Effect of 1,3,6-trimethyl-5-hydroxyuracil succinate on the antioxidant system and free-radical processes in the liver of adult and old rats treated with carbon tetrachloride

2018 ◽  
pp. 55-59
Author(s):  
И.Д. Габдрахманова ◽  
В.А. Мышкин ◽  
Д.А. Еникеев ◽  
А.Р. Гимадиева
Keyword(s):  
Superoxide Dismutase ◽  
Free Radical ◽  
Carbon Tetrachloride ◽  
Antioxidant System ◽  
Complex Compound ◽  
Antiradical Activity ◽  
Conjugated Dienes ◽  
Experimental Animals ◽  
Old Rats ◽  
Radical Processes

Цель исследования: изучение влияния сукцината 1,3,6-триметил-5-гидроксиурацила на антиоксидантную систему и свободнорадикальные процессы в печени взрослых и старых крыс при воздействии тетрахлорметана. Методика. В эксперименте использованы половозрелые животные 12-месячного возраста со средней массой 250 г и старые животные 24-месячного возраста, средней массой 395 г по 30 особей в каждой возрастной группе. Токсическое поражение печени вызывали подкожным введением 50%-ного масляного раствора тетрахлорметана (ТХМ, 2 г/кг) в течение 4 сут. Одновременно с токсикантом опытным животным внутрибрюшинно вводили водный раствор коплексного соединения сукцинат-1,3,6-триметил-5-гидроксиурацила (2,5 мг/100 г) 3 раза в сут. в течение первых 4 сут. и в течение последующих 3 сут. 1 раз в сут. Контролем служили опытные животные, которым вводили физиологический раствор в том же объеме. Изучали окислительную модификацию белков, перекисное окисление липидов (по содержанию ТБК-реагирующих продуктов, уровню гидроперекисей липидов и содержанию диеновых конъюгатов). Состояние антиоксидантной системы оценивали по активности ферментов супероксиддисмутазы, каталазы и глутатионпероксидазы, определяемых биохимическими методами. Антирадикальную активность комплексного соединения и его составляющих субстанций исследовали в модельной системе «этилбензол-ледяная уксусная кислота» с вычислением константы К - скорости взаимодействия перекисных радикалов с молекулами изучаемого соединения в сравнении с эталонным антиоксидантом-ионолом с витамином Е. Результаты. Сукцинат + 1,3,6-триметил-5-гидрокси-урацила существенно снижает токсическое действие ТХМ на печень взрослых и старых крыс, устраняет дисбаланс в системах свободнорадикального окисления белков у старых крыс, статистически значимо улучшает показатели свободнорадикального окисления (СРО) липидов в печени взрослых и старых крыс: снижает уровень продуктов ПОЛ - гидроперекисей, диеновых конъюгатов, ТБК-реагирующих продуктов, а также улучшает работу антиоксидантной системы (АОС), повышая активность каталазы, супероксиддисмутазы и глутатионпероксидазы. Установлена высокая антирадикальная активность изучаемого препарата сопоставимая с активностью эталонного антиоксиданта ионола. Заключение. Сукцинат и его производные способны выступать как индивидуальные вещества с непосредственным антирадикальным механизмом действия, а не только как стимуляторы ферментативных систем антиоксидантной защиты. Aim. To study the effect of a complex compound, 1,3,6-trimethyl-5-hydroxyuracil succinate, on the antioxidant system and free radical processes induced by carbon tetrachloride in the liver of adult and old rats. Methods. The study used sexually mature animals aged 12 months and weighing 250 g and old animals aged 24 months weighing 395 g (total n= 60, 30 rats in each age group). Toxic damage of liver was induced by subcutaneous injections of a 50% oil solution of carbon tetrachloride (CTC) at 2 g/kg for 4 days. Together with the toxicant, experimental animals were injected with a water solution of a complex compound, succinate 1,3,6-trimethyl-5-hydroxyuracil, at a dose of 2.5 mg/100 g, i.p., 3 times per day for the first 4 days and once daily for the following 3 days. Experimental animals were used as controls, which were administered saline in the same volume. Oxidative modifications of proteins, lipid peroxidation (by levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and conjugated dienes) were studied. Condition of the antioxidant system was evaluated by activities of superoxide dismutase, catalase, and glutathione peroxidase using biochemical methods. Antiradical activity of the complex compound and its components was studied in a model system of ethylbenzene-glacial acetic acid; the K7 constant of the rate of peroxide radical interaction with molecules of the studied compound was compared with the reference antioxidant ionol with vitamin E. Results. Succinate +1.3.6-trimethyl-5-hydroxyuracil, considerably reduced TXM hepatotoxicity in adult and old rats; removed the disbalance in free radical systems of protein oxidation in old rats; significantly improved indexes of free-radical oxidation (FRO) of hepatic lipids in adult and old rats; decreased levels of LP products, hydroperoxides, conjugated dienes, and TBARS, and enhanced performance of the antioxidant system (AOS) by increasing activities of catalase, superoxide dismutase, and glutathione peroxidase. The study demonstrated a high antiradical activity of the study drug comparable with the activity of the reference antioxidant, ionol. Сonclusion. Succinate and its derivatives can perform as individual substances with a direct antiradical mechanism of action rather than as stimulators of enzymic systems of antioxidant defence.

