CHARACTERISTICS OF REDOX STATUS IN MALE AND FEMALE RATS WITH EXPERIMENTAL DIABETES MELLITUS, GUERIN'S CARCINOMA AND ASSOCIATED PATHOLOGY

Taking into account cancer and diabetes comorbidity, the role of free radicals in these conditions and the dependence of pathological processes on the gender of animals, the aim of the study was to examine lipid peroxidation (LPO) intensity and the activity of the key antioxidant enzyme superoxide dismutase (SOD) in the heart, kidneys, liver, and in tumors of male and female rats with diabetes mellitus (DM), Guerin's carcinoma (GC) or both diseases. Materials and Methods. The study included 80 white nonlinear male and female rats (180–220 g). The animals were divided into 4 groups, each group included 10 animals (either male or female). At the time of GC inoculation, the blood glucose level in animals with alloxan diabetes was 25.4±1.2 mmol/L. The authors used conventional spectrophotometric methods to examine the content of malondialdehyde (MDA), diene conjugates (DC), and SOD activity. Statistical analysis was performed using Statistical analysis software Statistica 10.0. Results. The most pronounced changes in the studied parameters were found in the heart of female rats with isolated GC and associated diabetes mellitus: more than a threefold increase in MDA, a significant increase in DC against the background of an increase in SOD activity (by 5.5–6.3 times in comparison to intact animals). The amount of MDA in GC tissue depended on the tumor size: the maximum increase in both parameters was observed in male rats with GC growth and associated DM. Conclusion. The changes in the content of LPO products and SOD activity in the heart, kidneys, and liver of rats with diabetes mellitus and tumor growth depend on the type of the examined tissue and the gender of the animals. Disorders of the redox status found in the heart tissue can make a significant contribution to cardiopathology, which is often observed in diabetes mellitus and malignant tumor growth. Key words: diabetes mellitus, Guerin's carcinoma, rats, combined pathology, heart, kidneys, liver, malondialdehyde, diene conjugates, superoxide dismutase. Учитывая коморбидность рака и диабета, роль свободнорадикальных процессов при этих состояниях и зависимость течения патологических процессов от пола животных, целью исследования явилось изучение интенсивности перекисного окисления липидов (ПОЛ) и активности ключевого антиоксидантного фермента супероксиддисмутазы (СОД) в сердце, почках, печени, а также в опухоли крыс разного пола при сахарном диабете (СД), карциноме Герена (КГ) и при их сочетании. Материалы и методы. В исследование были включены 80 белых нелинейных крыс обоего пола массой 180–220 г, разделенных на 4 группы по 10 животных каждого пола. На момент перевивки КГ уровень глюкозы в крови животных с аллоксановым СД составил 25,4±1,2 ммоль/л. Содержание малонового диальдегида (МДА), диеновых конъюгатов (ДК) и активность СОД исследованы общепринятыми спектрофотометрическими методами. Статистический анализ проведен с использованием программы Statistica 10.0. Результаты. Наиболее выраженные изменения изученных показателей выявлены в сердце самок при изолированной КГ и КГ, растущей на фоне СД: более чем трехкратное увеличение МДА, значимый прирост ДК на фоне повышения активности СОД в 5,5–6,3 раза относительно интактных животных. В ткани КГ прослеживалась зависимость степени выраженности увеличения содержания МДА от размеров опухоли: максимальное увеличение обоих показателей наблюдалось у самцов при росте КГ на фоне СД. Выводы. Направленность изменения содержания продуктов ПОЛ и активности СОД в сердце, почках и печени крыс при СД и опухолевом росте зависит от типа исследованной ткани и пола животных. Обнаруженные в ткани сердца нарушения редокс-статуса могут вносить значимый вклад в развитие кардиопатологии, часто наблюдаемой при СД и злокачественном росте. Ключевые слова: сахарный диабет, карцинома Герена, крысы, сочетанная патология, сердце, почки, печень, малоновый диальдегид, диеновые конъюгаты, супероксиддисмутаза.

