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

Author(s):  
Л.В. Охремчук ◽  
И.Ж. Семинский

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.

2021 ◽  
Vol 102 (2) ◽  
pp. 199-205
Author(s):  
G R Kuramshina ◽  
F Kh Kamilov

Aim. To study changes in the glutathione system in bone tissue during chronic intoxication with elements contained in copper-zinc pyrite ore and antioxidant vitamin administration. Methods. 36 mature male white rats were divided into three groups (control, comparison, experimental). The rats of the experimental and comparison groups received intragastrically copper-zinc pyrite ore powder in a 2% starch solution as a suspension at a dosage of 60 mg/100 g bodyweight daily for three months. During the last month, the experimental group received an antioxidant vitamin preparation (the complex of vitamins with a trace element) containing -tocopherol, -carotene, ascorbic acid and selenium. The content of reduced glutathione, free thiol groups in proteins, the activity of glutathione peroxidase, glutathione transferase, glutathione reductase, gamma-glutamyl transferase, and glucose-6-phosphate dehydrogenase were determined in homogenates derived from femoral epiphysis. The statistical analysis of the results was performed using Statistica 6.0 software. The median (Me) and percentiles (Q1 and Q2) were calculated, a non-parametric MannWhitney U test was carried out to compare study groups. Results. Chronic intoxication with elements contained in copper-zinc pyrite ore causes impairment of the glutathione system in bone tissue. Intoxicated rats showed a decrease in the reduced glutathione content to 71.9% (р=0.014) and free sulfhydryl groups of proteins to 77.8% (р=0.0143), inhibition of glutathione-dependent antioxidant enzymes activities, and disruption of the glutathione reduction system in tissues, compared to the control group. Antioxidant vitamin administration increased the levels of reduced glutathione and free thiol groups of proteins, activated the enzymes involved in the glutathione system: the reduced glutathione content increased to 94.8% (p=0.2132), glutathione peroxidase activity to 85.7% (p=0.0432), glutathione transferase up to 94.3% (p=0.5251), glutathione reductase up to 86.1% (p=0.0442) compared to the control group. Conclusion. Chronic intoxication with metals contained in copper-zinc pyrite ore leads to decreasing the content of reduced glutathione and free thiol groups of proteins in bones along with reducing glutathione reductase and glucose-6-phosphate dehydrogenase activities, inhibition of glutathione peroxidase and glutathione transferase; an antioxidant vitamin administration increases the activity of glutathione reduction enzymes in bone tissue, the content of reduced glutathione and free sulfhydryl groups of proteins, the activities of glutathione peroxidase and glutathione transferase.


Author(s):  
A. Yurchenko ◽  
D. Krenytska ◽  
M. Tymoshenko

The state of the glutathione-dependent link of the antioxidant blood system of rats under obesity development and with the compatible consumption of the kidney bean (P. vulgaris) pods extract was studied. Glutathione system forms functional basis of organism antioxidant defense system and disturbances in its work can lead to a number of serious cytotoxic and destructive lesions. Glutathione system constituent elements has its own glutathione and enzymes, which catalyze the reaction of its reverse transformation. These include glutathione peroxidase, glutathione transferase, and glutathione reductase. It is known that the water kidney bean (P. vulgaris) pods extract has hypoglycemic properties. However, complex studies of the polyfunctional action of this extract in obesity are absent. The obtained results indicate a decrease in the overall potential of the glutathione system in animals on a high-calorie diet. It has been established that glutathione peroxidase activity (GP) decreases in the serum of rats under experimental obesity, also glutathione transferase (GT) and glutathione reductase (GR) activity increase compared to the corresponding values in control animals. Our results demonstrated the concentration decrease of recovered glutathione (GSH) under consumption of high-calorie diet compared to the control. The findings after 6-th weeks of kidney bean (P. vulgaris) pods extract consumption indicate the positive modulating effect of this extract on the content of GSH and the activity of GP, GT and GR in rats with the obesity development. Probably, the consumption of this extract leads to attraction of the investigated components of the antioxidant system to the reactions of neutralization of toxic free radical compounds that were formed against the background of the development of obesity. Further studies may serve as the basis for the development of new therapeutic or medicinal preparations that based on the kidney bean (P. vulgaris) pods extract, because of still no consensus on the treatment of obesity.