scholarly journals THE STATE OF THE ANTIOXIDANT SYSTEM OF THE INTERNAL ORGANS IN RATS DURING BURN DISEASE

2014 ◽  
Vol 13 (3) ◽  
pp. 51-55
Author(s):  
L. G. Netyukhailo ◽  
T. A. Sukhomlin ◽  
Ya. A. Basarab ◽  
V. V. Bondarenko ◽  
S. V. Kharchenko
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Salivary Glands ◽  
Antioxidant System ◽  
The State ◽  
Antioxidant Systems ◽  
Free Radical Processes ◽  
Burn Disease ◽  
Radical Processes

The objective of research was to study the state of prooxidant and antioxidant systems in the tissues of the lungs, kidneys, pancreas and salivary glands at burn disease. The intensity of the free radical processes was evaluated on the basis of the content of malondialdehyde (MDA) and antioxidant system – based on the indexes of its enzymatic chain: superoxide dismutase and catalase in homogenates of the studied organs. It has been found that changes in experimental burn disease depend on the studied organs and the stage of burn disease. The activation of free radical processes observed in all investigated organs (lungs, kidneys, pancreas and salivary glands). Reactive oxygen species induce lipid peroxidation, which is a universal marker of tissue damage. MDA appears in the body during degradation of polyunsaturated fatty acids and it’s a marker of lipid peroxidation and oxidative stress. It was found the increasing of MDA in all organs, especially in the lungs and kidneys at stage of burn shock. Under these conditions it was observed the decrease of superoxide dismutase and catalase in all investigated organs. At burn disease there is development of disbalance between the action of prooxidant and antioxidant systems due to the activation of free radical processes.

State of the enzyme link of antioxidant protection in boys with hypoandrogenism

2020 ◽  
Vol 40 (4) ◽  
pp. 32-36
Author(s):  
L. K. Parkhomenko ◽  
◽  
L. A. Strashok ◽  
S. I. Turchina ◽  
G. V. Kosovtsova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Glutathione Peroxidase ◽  
Free Radical Oxidation ◽  
Conjugated Dienes ◽  
Delayed Puberty ◽  
Control Group ◽  
Antioxidant Protection ◽  
Radical Oxidation

