvastatin, Essentiale Forte N and Quercetin on the state of oxidative-antioxidant homeostasis, as well as the intensity of hepatocyte apoptosis by cytokeratin-18 in the blood that are the factors in the progression of nonalcoholic steatohepatitis and diabetic kidney disease. Material and methods. 75 patients with non-alcoholic steatohepatitis with type 2 diabetes mellitus and stage I­–III diabetic kidney disease were studied over time. According to the prescribed treatment, the examined patients were divided into 2 groups: (group 1 ­– the controls: 37 patients) received a low-calorie diet with dietary restrictions No.9, essential phospholipids (Essentiale forte H 300 mg 2 caps. 3 times a day) for 30 days for the treatment of active non-alcoholic steatohepatitis, Metformin Hydrochloride (Metformin-Teva) 1000 mg per day, Rosuvastatin (Rosuvastatin-Teva 5 mg once daily) for 1 month for concomitant type 2 diabetes mellitus and hyperlipidemia. Group 2 consisted of patients (38 people) who in addition to similar dietary recommendations and therapy received additionally Quercetin and Povidone (Corvitin) 500 mg intravenously per 100 ml of isotonic chloride for 10 days. Results. It was found that the comorbid course of nonalcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus is accompanied by a significant increase in the intensity of oxidative stress, accompanied by an increase in blood intermediate and final products of lipid peroxidation. The damaging effect of oxidative stress in patients with type 2 diabetes mellitus leads to the activation of apoptosis of hepatocytes with an increase in blood cytokeratin-18 (7.5 times, p < 0.05), the content of which correlates with the degree of oxidative stress, the intensity of liver damage and stage of diabetic kidney disease (p < 0.05). Oxidative stress increases the risk of endothelial damage by atherosclerotic process due to hyperproduction of homocysteine (3.9 times, p < 0.05), which contributes to the progression of diabetic kidney disease. The use of Quercetin in the complex therapy of non-alcoholic steatohepatitis and type 2 diabetes mellitus with diabetic kidney disease contributes to the reduction of oxidative stress, increased activity of antioxidant defense factors (content of reduced glutathione in erythrocytes, reduction of cytokeratin-18 content by 1.7 times) and endothelial damage (reduction of homocysteine content in blood by 1.9 times) (p < 0.05). Conclusions. The comorbid course of nonalcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus is accompanied by a significant increase in the intensity of oxidative stress, and in the content of intermediate and final products of lipid peroxidation and oxidative modification of proteins (p < 0.05).

The intensity of the processes of lipid peroxidation in the blood of cows in experimental fasciolosis

Among the most common pathologies of parasitic etiology in ruminants, trematode diseases, namely fasciolosis, occupy a prominent place in terms of the degree of damage and economic damage caused. Activation of lipid peroxidation processes plays a significant role in the mechanisms of the development of fasciolosis in animals. The research aimed to investigate the level of lipid peroxidation products in cows' blood in experimental fasciolosis. For the test, 12 cows of 4–5 years of age, black-spotted breed, were selected, from which 2 groups were formed, six animals in each. Animals in the control group were clinically healthy. Animals of the experimental group were experimentally infected with adolescents. During the research, the rules of compulsory experiments were followed – selecting and keeping analog animals in groups. The cows' diet was balanced in terms of nutrients and minerals. Based on the studies, it was found that after the experimental infestation of cows of the experimental group with the causative agent of fasciolosis, an increase in the level of diene conjugates of their blood on the 15th day of the experiment by 30.3 %, and on the 25th day – by 50.4 % relative to the control group. There was also an increased level of lipid hydroperoxides in their blood, where, respectively, on the 10th and 15th day of the experiment, this figure increased by 18.3 and 32.9 % compared with the control group. On the 25th day of the experiment, the level of lipid hydroperoxides in the blood of cows of the experimental group was the highest. Compared with the control group, it increased by 46.6%, respectively. In the study of the final products of lipid peroxidation, it was found that on the 10th day of the test, the level of TBA-active products in infected cows of the experimental group increased by 9.5 %. On the 15th and 20th days of the experiment, the level of end products of LPO in the experimental group's blood of animals was higher by 20.3 and 26.0 % relative to the control group. The increase in TBA-active products' level reflects the activation of peroxide processes in animals with experimental fasciolosis. Therefore, in the clinical manifestation of fasciolosis, parasites secrete metabolic products that promote the formation of free radicals, which in turn enhance the initiation of lipid peroxidation processes.