2016 ◽  
Vol 1 (61) ◽  
pp. 46-51
Author(s):  
Литовченко ◽  
Ekaterina Litovchenko ◽  
Коршунова ◽  
Natalya Korshunova ◽  
Доровских ◽  
...  

The purpose of this research was to study the possibility of using of food products from a mixture of Hypericum perforatum (HP) and Rhodiola rosea (RR) for the stimulation of the body´s compensatory responses to the conditions of high and low temperatures. Experiments have been conducted on experimental animals (150 white mongrel rats) in accordance with generally accepted methodological approaches. Antioxidant effects in the organism of white rats have been studied at the initiation of the processes of lipid peroxidation by the introduction of carbon tetrachloride. We were determined the products of lipid peroxidation (diene conjugates, hydroperoxides of lipids, malonic dialdehyde) for the evaluation of antioxidant effect in accordance with generally accepted methodological approaches. Researches of cold and heat adaptation reactions of experimental animals have been conducted by using the model of a long cold and heat action with appropriate climatic chambers. It was established experimentally that in doses of 150-300 mg/kg daily of the studied mixture has a strong antioxidant effect in the conditions of cold and heat stress on warm-blooded organism. The research allows to recommend a mixture of HP and RR as а regulator of adaptive reactions of the organism when exposed to low and high temperatures.


1998 ◽  
Vol 44 (3) ◽  
pp. 35-37 ◽  
Author(s):  
P. K. Telushkin

The rate of accumulation of malonic dialdehyde was increased, the activities of superoxide dismutase, NADP-dependent glucose- 6-phosphate, malate, isocitrate dehydrogenases and glutathione reductase decreased, and the levels of diene conjugates decreased in the hemispheres and brain stem of rats subjected to 7-9 hypoglycemic comas. The activities of neutral and acid proteases were increased in the stem structures. The detected changes indicate an oxidative stress developing in the nerve tissue after repeated hypoglycemic exposures. Such changes appear after glucose arrest of hypoglycemic coma and can be important in the pathogenesis of posthypoglycemic encephalopathy.


2003 ◽  
Vol 14 (10) ◽  
pp. 606-613 ◽  
Author(s):  
Concepción Sánchez-Moreno ◽  
Manuel Paniagua ◽  
Antonio Madrid ◽  
Antonio Martín

2013 ◽  
Vol 4 (5) ◽  
pp. 763 ◽  
Author(s):  
Yuan Yuan ◽  
Si-Jia Wu ◽  
Xin Liu ◽  
Lu-Lu Zhang

2021 ◽  
Vol 90 (1) ◽  
pp. 21-32
Author(s):  
O.M. Kovalyova ◽  
T.M. Pasiieshvili

The article is devoted to the antioxidant system of the human body in the context of biological and medical significance. The classification of antioxidants in terms of their physical and chemical properties, bioorganic compounds, biochemical effects, mechanisms of implementation of antioxidant protection is presented. The given processes of extreme radical oxidation and mechanisms of antioxidant defense in physiological and pathological conditions. The characteristics of the components of the glutathione system, namely glutathione and enzymes – glutathione peroxidase, glutathione reductase and glutathione transferase are presented. Much attention is paid to manganese superoxide dismutase, an antiradical defense enzyme, as a fundamental regulator of cell proliferation, a mediator of metabolism and apoptosis. Interpretation of changes in the antioxidant enzyme of mitochondrial origin from a prognostic point of view is interpreted on the basis of the results of clinical observations carried out by scientists in various human diseases. The expediency of determining manganese superoxide dismutase in clinical practice for the diagnostic search for the direction of the pathological process, the timely detection of complications and the appointment of adequate therapy is emphasized. Keywords: antioxidant system, classification, glutathione system, manganese superoxide dismutase.


2021 ◽  
Vol 20 (3) ◽  
pp. 70-76
Author(s):  
V. V. Zinchuk ◽  
E. S. Biletskaya