Recently, interest in the problem of free radical oxidation in biological membranes, which is directly related to both the normal functioning of cells and the occurrence, course and outcome of many pathological conditions, has increased again in clinical medicine. The aim was to determine the role and impact of antioxidant defense in boys with hypoandrogenism. The study involved 75 adolescents with hypoandrogenism aged 13–18 years, who underwent a complex of clinical and laboratory examinations. All patients were conducted complex of anthropometric research and determination of the degree of delayed puberty, laboratory and instrumental examination. Free radical oxidation was determined by the levels of malondialdehyde, conjugated dienes, carbonated proteins, superoxide dismutase and catalase in the serum, and restored glutathione and glutathione peroxidase in whole blood. Based on their determination, the coefficient of oxidative stress was calculated. Statistical processing of results was performed using parametric and nonparametric methods. The study of indicators of the free radical oxidation process found that adolescents with hypoandrogenism have multidirectional changes in the oxidation of proteins and lipids, namely: the level of conjugated dienes increases, the concentration of malondialdehyde remains at the level of the control group, and the level of carbonated proteins tends to decrease. As for the activity of antioxidant protection enzymes, a significant decrease in the level of glutathione peroxidase was detected, while the level of superoxide dismutase and catalase remained at the level of normative indicators. Oxidative stress accompanies and is one of the pathogenetic links in the formation or maintenance of the state of hypoandrogenism in boys. This requires the use of antioxidants, the complex of which must be selected individually.

scholarly journals Effect of melatonin on antioxidant state under type II diabetes at rat

2013 ◽  
Vol 59 (4) ◽  
pp. 434-442 ◽  
Author(s):  
A.A. Agarkov ◽  
T.N. Popova ◽  
L.V. Matasova
Keyword(s):  
Diabetes Mellitus ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Blood Serum ◽  
Enzyme Activities ◽  
Type Ii Diabetes ◽  
Type Ii ◽  
Diabetes Mellitus Type Ii ◽  
Melatonin Administration ◽  
Radical Processes

The effect of melatonin on the intensity of free radical processes and activities of superoxide dismutase (SOD, EC 1.15.1.1.) and catalase (EC 1.11.1.6) has been investigated in liver and blood serum of rats with diabetes mellitus type II. The development of diabetes was accompanied by the increase in biochemiluminescence parameters and the enzyme activities studied. Melatonin administration changed the parameters studied towards control values.

scholarly journals The effect of biguanide derivatives on oxidative stress in rats with hyperglycemia

2018 ◽  
Vol 64 (3) ◽  
pp. 261-267
Author(s):  
E.I. Gorina ◽  
T.N. Popova ◽  
K.K. Shulgin ◽  
S.S. Popov ◽  
L.F. Panchenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Dna Fragmentation ◽  
Reduced Glutathione ◽  
Conjugated Dienes ◽  
Oxidative Modification ◽  
Regulatory Effect ◽  
Glutathione Antioxidant System ◽  
Primary Products ◽  
Radical Processes

The effect of the synthetic biguanide derivatives N-[imino(1-piperidinyl)methyl]guanidine (NIPMG) and 1,3-dimethyl-5-[(carbamimidamidomethanimidoil) amino]benzoyl-1,3dicarboxylate (DCB) on the degree of proteins oxidative modification (POM) and the DNA fragmentation, the content of the lipid peroxidation primary products – conjugated dienes (CD), and the activity of glutathione antioxidant system in the liver and heart of rats with experimental hyperglycemia was investigated. Administration of the biguanides (15.0 mg/kg) to hypoglycemic rats promoted reduction of the free radical processes intensity in the studied tissues. Data about CD and POM level changes in hyperglycemic rats treated by NIPMG and DKB correlate with the results of DNA fragmentation degree evaluation. At the same time, the activity of antioxidant enzymes (glutathione peroxidase and glutathione reductase), and the reduced glutathione content in the liver and heart of rats changed toward control values. For metformin, which was used as a comparison drug, changes in the studied parameters in the same direction were also found. These results indicate the ability of the tested biguanide derivatives to exhibit a positive regulatory effect on free radical homeostasis, reducing the degree of oxidative stress at this pathology.

scholarly journals Cytoprotective processes induced by the effect of L-arginin-L-glutamate in rats with experimental pathology of the gastroduodenal zone