REDUCTION OF OXIDATIVE STRESS OF PULMONARY MEMBRANES DURING LYMPHOTROPIC ADMINISTRATION OF ISONIAZID

The article presents the results of a clinical study of the severity of oxidative stress in the treatment with isoniazid on the material of bronchoalveolar flushes. The object of the study was patients with infiltrative pulmonary tuberculosis who had their bronchoalveolar lavage (BAS) removed during FBS. 19 patients received lymphotropic administration of isoniazid (group 1), 21 patients received intramuscular injection of isoniazid by needle-jet method (group 2), 20 patients were in the 3rd control group with traditional intramuscular administration of isoniazid as part of standard 4 ABP regimens. Lymphotropic injections were performed sequentially in the area of the jugular fossa, behind the xiphoid process, and in the parasternal zone. Group 2 patients were injected with a 10% isoniazid solution in an amount of 1.0 ml into the intercostal space in the projection of the inflammatory focus using a semi-automatic combined ISI-1 acupuncture injector. The content of total protein, malondialdehyde (the final product of lipid peroxidation) and isonicotinic acid hydrazide (non-metabolized GINK, which is part of the anti-tuberculosis drug isoniaziada) was studied in BAS using biochemical methods. Total protein and MDA in patients with tuberculosis are at a high level, reflect the intensity of inflammation and decrease with lymphotropic and intra-pulmonary administration of isoniazid. The content of GINK in BAS is higher with its lymphotropic administration. Based on the study of these tests and the content of GINK in bronchoalveolar flushes, it can be argued that local and regional lymphotropic administration of isoniazid has a greater anti-inflammatory effect on the membranes of the lungs and tracheobronchial tree than intramuscular administration.

HYPERURICEMIA AS A MARKER OF LIPID PEROXIDATION INTENSITY IN A POPULATION

The prevalence of hyperuricemia in the world has been steadily increasing over the past decade. According to various authors, the frequency of asymptomatic hyperuricemia in the population ranges from 5 to 35.1 per cent. The study of the relationship between purine metabolism disorders and the state of lipid peroxidation is still relevant due to numerous reports on the relationship between the processes of urate formation and free radical oxidation. Therefore, the aim of the study was to find out the value of hyperuricemia as a marker of the intensity of lipid peroxidation in a random population sample. Materials and methods. The group of participants was formed according to generally accepted epidemiological approaches using a random sample of workers and employees of an industrial enterprise (n=727 people, 457 men and 270 women, age ranged from 18 to 65 years, the average age was 38.13±5.10 years. Metabolic syndrome was diagnosed according to the recommendations of International Diabetes Federation, National Heart, Lung and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, and International Association for the Study of Obesity. Glucose homeostasis was evaluated according to the recommendations of the research society for the study of diabetes in India, Endocrine Society of India, 2020. Venous blood samples were taken on an empty stomach. We assessed the immunoreactive insulin content by immunochemiluminescent method, the concentration of triglycerides, cholesterol, high density lipoprotein by enzyme colorimetric method, xanthine and hypoxanthine were assessed by the method of S. V. Oreshnikov et al., uric acid was evaluated by colorimetric method, acylhydrazines – by the method of V. B. Gavrilov and M. I. Mishkorudny, malonic dialdehyde was assessed by the method of I. D. Steel, Garishvili T. G. in modification of L. I. Andreeva et al.; the level of total reduced SH groups was evaluated by the Elman photometric method, xanthine oxidase activity was studied by the photometric method, superoxide dismutase was examined by the T. V. Sirota method, and catalase in plasma and red blood cells – by the H. Aebi method. Results and discussion.
 Hyperuricemia was diagnosed in 118 (16.2%) patients. Violation of glucose homeostasis was diagnosed in 76 patients (10.5%): type 2 diabetes was found in 22 (3.03%) patients, glucose tolerance disorders were found in 47 (6.5%) patients, fasting hyperglycemia – in 7 (0, 96%), respectively. In a random population sample with hyperuricemia, the concentration of intermediate and final products of lipid peroxidation in the blood is significantly higher than in individuals with normouricemia. The concentration of reducing equivalents in the form of free SH groups does not significantly depend on the intensity of purine catabolism. The maximum intensity of lipid peroxidation is observed in the representatives of a random population sample with hyperuricemia in the presence of impaired glucose homeostasis. For this combination of pathological conditions, the concentrations of intermediate and final products of lipid peroxidation are significantly higher than for hyperuricemia by itself and hyperuricemia in combination with other components of the metabolic syndrome. The established links between disorders of purine metabolism and activation of lipid peroxidation demonstrate a close integration of purine metabolism pathology into hormonal and metabolic disorders of diabetogenic and atherogenic orientation at the level of a random population sample.

Динамика показателей перекисного окисления липидов в толстом кишечнике при экспериментальной болезни Крона в условиях применения ректальных суппозиториев с экстрактом корневищ куркумы длинной