Lipid peroxidation functional state changes in patients with obstructive jaundice depending on the level of bilirubin in the blood

Obstructive jaundice (OJ) is the most common syndrome among diseases of the hepatopancreatoduodenal region and is found in 12-45% of cases. OJ may be benign and malignant etiology. Despite the evidence of the participation of bilirubin in reducing the bactericidal properties of neutrophils, there are no data currently on changes in the functioning of the antioxidant defense system depending on the level of bilirubin in the blood of patients with OJ of various origins. Research in this direction reveals the possibility for the development of pathogenetic recommendations for influencing these links of the pathogenesis of the disease. The study included men with OJ of non-malignant (OJNMG) (n = 47; mean age - 52.02 ± 5.18 years) and OJ of malignant genesis (OJMG) (I-II stages of the malignant process) (n = 45; mean age - 53.02 ± 4.8 years), divided into three subgroups, depending on the level of bilirubin in the blood. The indicators of practically healthy men as a control (n = 50, average age - 48.7 ± 3.9 years) were used. Spectrophotometric and statistical research methods were used. A statistically significant decrease of superoxide dismutase, glutathione-S-transferase, glutathione-peroxidase, ceruloplasmin, an increase in the values of diene conjugates, malondialdehyde in the group of patients with OJNMG relative to the control was revealed, regardless of the level of bilirubin in the blood. The presence of malignant genesis of the disease with more intense changes in the studied parameters relative to control is accompanied. Comparison of indicators between groups of patients with OJ of different genesis showed a decrease in the values of glutathione-S-transferase and an increase in the level of diene conjugates in patients with OJMG and the level of bilirubin less than 60 μmol / L, as well as an increase in the content of diene conjugates in patients with OJNMG and a level of bilirubin 60- 200 μmol / L in comparison with the corresponding groups of patients with OJNMG. Thus, both in the groups with OJNMG and in the groups with OJMG, there is a significant decrease in the activity of the main antioxidant enzymes and an increase in lipid peroxidation products, regardless of the level of bilirubin in the blood. The presence of malignant genesis is characterized by more intense differences. The revealed changes can serve as additional criteria for optimizing the diagnosis and treatment of this cohort of patients.

Autonomous regulation of antioxidant protection and protein exchange in chickens

The tone of the autonomic nervous system, protein metabolism and the activity of the antioxidant system in Cobb-500 cross chickens aged 35 and 60 days were researched. The experiment involved 24 chickens, 8 in each group. In birds, the tone of the autonomic nervous system was determined by the method of variation pulsometry by recording the influence of the sympathetic and parasympathetic systems on the heart rate in chickens. The effect was determined by counting one hundred consecutive cardio intervals and the time interval between each cardiocycle. Venous blood samples were taken from each individual at the age of 35 and 60 days to determine protein metabolism (total protein, albumin, globulins), enzymatic and non-enzymatic links of the antioxidant system and lipid peroxidation depending on the tone of the autonomic nervous system. It was found that the antioxidant level in chickens with a predominance of the sympathetic division prevailed in all other groups regardless of the age of the bird. At 35 days of age, plasma concentrations of diene conjugates were significantly higher in normatonics and vagotonics (P ˂ 0.05). There was a higher level of activity of ketodienes and Schiff bases in chickens with a predominance of the sympathetic division of autonomic nervous regulation compared with normotonics and vagotonics (P ˂ 0.01). The content of total protein, albumin and globulins prevailed in normotonic hens and was the lowest in vagotonic hens at the age of 35 days. The two-month-old bird with a dominant parasympathetic division of the autonomic nervous system and normotonic hens had the highest levels of total protein, globulins, and conversely, sympathicotonic hens outnumbered the latter in albumin levels. Histidine content was highest in chickens with a balanced type of autonomic nervous system compared to sympathicotonics and vagotonics (P ˂ 0.05). The concentration of sulfur-containing amino acid methionine was highest in vagotonic chickens (P < 0.05) compared with sympathicotonics. Threonine was highest in sympathicotonics compared with other groups of animals and significantly outweighed vagotonics (P < 0.05). The level of lipid peroxidation products in 60-day-old sympathicotonic chickens was consistently higher in contrast to normotonics and vagotonics. At the same time there was the smallest increase in the activity of diene conjugates and ketodienes (P < 0.05) in chickens with a dominant sympathetic division of the autonomic nervous system, which indicates a slowdown in the accumulation of the final products of lipid peroxidation. It was found that the predominance of sympathetic tone is characterized by low activity of enzymes of the antioxidant system and tocopherol (P < 0.001, P < 0.01) at 35 and 60 days of age. Indicators of the activity of the antioxidant system had the highest level in vagotonic chickens of the studied age period (P < 0.05, P < 0.01, P < 0.001). The relationship between catalase and tocopherol levels in vagotonic chickens at 35 days of age, which increases at 60 days of age r = 0.53 (P < 0.01) was found.