2018 ◽  
Vol 9 (2) ◽  
pp. 300-307
Author(s):  
Y. M. Stepanov ◽  
L. A. Ponomarenko ◽  
O. A. Lykholat ◽  
T. M. Shevchenko ◽  
O. M. Khomenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Antioxidant Defense ◽  
Reduced Glutathione ◽  
Experimental Animals ◽  
Free Radical Processes ◽  
Experimental Pathology ◽  
Ulcerative Lesions ◽  
Gastroduodenal Zone ◽  
Radical Processes

The processes of effect of L-arginine-L-glutamate on peroxidation and slime-forming function of the stomach cells, the system of antioxidant defense in the blood, liver and brain tissues of rats with experimental pathology of the gastroduodenal zone have been investigated. The animals were divided into four groups. Group I – control group were rats injected intragastrically through a probe physiological solution. Group II included animals with erosive ulcerative lesions of the gastroduodenal zone. Modeling of the erosive ulcerative lesions was carried out by intragastric administration of medical bile (1 ml/100 g) in combination with immobilization-cold stress for 1 hour at + 4 ºС for a period of seven days. Rats of group ІІІ simultaneously received an intra-abdominal 4% solution of L-arginine-L-glutamate in a dose of 20 mg per 100 g of body weight at the same time as the erosive ulcerative lesions modeling. To clarify the role of NO-ergic mechanism of L-arginine-L-glutamate influence on the quantitative composition of mucins and free radical processes rats in group ІV with erosive ulcerative lesions were injected with non-selective NO-synthase inhibitor, L-NAME (L-NG-nitroarginine methyl ester), at a dose of 1 mg per 100 g at the same time as injections of 4% solution of L-arginine-L-glutamate. The simulation of erosive-ulcerative lesions of the gastroduodenal zone in the experimental animals was accompanied by the intensification of lipid peroxidation processes, the imbalance of the antioxidant defense systems and the development of oxidative stress in the blood, tissues of the stomach, liver and brain, which has tissue-specific features. In the blood of the animals, the activation of the enzymatic link of antioxidant defense did not compensate for free radical processes, as a result, the exhaustion of the reduced glutathione pool occurred, and the level of TBA-active products increased both in plasma and in erythrocytes. There was a depression of the enzymes of the antioxidant defense and a decrease in the level of recovered glutathione, indicating decompensating of the liver antioxidant protection systems in the liver tissue of the rats. In the experimental animals , formation of erosive ulcerative lesions was accompanied by destabilization of the oxidation-reducing processes in the brain, which led to the intensification of the lipoperoxidation. In the mucous membrane of the stomach of the experimental animals, the total number of protection factors – secretory mucins with a simultaneous structural change – decreased. The use of L-arginine-L-glutamate reduced the manifestations of oxidative stress in the stomach tissue of animals with experimental pathology and normalized the quantitative and qualitative composition of mucins. In the blood, liver tissues and brain of the rats, L-arginine-L-glutamate injections activated the enzymes of the first anti-radical linkage – superoxide dismutase and catalase contributed to the increase of the pool of reduced glutathione and the deceleration of free radical reactions. Investigation of reactions to the action of the inhibitor provides the basis for the hypothesis of the NO-mediated action of L-arginine-L-glutamate on the formation of S-nitrosothiols, as evidenced by the high level of reduced glutathione when the inhibitor is used.

Free-radical processes and the antioxidant system in the realization of the recovery function of sleep

2009 ◽  
Vol 35 (4) ◽  
pp. 455-459
Author(s):  
A. A. Nekhoroshii ◽  
T. A. Shustanova ◽  
A. A. Burikov ◽  
A. V. Balytskaya
Keyword(s):  
Free Radical ◽  
Antioxidant System ◽  
Free Radical Processes ◽  
Recovery Function ◽  
Function Of Sleep ◽  
Radical Processes

scholarly journals Evaluation of free radical processes in metabolism in combined hyperplasias of the female reproductive system

2005 ◽  
Vol 54 (5S) ◽  
pp. 38-38
Author(s):  
S. V. Chepur ◽  
Е. N. Popov ◽  
D. А. Niauri
Keyword(s):  
Free Radical ◽  
Antioxidant System ◽  
Reproductive System ◽  
Benign Tumors ◽  
Female Reproductive System ◽  
Free Radical Processes ◽  
Metabolic Reactions ◽  
Radical Processes

Relevance. It is known that free radical metabolic reactions are involved in the development and progression of the development of various destructive and hyperplastic processes in tissues. In this regard, the aim of this study was to compare the severity of disorders of the pro- and antioxidant system in single and multiple benign tumors of the female reproductive system.