Цель исследования - проведение сравнительного анализа влияния экстракта куркумы длинной и 5-аминосалициловой кислоты (5-АСК) в составе ректальных суппозиториев на клиническую картину и содержание продуктов перекисного окисления липидов (ПОЛ) в слизистой оболочке толстого кишечника при экспериментальной болезни Крона (БК). Методика. Эксперимент выполнен на 70 белых крысах-самцах Wistar. БК моделировали ректальным введением тринитробензосульфоновой кислоты. Ректальные суппозитории (массой 0,3 г каждая) начинали применять через 12 ч. Содержание 5-АСК в суппозиториях составляло 50 мг, 10% экстракта куркумы длинной оригинального состава 0,000075 г. На 3-и, 5-е и 7-е сут после моделирования БК оценивали клинический статус по модифицированной шкале Disease activity index и содержание продуктов ПОЛ в слизистой оболочке толстого кишечника. Результаты. В динамике БК в толстом кишечнике увеличивается содержание первичных, вторичных и конечных продуктов ПОЛ в гептановой и изопропанольной фазах; тяжесть клинических признаков (снижение массы тела, диарея, кровь в каловых массах) нарастает по мере увеличения содержания продуктов ПОЛ. Применение при БК ректальных суппозиториев с экстрактом куркумы снижает выраженность клинических симптомов, уменьшает содержание продуктов ПОЛ преимущественно в изопропанольной фазе липидного экстракта толстого кишечника; установлена корреляция индекса клинической активности БК с содержанием продуктов ПОЛ в толстом кишечнике. Заключение. Эффективность локального применения экстракта куркумы в составе ректальных суппозиториев сопоставима по эффективности с применением ректальных суппозиториев с 5-АСК по показателям индекса клинической активности и по содержанию продуктов ПОЛ в слизистой толстого кишечника. Aim. To compare effects of turmeric extract and 5-aminosalicylic acid (5-ASA) formulated into rectal suppositories on clinical symptoms and content of lipid peroxidation products (LPP) in the mucous membrane of the large intestine in experimental Crohn’s disease (CD). Methods: Experiments were performed on 70 Wistar male rats. CD was modeled by rectal administration of trinitrobenzenesulfonic acid; rectal suppositories (0.3 g each) were used every 12 h. The suppositories contained 5-ASA (50 mg) or 10% turmeric extract with an original composition (0.000075 g). On days 3, 5, and 7 of CD, the clinical status was evaluated with a modified Disease Activity Index scale, and LPP concentrations were measured in the large intestine mucosa. Results. In the course of CD in the colon, concentrations of primary, secondary, and final LPP in the heptane and isopropanol phases increased; severity of clinical signs (weight loss, diarrhea, blood in fecal masses) increased with increasing LPP concentrations. The use of rectal suppositories with turmeric extract alleviated severity of clinical symptoms and reduced LPP content primarily in the isopropanol phase of colon lipid extract. The index of CD clinical activity of CD was correlated with the large intestinal LPP content. Conclusion. Effectiveness of the local application of turmeric extract formulated into rectal suppositories was comparable with that of rectal suppositories with 5-ASA as determined by the Disease Activity Index and the LPP content in the large intestine.

Expression of inflammatory factors and oxidative stress markers in serum of patients with coronary heart disease and correlation with coronary artery calcium score

Expression characteristics of inflammatory factors interleukin-23 and interleukin-35; oxidative stress markers of malondialdehyde, which is a final product of lipid peroxidation; superoxide dismutase; microRNA-126 and microRNA-146a in serum of patients with coronary heart disease were investigated. Correlation between these biomarkers and CACS (calcification score), as well as the underlying clinical significance were evaluated. A total of 192 patients diagnosed with coronary heart disease were recruited as the observation group, and 69 healthy adults who provided their blood samples were selected as the control group. Enzyme linked immunosorbent assay was carried out to measure the levels of inflammatory factors interleukin-23 and interleukin-35, and the levels of oxidative stress markers of malondialdehyde and superoxide dismutase in serum of the patients and healthy subjects. Real-time fluorescence-based quantitative PCR was performed to measure the expression levels of microRNA-126 and microRNA-146a in serum. The differences in expression of these biomarkers were analyzed, and correlation between these biomarkers and coronary artery calcium score were assessed. The differences in expression levels of interleukin-23, interleukin-35, malondialdehyde, superoxide dismutase, microRNA-126 and microRNA-146a were statistically significant in both groups. The expression levels of interleukin-23, interleukin-35, malondialdehyde, superoxide dismutase, microRNA-126 and microRNA-146a in the observation group were closely associated with severity of the disease. There were positive correlations between coronary artery calcium score and interleukin-23, interleukin-35, malondialdehyde, microRNA-126 and microRNA-146a, respectively; while a negative correlation existed between coronary artery calcium score and superoxide dismutase in the observation group. In conclusion, biomarkers interleukin-23, interleukin-35, malondialdehyde, superoxide dismutase, microRNA-126 and microRNA-146a were abnormally expressed in serum of patients with coronary heart disease, implicating their association with onset and progression of the disease. The biomarkers were found to be correlated with coronary artery calcium score. Detection of changes of related biomarkers in serum may have certain value in diagnosis of disease formation, as well as assessment of disease severity.

Effectivness of antral on oxidant-antioxidant homeostasis in patients with chronic pancreatitis