The systemic pro- and antioxidant processes in preschool children with recurrent acute respiratory diseases

Background. The imbalance of innate defense early mechanisms in children from pathogens — peroxidation and antioxidant system, can lead to a decrease in the efficiency of the entire immune system. The study of the lipid peroxidation (LPO) and antioxidant protection (AOP) status in children with recurrent acute respiratory diseases will complement the scientific data on the antimicrobial immunity formation processes. The study was aimed to increase the information value of timely detected pro- and antioxidant processes disorders in children with recurrent acute respiratory diseases by studying the primary, secondary, tertiary, and quaternary compounds of LPO and AOP in the serum. Materials and methods. Sixty children aged from 2 to 5 years were examined. Two groups were formed: group 1 — children with respiratory acute infectious more than six times per year (n = 30); group 2 — children with respiratory acute infectious six or fewer times per year (n = 30). Results. The children in group 1 more often presented with high serum levels of lipid hydroperoxides (by 80.0 %; p < 0.05), diene conjugates (by 80.0 %; p < 0.05), malonic dialdehyde (76.7 %; p < 0.05), diene ketones (76.7 %; p < 0.05), Schiff bases (76.7 %; p < 0.05). ceruloplasmin (80.0 %; p < 0.05), superoxide dismutase (80.0 %; p < 0.05), glutathione peroxidase (86.7 %; p < 0.05), catalase activity (86.7 %; p < 0.05). The values of retinol, tocopherol, ascorbic acid in children in the observation groups did not differ statistically significantly. Conclusions. The children aged from 2 to 5 years old with recurrent acute respiratory diseases have an imbalance of the LPO and AOP systems. It was characterized by a simultaneous increase in the serum content of the primary, secondary, and end-products of LPO, enzymes of anti-peroxide and anti-oxygen protection against the background of the lack of adaptive increase in the content of anti-radical compounds.

Activity of the antioxidant defense system of the carp organism under the influence of stress factors and the use of milk thistle in feeding

Intensification measures in carp farming are accompanied by the emergence of stressors, which negatively affects the productive characteristics and functional state of organs and systems of fish. One of the ways to counteract their negative effects on the body is to stimulate the antioxidant defense system. The aim of the study is to analyze the effectiveness of plant additives with antioxidant properties of milk thistle in carp feeding, under optimal housing conditions (Experiment I) and under the influence of stress factors common in fish farming, namely: pollution of the aquatic environment with nutrients (Experiment 2) and this pollution. complexes with a decrease in the content of dissolved oxygen in water (Experiment 3). The studies used one-year-old carp, which were divided into experimental and control groups within each of the three variants of the experiment. Control groups of fish received feed with a protein content of 23%. Carp of the experimental groups in addition to the feed by granulation was introduced crushed seeds of milk thistle in the amount of 5%. Experimental feeding lasted 20 days. In accordance with the generally accepted methods and purpose of the experiment in fish farming, the physicochemical parameters of the aquatic environment are provided. Indicators of lipid peroxidation (LPO) and activity of the body's antioxidant defense system (ANS) were analyzed. It was determined that when feeding thistle carp under annual conditions under optimal growing conditions in the muscles of the experimental group there is some tendency to increase the content of catalase (by 14.6%), and the content of SOD, TBC products and diene conjugates is at the same level as and in control. In the hepatopancreas, on the other hand, the level of catalase decreases somewhat relative to control and there is a tendency to reduce TBA products and the content of diene conjugates is reduced by 75% (p <0.05). When feeding milk thistle for contamination of the aquatic environment with nutrients in the muscles almost three times the content of SOD (p˂0.01). The content of catalase tends to decrease, and the content of TBA products and diene conjugates increases by 51%. In the hepatopancreas there is a tendency to decrease all of the above indicators relative to the control group. It was found that the introduction of milk thistle in the feed under conditions of complex exposure to stressors in the muscles increases the content of SOD (p˂0,001). The content of catalase and TBA products decreases slightly in the hepatopancreas, the content of SOD (p˂0.001) and diene conjugates (p˂0.001) increases. Therefore, the antioxidant properties of milk thistle are more pronounced as a result of use in the feeding of carp in the presence of environmental stressors, compared with optimal growing conditions.