Activity of the glutathione system and NADPH-generating enzymes under the action of melatonin during cerebral ischemia/reperfusion in rats

2018 ◽  
pp. 19-24
Author(s):  
Т.Н. Попова ◽  
О.А. Сафонова ◽  
А.О. Столярова ◽  
Т.И. Рахманова ◽  
Л.Ф. Панченко
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Cerebral Ischemia ◽  
Antioxidant System ◽  
Oxidative Metabolism ◽  
Reduced Glutathione ◽  
Ischemia Reperfusion ◽  
Free Radical Processes ◽  
Cerebral Ischemia Reperfusion ◽  
Radical Processes

Цель: В связи с ролью оксидативного стресса в патогенезе ишемических повреждений головного мозга изучить влияние препарата мелаксена (химический аналог гормона мелатонина) на активность антиоксидантных ферментов и некоторых ферментов окислительного метаболизма, способных лимитировать свободнорадикальные процессы при ишемии. Методика. В качестве объекта исследования использовали самцов белых лабораторных крыс. Индуцирование ишемии головного мозга у животных опытных групп осуществляли путем 30-минутной окклюзии общих сонных артерий, реперфузии достигали снятием окклюзоров. в головном мозге и сыворотке крови крыс изучали активность глутатионпероксидазы, глутатионредуктазы и глутатионтрансферазы, содержание восстановленного глутатиона, активность глюкозо-6-фосфатдегидрогеназы и НАДФ-изоцитратдегидрогеназы, способных выступать в роли поставщиков НАДФН для работы глутатионовой антиоксидантной системы. Активность ферментов и концентрацию восстановленного глутатиона определяли спектрофотометрически. Результаты. При действии мелаксена выявлено восстановление активности ферментов и уровня восстановленного глутатиона до значений близких к таковым у ложнооперированных животных. Полученные результаты могут быть объяснены с точки зрения торможения свободнорадикальных процессов за счет реализации антиоксидантных и нейропротекторных свойств мелатонина на фоне развития оксидативного стресса в условиях нарушения мозгового кровообращения, что приводит к снижению степени мобилизации антиоксидантной системы и некоторых ферментов окислительного метаболизма, которые, по-видимому, при реализации адаптивного ответа действуют как единая система. Заключение. Полученные результаты могут служить обоснованием дальнейшего исследования возможности применения мелатонин-корригирующих средств для фармакологической коррекции изменений метаболизма при развитии патологий подобного рода. Due to the involvement of oxidative stress in brain ischemic damage and to antioxidant properties of the hormone melatonin, it was relevant to study the effect of melatonin on antioxidant enzymes and some enzymes of oxidative metabolism that limit free radical processes in pathology. The aim was to study the effect of melaxen, a melatonin analogue, on activities of glutathione peroxidase, glutathione reductase, and glutathione transferase, content of reduced glutathione, and activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase, which can supply NADPH to the glutathione antioxidant system, in the brain and blood serum of rats with cerebral ischemia/reperfusion. Methods. White male rats were used in the study. Cerebral ischemia was induced by 30-min occlusion of common carotid arteries; reperfusion was induced by removing the occlusion. Activities of enzymes and concentration of reduced glutathione were measured spectrophotometrically. Results. Melaxen reversed the increased enzyme activities and the reduced glutathione level induced by the pathological conditions returning them to the control values. This can be explained by inhibition of free radical processes under the action of the antioxidant melatonin and its neuroprotective effect in oxidative stress associated with disorders of cerebral circulation. The result is decreased mobilization of the antioxidant system and some enzymes of oxidative metabolism, which act as a single system in the adaptive response. Conclusion. The study justified further investigation of the possibility for using melatonin-correcting agents for pharmacological correction of metabolic changes in such pathologies.