Objective – to establish the effectiveness of Antral in the treatment of exacerbation phase of chronic pancreatitis (CP) based on a comprehensive assessment of the clinical course of CP and oxidative-antioxidant homeostasis.Material and methods. 52 patients with CP of mixed etiology in the moderate severity exacerbation phase were examined. To represent the effectiveness of treatment on a random basis, two representative groups of patients were formed. The average age of patients was (41.3±4.5) years. The design of the research included clinical, laboratory, biochemical blood tests, enzyme immunoassay, biochemical analysis of duodenal contents, coprogram, ultrasonography (USG) of the pancreas. Analysis of clinical, USG manifestations of CP, biochemical, laboratory indicators of the functional state of the pancreas was performed according to conventional methods, which were studied in the dynamics after 30 days of treatment.Results. Before treatment, a significant intensity of oxidative stress with an increase in the content of intermediate and final products of lipid peroxidation (1.6-1.7 times, p<0.05), oxidative protein modification (2.3 times), p<0.05), induction of nitrosative stress (1.5 times, p<0.05), which arose against the background of a significant deficiency of reduced glutathione in the blood (1.3 times, p<0.05) and were accompanied by a compensatory increase of catalase activity (by 1.5 times, p<0,05) detected in patients with CP. The prescription of Antral on the background of complex therapy of exacerbation of CP for 30 days led to a significant correction of oxidative-antioxidant homeostasis in patients with CP with a significant decrease in blood malonic aldehyde (1.3 times, p<0.05), isolated double bonds (1.5 times, p<0.05), the alkaline aldehyde and ketondinitrophenylhydrazones (1.8 times, p<0.05), nitrites/nitrates (1.5 times, p<0.05) due to the significant increase and normalization of the content of reduced glutathione in erythrocytes (1.3 times, p <0.05), normalization of catalase activity, accompanied by probable elimination of clinical manifestations of exacerbation of CP: astheno-vegetative syndrome (OR=3.18, 95% CI) 1.18- 8.63), pain in the left hypochondrium (OR=2.67, 95% CI 1.05-6.75), stomach bloating (OR=3.06, 95% CI 1.13-8, 32) (p<0,05), elimination of inflammatory edema of the pancreas (OR=2,67, 95% CI 1,05-6,75), hyperenzymaemia syndrome, inflammatory syndrome (OR=3,22, 95% CI 1), 22-8,94) and increase of exocrine function of the pancreas (OR=3,77, 95% D and 1.24-11.49) (p<0.05).Conclusions. The proposed complex therapy, with the addition of Antral, demonstrated a higher degree of effectiveness, compared with the basic therapy, in achieving the antioxidant effect, which allowed reducing the intensity of lipid peroxidation and protein oxidative modification, nitrosative stress, which are the main elements in the pathogenesis of exacerbation of chronic pancreatitis.

INTENSITY OF LIPID PEROXIDAL OXIDATION PROCESSES IN RATS' BLOOD AT CONTINUOUS CADMIUM AND LEAD LOAD

Lead and Cadmium are attributed to thiol poisons due to their ability to bind to SH groups of proteins. The aim of the study was to study the effect of Cadmium and Lead salts on the intensity of lipid peroxidation processes in the blood of rats. The experiments were performed on male rats of the Wistar line, weighing 200–220 g, from which 4 groups of animals were formed: control and 3 experimental groups. Control rats were administered drinking water through a metal probe in a volume equivalent to the volume of aqueous solution of Cd2 + and Pb2 + salts. The animals of the first experimental group were administered a 0.029% aqueous solution of cadmium chloride at a dose of 4.0 mg / kg. Animals of the second experimental group were administered a 16.6% aqueous solution of lead acetate at a dose of 200 mg / kg. Animals of the third experimental group were administered 16.6% aqueous lead acetate solution at a dose of 100 mg / kg and 0.029% aqueous cadmium chloride solution at a dose of 2.0 mg / kg.
 The administration of cadmium chloride and lead acetate to the body leads to the accumulation in the blood of rats of the experimental groups of both intermediate and final products of lipid peroxidation. A significant increase in the level of lipid peroxidation products was observed in the blood of rats of all three study groups from the first day of the experiment. With cadmium and lead combined, rats were found to have the highest levels of diene conjugates and TBA-active products compared to the first and second experimental groups. On the 28th day of the experiment, the level of lipid peroxidation oxidation products in the blood of rats of the third experimental group increased by 76.1%, and the level of TBA-active products - by 38.4% relative to the control group. These changes in the level of lipid peroxidation products indicate an increase in the intensity of radical formation processes. Peroxide oxidation forms, at almost all stages of its course, a number of products that result from the interaction of free radicals with each other and with biological macromolecules.
 The investigations made it possible to reveal the pathogenesis of Cadmium and Lead toxic effects on the rat organism more deeply and to use these data in the development of antidote for cadmium-lead intoxication.

ШЎРЛАНИШ ШАРОИТИДА ҒЎЗАНИНГ ОКСИДЛАНИШ ЖАРАЁНЛАРИГА ДАГ-1 ВА ДАГ-2 ТАБИИЙ АСОСЛИ ПРЕПАРАТЛАРИНИНГ ТАЪСИРИ

Salt stress enhances the formation of reactive oxygen species in plant tissues associated with damage to the structure of cell macromolecules, leading to disruption of cellular metabolism. The use of drugs of natural origin DAG-1 and DAG-2 can be effective in adapting cotton to the effects of salts. The activity of the pro-/antioxidant system in 7-day-old cotton seedlings, seeds of which were treated with DAG-1 and DAG-2 drugs and germinated in various concentrations of NaCl solution (100 mM, 200 mM, 300 mM) has been studied. Salinity resistance is manifested in cotton varieties treated with natural drugs DAG-1 and DAG-2, in which a high activity of the key enzyme of the antioxidant system - superoxide dismutase, low content of final product of lipid peroxidation – malondialdehyde and the accumulation of free proline amino acid with osmoprotective property have been identified.