SOME FEATURES OF DIFFERENTIATION OF CONCENTRATION OF DIENE CONJUGATES IN BLOOD SERUM AND TISSUE OF RATS

One of the mechanisms for maintaining homeostasis in the body is lipid peroxidation (LPO). The influence of external and internal factors affecting the body can change the dynamics of LPO processes, causing numerous disorders in the functioning of organ systems. The dynamics of LPO processes in the early stages can be estimated from the change in the concentration of intermediate oxidation products - diene conjugates (DC). The purpose of our study was to identify the features of the differentiation of the distribution of the concentration of diene conjugates in the blood serum and tissues of white outbred rats. New results of nonparametric correlation analysis are presented to assess the relationship of the distribution of the concentration of diene conjugates in the blood serum and tissues of white outbred rats.

Enzymatic-metabolic support of oxidative homeostasis in patients with hypoxic-ischemic brain lesions in the stages of cardiosurgical interventions

To study the features of enzymatic and metabolic support of oxidative homeostasis in patients with hypoxic-ischemic brain lesions before and after cardiac surgery using artificial circulation we examined 38 patients, in particular: ischemic stroke — 14 people, encephalopathy — 15 people, severe cognitive dysfunction — 9 people ; diagnosis of neurological status was performed according to clinical protocols. Clinical and biochemical study was performed at the preoperative (3—5 days) and postoperative (5—7 days) stages: determined the content of superoxide dismutase, glutathione peroxidase, catalase in erythrocytes and α-tocopherol acetate in the serum of the blood, as well as the product cells: diene conjugates, metabolites of nitritanion in plasma. Variation statistics, probabilistic distribution of data with the subsequent estimation of reliability of results are applied; relative biochemical parameters were used: metabolic index, metabolic coefficient and metabolic effect for each. Standard methods using the program adapted to the “Excel” environment were used for calculations. The obtained data support the formation of patients with specific postoperative enzymatic-metabolic support of oxidative homeostasis, which should be considered as one of the triggers of hypoxic-ischemic brain lesions. In particular, at the level of the enzymatic chain of pro-, antioxidant protection and at the level of metabolic processes associated with peroxidation of phospholipids of cell membranes, a number of significant metabolic effects were revealed, which are generalized due to secondary oxidation products and NO‑dependent metabolites.

Results of the use of a sorbent in a carp feed with signs of mycotoxin contamination

Purpose. The aim of the work was to study certain morpho-physiological parameters of carp as a result of additional introduction of a mycotoxin sorbent to a feed with signs of spoilage. Methodology. During 2019–2020, two experiments were conducted in the laboratory. The first one included 7 groups-analogues of age-1+ Nyvky carp, 20 fish in each group, with an average weight of 22.5 g. The control group of fish was fed for 24 days with a compound feed with signs of spoilage, «Mykosorb» was additionally added to the diet of the experimental groups in the amounts of 0.05, 0.1; 0.15; 0.2; 0.25 and 0.4%, respectively. The second group included 4 groups of age-1+ fish, 12 fish in each group, with an average weight of 20.0 g. The diet of the control group was identical to that of the first experiment, and the experimental groups with the addition of 0.05, 0.075 and 0.1% of «Mycosorb», respectively. During the study, optimal conditions for keeping fish were provided. Fish after were measured and weighed at the end of the experiment and their weight gains were analyzed according to generally accepted methods in fish farming. The activity of antioxidant enzymes and the content of lipid peroxidation products depending on the composition of the diet were studied. Findings. The studies used compound feed with signs of spoilage as a result of violation of their storage technology, which identified three groups of toxins: Aflatoxin B1, Zearalenone and Deoxynivalenol. As a result of the first stage of the study, the rates of application of mycotoxin sorbent into the diet of carp at amounts of 0.05 - 0.2% were determined. At the same time, there was no clear proportional pattern of changes in the average weight of fish depending on the amount of introduction of «Mycosorb», the value increased in all experimental groups compared to the control by 0.4 – 15.2%. Muscles of age-1+ fish were found to have higher (p<0,001) catalase activity after application of 0.15% of the test drug by 1.4 times, 0.2% — by 46%, 0.25% — by 69 and 0.4% — by 79%. Superoxide dismutase activity also increased, except for the groups of 0.2, 0.25 and 0.4% of «Mycosorb». There was a tendency of 21.0 and 22.6% decrease in the content of diene conjugates as a result of feeding 0.05 and 0.1% sorbent and some increase as a result of feeding 0.15; 0.2; 0.25 and 0.4% additives. Studies of the next stage showed that addition of «Mykosorb» at the rate of 0.05, 0.075 and 0.1% to the feed, the average weight of age-1+ carp in the experimental groups increased by 45.4; 37.2 and 30.3%, the condition factor — by 41.9; 40.8 and 42.7%, the relative growth rate is 4.3; 5.9 and 4.6 times, respectively. The fish body height to length ratio was lower by 10.3, 7.0 and 7.4% relative to the control group. Addition of 0.05, 0.075 and 0.1% of «Mycosorb» increased resistance of fish due to an increase in the hepatopancreatic activity of antioxidant enzymes: superoxide dismutase by 28.3, 30.5 and 5.0% and catalase by 56.5 (p<0.001), 55.5 (p<0.001) and 46.3% (p<0.05). At the same time, addition of 0.05 and 0.1% of «Mykosorb» increased the content of diene conjugates by 11.3 (p<0.01) and 12.3% (p<0.01), TBC-active products by 19.7 (p<0.05) and 13.2%. Originality. For the first time, the feasibility of addition of the mycotoxin sorbent «Mykosorb» into the feed with signs of spoilage was studied. The effect of feeding age-1+ carp with diets of various compositions on some morpho-physiological parameters of carp in the conditions of model tests was carried out. Practical value. Additional weigh gains and improvements of the antioxidant defense system of the carp organism were observed. The use of «Mykosorb» in carp feeding allows reducing the negative impact of low quality feed on fish body. Key words: carp, feed, feed additives, mycotoxins, sorbent, morphological parameters, growth, antioxidant defense system