Effect of complex compounds of methyl derivatives of 5-hydroxyuracil with succinic acid on the antioxidant system and the morpho-functional state of the liver of old rats exposed to carbon tetrachloride

2017 ◽  
pp. 52-56 ◽  
Author(s):  
В.А. Мышкин ◽  
Д.А. Еникеев ◽  
И.Д. Габдрахманова ◽  
Д.В. Срубилин ◽  
А.Р. Гимадиева ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Succinic Acid ◽  
Functional State ◽  
Antioxidant System ◽  
Free Radical Oxidation ◽  
Complex Compounds ◽  
Corrective Effect ◽  
Old Rats ◽  
Methyl Derivatives ◽  
Derivatives Of

Цель. Изучение влияния комплексных соединений - 5-гидрокси-1,3,6-триметилурацила с сукцинатом (1) и 5-гидрокси-3,6-диметилурацила с сукцинтом (2) - на процессы перекисного окисления липидов (ПОЛ), антиоксидантную систему (АОС) и морфофункциональное состояние печени старых крыс при токсикозе, вызванном тетрахлорметаном. Методы. Опыты выполнены на 50 белых беспородных крысах-самцах, массой более 400 г. Токсическое поражение печени вызывали введением 50%-ного масляного раствора тетрахлорметана (ТХМ) (2 г/кг, п/к) в течение 4 дней [6]. Одновременно вводили исследуемые препараты - соединения 1, 2 и референтный препарат силимарин (50 мг/кг, в/бр) 3 раза в сутки в течение первых 4 дней и в течение последующих 3 дней 1 раз в сутки. Через 7 дней от начала введений исследовали сыворотку крови и печень. Результаты. Комплексные соединения 1 и 2 ограничивали некрозогенное действие ТХМ частично сохраняли функционально-метаболическую активность за счет благоприятного влияния на ферменты (АсАТ, ЩФ), содержание общего билирубина и холестерина в крови, а также за счет частичной нормализации нарушенного равновесия ПОЛ/АОС. Комплексное соединение 5-гидрокси-1,3,6-триметилурацила с сукцинатом более эффективно, чем соединение 2, уменьшало интенсивность и распространенность дистрофических и некротических процессов у старых крыс и существенно ограничивало выраженность гепатотоксического действия ТХМ. Заключение. Защитное действие 5-гидрокси-1,3,6-триметилурацила с сукцинатом было связано с корригирующим влиянием на глутатионовую и ферментативную системы антиоксидантной защиты. The influence of two new complex compounds of methyl derivatives of 5-hydroxyuracil with succinic acid on the antioxidant system and morpho-functional state of the liver of old rats exposed to carbon tetrachloride has been studied experimentally. The aim was to study the influence of complex compounds - 5-hydroxy -1,3,6 - trimethyluracil succinate (1) and 5-hydroxy-3,6-dimethyluracil succinate (2) - on the processes of free radical oxidation, antioxidant system regulating these processes and morpho-functional state of the liver of old rats exposed to carbon tetrachloride. Results. Complex Compounds 1 and 2 used prophylactically in old rats ( 50 mg/kg three times/day х 4 intraperitoneally, then 50 mg/kg once/ per day x 3 intraperitoneally) have been shown to limit necrosogenic effects of TCR ( 2 g/kg/day><4 subcutaneously), to preserve partially functional - metabolic activity due to favorable effects on enzymes (AST, alkaline phosphatase), total blood bilirubin and cholesterol and also due to partial normalization of POL/AOS imbalance. According to most indicators, Compound 1 turns out to be more effective and comparable to the effect of the silymin hepatoprotector. Conclusion. The cCompound 1 reduced the intensity and prevalence of dystrophic and necrotic processes of cellular reactions of the liver tissues in old rats and limited significantly the severity of TCR hepatotoxicity due to a corrective effect on glutathione and enzymatic antioxidant defense system.

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