Influence of “Thireomagnile” and “Thyrioton” preparations on the antioxidant status of pregnant cows with symptoms of endotoxicosis

The purpose of this search was to investigate the influence of “Thireomagnile” and “Thyrioton” on the antioxidant status of cows in the development of endotoxicosis. The experimental part of the work was performed at the Department of Pharmacology and Toxicology of Stepan Gzhytskyj Lviv National University of Veterinary Medicine and Biotechnologies, in the laboratory of Pharmacology and Toxicology of the State Scientific Research Institute of Veterinary Preparation and Feed Additives (Lviv) and in the Ltd. “Barkom”, village Yampil of Pustomyty district, Lviv region. To solve the tasks of the research, three experimental groups of 10 pregnant cows of the Ukrainian Black-Spotted Dairy breed were formed in each: control and two experimental. Cows of the control group (K) had characteristic clinical signs of endotoxicosis. Animals of the first experimental group (E1) were given 10 mL per animal of “Thyroid magnet” at the eighth and ninth months of gestation. The animals of the second experimental group (E2) were given Thyrioton at a dose of 10 mL per animal in the eighth and ninth months of gestation. As a result of the conducted researches it is found out that in pregnant cows with clinical manifestation of endotoxicosis the inhibition of the activity of the antioxidant protection system and intensification of processes of lipid peroxidation occurs. The use of “Thireomagnile” and “Thyrioton” in cows by the development of endotoxicosis contributed to the increased activity of the antioxidant system, which is indicated by an increase in the activity of glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase. The use of of “Thireomagnile” and “Thyrioton” to cows in the development of endotoxicosis contributed to the suppression of lipid peroxidation processes, which is indicated by the low level of primary and final products of lipid peroxidation, namely: lipid hydroperoxides and TBA-active products. Better normalizing action on the equilibrium on the activity of the antioxidant system and the intensity of lipid peroxidation was shown by the introduction of “Thyroid magnet” at a dose of 10 cm3 per animal.

Lipid peroxidation, antioxidant defense parameters, and dynamics of surgical treatment in men with mechanical jaundice of various origins

Mechanical jaundice is a severe pathological condition caused by obstruction of the bile duct, usually requiring surgical intervention. Mechanical jaundice occurs in 45–50% of all cases of jaundice of all types, and may be of either non-tumor or tumor origin. Due to involvement of oxidative stress reactions in mechanical jaundice pathogenesis, it is relevant to study the parameters of this process. This study assesses lipid peroxidation-antioxidant defense components in men with mechanical jaundice of non-tumor and tumor origin in the context of surgical treatment. This study examined 47 men with mechanical jaundice of non-tumor origin (MJNT) and 45 men with mechanical jaundice of tumor origin (MJT) (stages I-II of the tumor process). Data from 100 healthy men served as the control. High activity of lipid peroxidation accompanied by falling concentrations of antioxidant enzymes were observed in men with MJNT. Increased primary and final lipid peroxidation products and decreases in almost all studied components of the antioxidant defense system (superoxide dismutase, glutathioneS-transferase, glutathione peroxidase, and ceruloplasmin) were observed. Similar observations emerged for patients with MJT, but with greater changes in parameters. The only indicator of difference between the groups was ceruloplasmin, with lower values in the MJT group. The MJNT group showed decreased thiobarbituric acid reactant values, catalase and ceruloplasmin both values were increased post-surgery. The post-surgery MJT group showed decreased conjugated dienes values and increased catalase and ceruloplasmin values. Thus, in MJNT patients, changes in the lipid peroxidation system relate to the stage of final products, which may serve as a favorable sign, in contrast to the MJT group, where changes concern only the stage of primary products. Based on the data obtained, antioxidant drugs are advised for patients with mechanical jaundice, with special attention given to the tumor origin of the disease.