CONTENT OF PRIMARY AND SECONDARY LIPID PEROXIDATION PRODUCTS IN SUBCELLULAR FRACTIONS OF CARDIOMYOCYTES DURING MYOCARDIAL INFARCTION IN RATS IN AN EXPERIMENT AND THEIR CORRECTION BY TRANSPLANTATION OF MESENCHYMAL STEM CELLS

Experimental modeling of myocardial infarction in rats was carried out by ligation of the anterior intergastric artery after the first division. There were 3 groups of 20 animals each: control group I — to verify normal parameters, group II — a model of myocardial infarction, and group III — animals which, after modeling myocardial infarction, underwent transplantation of mesenchymal stem cells. The level of lipid peroxidation products — diene conjugates and malondialdehyde — was studied by spectrophotometry. Comparison of the content and their ratio in the cytoplasm and mitochondria of myocardiocytes was carried out. It turned out that transplantation of mesenchymal stem cells significantly levels the activation of lipid peroxidation processes in subcellular fractions of cardiomyocytes, which is accompanied by a decrease in the primary and secondary products of oxidative stress. The ratio of malondialdehyde to diene conjugates both in the cytoplasm and in the mitochondria of cardiomyocytes after transplantation returned to control values. This indicates the normalization of physiological processes with underlying ischemic heart damage. The results indicate the cytoprotective effect of mesenchymal stem cell transplantation and the preservation of a larger number of cell pools, compared with the control group of animals that did not receive any treatment.

Protective effect of ademetionine, cytoflavinum and dihydroquercetin in the liver of rats exposed to toxic effects of valproate sodium