Активность окислительных процессов при эндометрите у крыс

Введение. Проблема лечения эндометрита связана в первую очередь с трудностями своевременной дифференциальной диагностики и отсутствием четких клинико-лабораторных критериев. Женщины с хроническим эндометритом в анамнезе даже при условии прегравидарной подготовки составляют группу высокого риска по развитию акушерских и перинатальных осложнений, причиной которых является внутриматочная инфекция. Возбудителями являются прежде всего микроорганизмы, поражающие цилиндрический эпителий канала шейки матки: гонококки и хламидии, мико- и уреаплазмы, которые снижают защитные свойства шеечной слизи, что облегчает распространение восходящей инфекции. Цель исследования -- поиск значимых лабораторных критериев диагностики эндометрита в эксперименте. Методика. Опыты проведены на крысах Wistar, массой 180-200 г. Эндометрит моделировали путем ретроградного введения взвеси аутокалла в полость матки с помощью спринцевания. Маркерами окислительных процессов в организме были выбраны показатели перекисного окисления липидов и окислительной модификации белков. Активность перекисного окисления липидов оценивали по содержанию в плазме крови диеновых и триеновых конъюгатов и оснований Шиффа. Уровень окислительной модификации белков изучали в реакции взаимодействия окисленных аминокислотных остатков белков плазмы с 2,4-динитро-фенилгидразином с образованием альдегид- и кетондинитрофенилгидразонов основного и нейтрального характера, которые регистрировали спектрофотометрически. Результаты. Показано, что у крыс с эндометритом возрастало количество инициальных и конечных продуктов перекисного окисления липидов. При оценке активности окислительной модификации белков в плазме крови показано повышение концентрация карбонильных производных окисленных белков нейтрального и основного характера. Заключение. Выявленный эффект может быть опосредован повышенным уровнем активных форм кислорода, образующихся при действии бактериальной флоры, а также защитной реакцией нейтрофилов, реагирующих на появление антигенных агентов. Можно полагать, что под воздействием продуктов перекисного окисления липидов и окислительной модификации белков происходит повреждение мембран клеток эндометрия, что может быть одной из причин расстройства репродукции, синдрома хронической тазовой боли и развития бесплодия. Данные могут быть использованы для объективизации критериев и ранней лабораторной диагностики эндометрита. The challenge of treating endometritis is associated primarily with the difficulty of timely differential diagnosis and the absence of distinct clinical and laboratory criteria. Women with a history of chronic endometritis, even with a pregravid preparation, constitute a high-risk group for the development of obstetric and perinatal complications caused by intrauterine infection. The pathogens are primarily microorganisms that affect the cylindrical epithelium of cervical canal, gonococci, chlamydia, myco- and ureaplasmas, which impair protective properties of the cervical mucus and facilitate the spread of ascending infection. The aim of the study was experimental searching for significant and reliable laboratory criteria for the diagnosis of endometritis. Methods. Experiments were performed on Wistar female rats weighing 180-200 g. Animals were divided into the groups of intact animals and experimental animals with endometritis induced by retrograde injection of auto feces suspension into the uterine cavity by douching. Markers of oxidative processes included products of lipid peroxidation (LP) (triene and diene conjugates and Schiff bases) and protein oxidation (protein carbonyls) in rat plasma. Results. Plasma concentrations of initial and final LP products as well as of neutral and basic carbonylated proteins were increased in rats with experimental endometritis. Conclusion. The observed effect of experimental endometritis was apparently due to increased production of reactive oxygen species by the bacterial flora administered into the rat uterine cavity. In addition, this effect could result from the protective response of neutrophils to antigenic agents. Apparently, both LP products and oxidation-modified proteins damage cell membranes including endometrial membranes, which may cause reproductive disorders, chronic pelvic pain, and infertility. In future, after clinical studies, these indexes could be used to enhance objective and early laboratory diagnosis of endometritis.

Фармако-математичний аналіз залежності «структура – активність» координаційних сполук германію за синдрому тривалого розчавлювання

Мета дослідження – провести комплексний порівняльний фармако-математичний аналіз ефективності координаційних сполук германію з біолігандами у посткомпресійному періоді на підставі результатів скринінгу потенційних засобів фармакотерапії наслідків синдрому тривалого розчавлювання (СТР). Експериментальною моделлю ендотоксикозу посттравматичного генезу був патологічний процес, який розвивався у тварин у результаті розчавлювання м’яких тканин задніх кінцівок протягом 5 год у спеціальному приладі з манометричним контролем тиску. Кількісними критеріями фармакотерапевтичної ефективності досліджуваних сполук в умовах ендотоксикозу на тлі СТР були концентрація кінцевих продуктів перекисного окиснення ліпідів (ПОЛ), що реагують з 2-тіобарбітуровою кислотою (ТБК-реактанти) у гомогенаті печінки щурів і рівень молекул середньої маси (МСМ) у сироватці крові щурів. Кореляційні залежності «структура – активність» проводили за методом найменших квадратів. За результатами скринінгової серії досліджень потенційних засобів фармакотерапії наслідків СТР проведений комплексний фармако-математичний аналіз активності координаційних сполук германію з біолігандами. Показано, що ефективна детоксикація організму за умов СТР притаманна сполукам германію з комплексним органічним аніоном – (Мігу-4-6,8,9). Максимальну здатність зменшувати вміст універсальних маркерів ендогенної інтоксикації проявила сполука (Мігу-6), у разі введення якої рівень МСМ знижується в 2 рази, а концентрація ТБК-реактантів знижується в 4,4 разу порівняно з контрольною групою. Показано, що між концентрацією ТБК-реактантів у гомогенаті печінки щурів і вмістом МСМ у сироватці крові щурів існує залежність, коефіцієнти кореляції (детермінації) якої змінюються в незначному ступені за порівняння різних груп без тіотриазоліну та таких, що містять і тіотриазолін, зокрема, коефіцієнт лінійної кореляції для групи А та групи А1 становить 0,986 і 0,908 відповідно. Отримані дані вказують на правильність вибору тіотриазоліну як препарату порівняння за умов екстремального стану, що вивчається, та можуть бути фармако-математичним обґрунтуванням доцільності його використання на етапі клінічних досліджень. Залежність показників МСМ і ТБК-реактантів від кількості акцепторів та донорів водневого зв'язку, дипольного моменту, енергій ван-дер-ваальсових та електростатичних взаємодій характеризується показниками – коефіцієнтами кореляції та детермінації (rxy, R2) різного рівня. Для показника МСМ найхарактернішим є зв'язок з акцепторами водневого зв'язку (rxy = 0,931, група С), тоді як для показника ТБК-реактантів зв'язок з акцепторами водневого зв'язку характеризується значенням rxy на рівні 0,481 (група С).

Anti-inflammatory and hemostatic effects of Linaria reflexa Desf

The work presented here was aimed to investigate the in vivo anti-inflammatory and in vitro hemostatic activities of Linaria reflexa extract and to establish the relationship between its bioactivity and chemical composition. Twenty-three secondary metabolites were identified, most of them are good anti-inflammatory agents, in line with data by carrageenin-induced rat paw edema assays of the n-butanol extract showing high anti-inflammatory inhibition (63.90%) of edema swelling in the rat paw at the dose 200 mg/kg after 4 h. Furthermore, both extent of inflammatory response and tissue injury were prevented keeping the levels of rate myeloperoxidase (60.16%) and of malondialdehyde, which is the final product of lipid peroxidation generated by free radicals (58.58%). The same extract showed also a remarkable hemostatic effect established by measuring the coagulation time of decalcified plasma (45 s), related to its flavonoid glycosides content.

THE INFLUENCE OF COMPLEX ANTIOXIDANT THERAPY ON THE DYNAMICS OF CHANGES OF OXIDANT STRESS INDICES IN THE BODY OF PREGNANT WOMEN WITH DIFFUSE TOXIC GOITER

Objective of the article is to study the effect of antioxidant therapy on the level of lipidsperoxidation products and antioxidant defense system in pregnant women with diffusetoxic goiter.Material and methods. The subject of the study was 65 pregnant women with diffusetoxic goiter of mild degree and 64 with moderate degree of severity, receiving thecommon therapy and combining the latter with the antioxidant one. The control group consisted of 30 women with physiological course of pregnancy. The initial and finalproducts of lipid peroxidation as well as enzymes of the defense antioxidant system inthe groups, were studied, depending on the received system of treatment.Results. While using the antioxidant therapy in the complex treatment of pregnantwomen with diffuse toxic goiter, the state of lipid peroxidation is likely to be normalizedin mild forms of thyrotoxicosis and with moderate degree - the tendency to levellingsimilar indicators in the group of pregnant women with a mild degree before treatmentis observedConclusions. The use of complex antioxidantal therapy is one of the pathogeneticprinciples of correction of fetoplacental insufficiency in pregnant women with diffusetoxic goiter.

Dynamics of changes in lipid peroxidation and antioxidant protection under the influence of complex treatment in patients with comorbid course of non-alcoholic steatohepatitis

O. Yu. Filippova The aim to assess the effect of various complex treatment regimens on lipid peroxidation (LPO) and antioxidant protection (AOP) in patients with non-alcoholic steatohepatitis (NASH) in combination with obesity (OB) and biliary tract pathology (BT), based on 6-month follow-up data. Materials and methods. We examined 100 patients with NASH in combination with OB and pathology of BT. The control group consisted of 30 practically healthy persons. Patients of all groups within 6 months have been prescribed a lifestyle correction, in particular: diet, exercise, work and rest. Patients of the 1 group (n = 34) received standard treatment for 30 days. Patients of the 2 group (n = 33) were prescribed standard treatment combined with the use of ursodeoxycholic acid (UDCA) for 30 days at a dose of 15 mg·kg -1 ·d -1 . Patients of the 3 group (n = 33) received standard treatment and UDCA combined with the use of arginine glutamate for 30 days. All LPO-AOP were performed at the beginning and at the end of treatment in all patients and 6 months after treatment in 20 patients in each group of observation. Results. A more significant decrease in the levels of intermediate and final products of lipid peroxidation in blood serum (from P < 0.05 to P < 0.001) was observed in patients of the 2 group and especially of the 3 group, as compared to the same values in the 1 group. The maximum effect of UDCA and glutamate arginine on the decrease in the formation of LPO toxic products in the blood was observed in the 3 group compared to the 2 group when studying the indices of diene conjugates and isolated double bonds 6 months after the treatment (P < 0.05). Conclusions. Combination therapy (non-medicamentous and medicamentous) with the addition of UDCA and glutamate arginine to the standard treatment in the comorbid course of NASH can be considered as a promising direction in the treatment of this category of patients, which allows to restore the basic indices of lipoperoxidation and antioxidant protection.

Hepatic manifestations of metabolic syndrome in boys with hypoandrogenism

Objective — to examine the morpho-functional state of the liver and the processes of free radical oxidation in boys with hypoandrogenism.Materials and methods. The study involved 47 adolescents with hypoandrogenism aged 13—18 years, who underwent a set of standard and special clinical and laboratory examination on the basis of the department of endocrinology SI «Institute of Children and Adolescents Health Care of the NAMS of Ukraine». Patients with hypoandrogenism were divided into groups depending on the index of masculinization. Mathematical processing of the study results was carried out using software packages SPSS Statistics 17.0, Excel.Results and discussion. It was found that complaints of abdominal pain and dyspeptic symptoms were observed in 62 % of cases. The conventional biochemical testing of liver function determined that the average levels of total bilirubin and liver enzymes were within normal range, suggesting that boys with hypoandrogenism probably had no significant violations of the functional state of the liver yet. Analysis of the lipid profile of children and adolescents with hypoandrogenism revealed that 75 % of patients had pathological changes in lipid levels, including 85 % with increased total cholesterol, 34 % with decreased HDL cholesterol and increased TG, 34 % with increased LDL cholesterol, 36 % with increased atherogenic coefficient. Atherogenic­chan­ges in the lipidogram increased with age. The study of indicators of free radical oxidation process revealed that in boys with hypoandrogenism the level of the final product of lipid peroxidation — malondialdehyde remained at the level of the control group, and the level of carbonated proteins tended to decrease with the increasing in the degree of delayed puberty. A significant reduction of the glutathione peroxidase level respectively to the deficiency of androgens was found. Thus, in adolescents with hypoandrogenism, a tendency towards the formation of the state of oxidative stress was revealed, which is confirmed by an increase of the integral coefficient of oxidative stress. Reducing the activity of the most powerful part of antioxidant system, in particular enzymatic, can lead to a «second hit» in the formation of non­alcoholic fatty liver disease and contribute to the transformation of liver steatosis into steatohepatitis. The results of ultrasound examination indicated the presence of functional disorders of the biliary tract in all boys with hypoandrogenism, and in one third of patients there were clear signs of steatohepa­tosis and gallstone disease. Conclusions. The results of the study indicated the formation of comorbid pathology of the hepatobiliary system in boys with hypoandrogenism. In 30 % of patients, ultrasound signs of steatohepatosis, atherogenic dyslipidemia and inhibition of antioxidant defense in the form of a significant decrease in the activity of glutathione peroxidase were detected. The results of the study indicate the necessity of inclusion in the diagnostic algorithm in boys with hypoandrogenism indicators of lipidogram, ultrasound of the liver and biliary tract, as well as the development of protocols for the prevention of hepatobiliary pathology, including the use of dietary correction, the prescription of hepatoprotectors with antioxidant activity, choleretic drugs.