Введение. Вальпроат натрия влияет на метаболизм гамма-аминомасляной кислоты, предотвращая развитие эпилептических приступов. Многие метаболиты вальпроата натрия потенцируют его клинический эффект, однако, именно они могут приводить к развитию хронической интоксикации с поражением печени. Цель - оценка протекторного эффекта адеметионина (гептрала), цитофлавина и дигидрокверцетина у крыс, подвергнутых токсическому влиянию вальпроата натрия (депакина). Методика. Животным контрольной группы вводили вальпроат натрия в токсической дозе 600 мг/кг интрагастрально 1 раз в день в течение 28 сут. Крысам опытных групп вводили вальпроат натрия в той же дозе с одновременным введением адеметионина, цитофлавина или дигидрокверцетина. Животные выводились из эксперимента на 7-, 14-, 21- и 28-е сут. В гомогенате печени определяли стандартными спектрофотометрическими методами концентрацию диеновых конъюгатов, малонового диальдегида, восстановленного глутатиона и активность ферментов метаболизма глутатиона: глутатионредуктазы, глутатионпероксидазы и глутатионтрансферазы. Результаты. При токсическом воздействии вальпроата натрия в ткани печени развивались процессы гиперпероксидации липидов, которые подтверждались значительным повышением уровня диеновых конъюгатов и малонового диальдегида. Концентрация глутатиона снижалась начиная с 14-х сут эксперимента. Активность глутатионредуктазы повышалась к 14-м сут, а затем к 28-м сут практически достигала значений интактных животных. Активность глутатионтрансферазы начинала снижаться с 14-х сут и сохранялась низкой до конца исследования. Активность глутатионпероксидазы повышалась с 14-х сут эксперимента, достигая максимума к 28-м сут. Протекторный эффект адеметионина при токсическом воздействии вальпроата натрия выражался в снижении содержания диеновых конъюгатов и малонового диальдегида. Одновременно происходила активация системы глутатиона: повышалась активность глутатионтрансферазы и глутатионредуктазы. Антиокислительное действие цитофлавина проявлялось в основном на 1-й нед эксперимента: концентрация диеновых конъюгатов и малонового диальдегида снижалась, активность глутатионредуктазы и глутатионтрансферазы повышалась. Дигидрокверцетин также оказывал антиокислительное действие: концентрация диеновых конъюгатов и малонового диальдегида снижалась. Активность глутатионредуктазы и глутатионтрансферазы увеличивалась по сравнению с контрольными животными. Заключение. Вальпроат натрия в токсической дозе приводит к статистически значимому повышению уровня продуктов перекисного окисления липидов и снижению антиокислительной защиты системы глутатиона в печени крыс. Адеметионин, цитофлавин и дигидрокверцетин способствуют восстановлению баланса системы перекисного окисления липидов и антиоксидантной защиты в печени крыс при токсическом влиянии вальпроата натрия. Наиболее перспективным препаратом защиты является адеметионин, так как он наиболее существенно снижает концентрацию диеновых конъюгатов, малонового диальдегид и повышает активность системы глутатиона на протяжении 28 сут эксперимента. Background. Sodium valproate affects metabolism of gamma-aminobutyric acid to prevent the development of epileptic seizures. Many valproic acid metabolites potentiate its clinical effect; however, specifically these metabolites may result in chronic intoxication with liver damage. Aim: To evaluate the protective effect of ademetionine (Heptral), cytoflavin, and dihydroquircetin in rats exposed to the toxic action of sodium valproate (Depakene). Methods. Animals of the control group were administered valproate sodium at a toxic dose of 600 mg/kg, intragastrically. Rats of the experimental group were administered valproate sodium at a dose of 600 mg/kg with simultaneous administration of ademetionine, cytoflavin and dihydroquercetin. The duration of drug administration in all groups was 7 days, 14 days, 21 days, or 28 days. The contents of diene conjugates, malonic dialdehyde, reduced glutathione, and the activity of glutathione reductase, glutathione peroxidase, and glutathione transferase were measured in liver homogenates with standard spectrophotometric methods. Results. Under the toxic effects of valproate sodium in liver tissue, a significant increase in the contents of diene conjugates and malonic dialdehyde was found. The glutathione concentration decreased starting from day 14 of the experiment. The glutathione reductase activity increased by day 14 and practically reached the values of intact animals by day 28. The glutathione transferase activity began decreasing on day 14 and remained low until the end of study. The glutathione peroxidase activity increased starting from day 14 and reached maximum by day 28. The protective effect of ademetionine was manifested by a decrease in the contents of diene conjugates and malonic dialdehyde. There was a simultaneous activation of the glutathione system evident as increased activities of glutathione transferase and glutathione reductase. An antioxidant effect of cytoflavin was manifested mainly at the 1st wk of the experiment. The concentration of diene conjugates and malonic dialdehyde decreased, the activity of glutathione reductase increased, and the activity of glutathione transferase increased. Dihydroquercetin also had an antioxidant effect since the concentration of diene conjugates and malonic dialdehyde decreased. The activity of glutathione reductase and glutathione transferase increased. Conclusion. Sodium valproate significantly increased concentrations of lipid peroxidation products and impaired the glutathione antioxidant defense in the rat liver. Ademetionine, cytoflavin and dihydroquercetin help to restore the balance of lipid peroxidation and antioxidant protection in the rat liver during the toxic effects of valproate sodium. The most effective drug was ademetionine, since within 28 days, it significantly decreased the concentration of diene conjugates and malonic dialdehyde, and it increased the activity of the glutathione system.