The Effect of Mesedin on the Content of Oxidative Stress Biomarkers in the Brain Tissue in Ischemia

The effect of α2-adrenoblocker mesedin (2-(2-methylamino-4-thiazolyl)-1,4-benzodioxane hydrochloride) on the content of oxidative stress biomarkers in the brain tissue was well studied in ischemic disorders. The aim of this study is to reveal the possible mechanisms of the antihypoxic effect of mesedin. The quantitative changes of the final product of lipid peroxidation (LP)—malondialdehyde (MDA) and carbonyl derivatives of proteins — aldehyde-dinitrophenylhydrazones of neutral character (ADNPuv), ketone-dinitro-phenylhydrazones of neutral character (KDNPuv), aldehyde-dinitrophenylhydrazones of basic character (ADNPvs) and ketone-dinitrophenylhydrazones of basic character (KDNPvs) were studied in the brain tissue of rats (n = 56) under the condition of experimental ischemia caused by the ligation of the right common carotid artery. The study showed that one of the possible mechanisms of antihypoxic action of mesedin is its ability to prevent the accumulation of malondialdehyde and to limit protein carbonylation in brain ischemia. The data received demonstrates that mesedin could serve as a potential medicine for the correction of cerebrovascular ischemic disorders, for the reason that along with improving cerebral blood flow and preventing the development of morphological shifts and neurobehavioral disturbances in brain local ischemia, the medicine also mitigates the aggressive action of oxidative stress while protecting the brain tissue from the consequences of hypoxia.

Effect of Antioxidant activity of Astaxanthin in improving Human Spermatozoa lipid Peroxidation

Malondialdehyde (MDA) is the final product of lipid peroxidation which reacts with Thiobarbituric Acid (TBA) to produce red color and can be observed by spectrophotometry at a wavelength of 532 nm. Astaxanthin is an antioxidant that can reduce MDA by counteracting free radicals in lipid peroxidation in human spermatozoa. The objective of this study was to identify the antioxidant activity of astaxanthin in improving human spermatozoa lipid peroxidation, with parameters of color, odor, pH, volume, viscosity, concentration, morphology, motility and MDA levels. In this study, astaxanthin was given to 19 patients orally in a single dose of 8 mg per day for 30 days. As a negative control, six people were given with CMC Na placebo. MDA level measurement was performed using a spectrophotometer and the quality of spermatozoa was measured using WHO 2010 parameters. Significant difference in MDA level was found before and after astxanthin administration with a p-value of 0.022 (p 0.05), volume with p 0.965 (p>0.05) and pH with p 0.401 (p>0.05). In conclusion, astaxanthin can reduce lipid peroxidation, improve morphology, increase concentration and motility of human spermatozoa.

The Use of IR Fourier Spectroscopy of Saliva for Rapid Assessment of the Level of Lipid Peroxidation Products

Infrared spectroscopy of saliva is an express and non-invasive method of analysis, applicable for diagnostics of various diseases and for studying metabolic processes and adaptive changes in the body. The goal of this study was to determine possibility of analyzing the products of lipid peroxidation (LPO) by using IR spectroscopy of saliva on the example of oncological diseases. The study involved 203 patients with lung cancer (n = 40), breast cancer (n = 50) and the control group (n = 113). Saliva samples were collected in the morning after overnight fast. The content of LPO products (conjugated dienes, and trienes, Schiff bases, malonic dialdehyde MDA) was determined in all samples and the IR absorption spectra were recorded in the range of 500–4000 cm–1. In the IR spectra, an increase in the intensity of the absorption bands of lipids was observed; it corresponded to an increase in the total lipid content and correlated with the content of MDA, and a decrease in the intensity of vibrations of oxygen-containing groups, which corresponded to a negative correlation with secondary LPO products. Apparently, on the IR spectra, we simultaneously register both primary, intermediate, and final LPO products. Statistically significant regression equations were obtained, allowing to estimate the content of intermediate LPO products - conjugated triene, and Schiff bases. The proposed method allows to monitor LPO processes, as well as to characterize the direction of the equilibrium shift in these processes.