Introduction. Ozone is a physiological factor that can change hemoglobin oxygen affinity and the formation of gaseous transmitters (NO, H2S). The aim is to study the effect of ozone with gaseous transmitters donors on oxygen-dependent processes in the blood under hypoxic conditions in vitro. Materials and methods. Blood samples were divided into 6 groups of 3 ml each. Groups 2, 4, 5, 6 were pretreated with a deoxygenating gas mixture (5.5 % CO2; 94.5 % N2). In groups 3, 4, 5, 6, ozonized isotonic sodium chloride solution (with an ozone concentration of 6 mg/l) was added, and in groups 5 and 6, the donors of gas transmitters nitroglycerin and sodium hydrosulfide, respectively, were additionally introduced. Results. Pre-deoxygenation reduces the effect of ozone on oxygen transport in the blood. Nitroglycerin prevents this effect. The action of ozone under hypoxic conditions leads to an increase of content of NO3-/NO2- and H2S, and combination with nitroglycerin and sodium hydrosulfide increase these parameters. Deoxygenation due to ozone reduces parameters of lipid peroxidation (malonic dialdehyde, diene conjugates), retinol and α-tocopherol, and the same result in the nitroglycerin group. Conclusion. Under hypoxic conditions, a decrease in the effect of ozone on oxygen-dependent processes is reported. Nitroglycerin reduces its manifestation, while sodium hydrosulfide does not have a similar effect.


1995 ◽  
Vol 42 (1) ◽  
pp. 69-74 ◽  
Author(s):  
M V Borisiuk ◽  
V V Zinchuk

Endogenous hyperthermia was induced in rabbits by i.v. pyrogenal administration. Hemoglobin-oxygen affinity and parameters of free radical lipid oxidation in plasma and red blood cells were measured. The content of diene conjugates, malonic dialdehyde and Schiff bases were determined at a pyrogenal dose of 4 minimal pyrogenic doses/kg, and iron-initiated chemiluminescence, catalase activity and alpha-tocopherol concentration were determined at 6 minimal pyrogenic doses/kg. A rightward shift of the real oxyhemoglobin dissociation curve and activation of lipid peroxidation were observed. Relationships between the parameters measured were analyzed. Decreased hemoglobin-oxygen affinity is considered to be a possible mechanism of activation of free radicals during fever.


Author(s):  
Я.Г. Разуваева ◽  
А.А. Торопова ◽  
Д.Э. Гармаев

Cimicifuga dahurica - многолетнее растение семейства Ranunculaceae. В тибетской медицине С. dahurica входит в состав сборов, применяющихся при болезнях «гза» («болезни, насылаемые духами»: при инсультах, параличах и других нарушениях функций нервной системы). В середине ХХ века настойку С. dahurica использовали для лечения гипертонической болезни. С. dahurica оказывает седативное действие, ограничивая двигательную, ориентировочно-исследовательскую активность и рефлекторную возбудимость животных, а также увеличивая продолжительность наркотического сна. Цель исследования - оценка стресс-протективного действия настойки С. dahurica при хроническом эмоциональном стрессе. Методика. Исследования проведены на крысах Wistar. Длительный эмоциональный стресс воспроизводили четырехдневной иммобилизацией животных в пластмассовых пеналах с одновременным погружением их в воду. Настойку С. dahurica вводили животным (0,5 мл/кг) в течение 7 сут до моделирования эмоционального стресса и ежедневно перед помещением их в пеналы. Определяли выраженность триады Селье, уровень адренокортикотропного гормона кортикостерона и катехоламинов в плазме крови, содержание малонового диальдегида, и активность каталазы в сыворотке крови, а также активность супероксиддусмутазы в эритроцитах. Результаты. Установлено, что настойка C. dahurica повышает устойчивость животных к длительному эмоциональному стрессу, ограничивая инволюцию иммунокомпетентных органов - тимуса и селезенки на 22% и 24%, соответственно. Выраженность гипертрофии надпочечников снижалась на 34%, уменьшалось развитие язвенных повреждений слизистой оболочки желудка, что может быть связано с торможением функции симпатоадреналовой и гипоталамо-гипофизарно-адренокортикальной систем, ингибированием свободнорадикальных процессов с одновременной активацией эндогенных антиоксидантных систем. Исследуемое фитосредство ингибировало гиперактивацию перекисного окисления липидов, снижая уровень малонового диальдегида на 24%, а также повышало активность эндогенной антиоксидантной системы, увеличивая активность каталазы и супероксиддисмутазы в 1,6 и 1,3 раза соответственно. Заключение. Настойка С. dahurica в дозе 0,5 мл/кг при длительном эмоциональном стрессе оказывает стресс-протективное действие, уменьшая выраженность стресс-индуцированных изменений, ограничивая гиперактивацию центральных стресс-реализующих систем, коррегируя эндогенную антиоксидантную систему организма. Выявленный стресс-протективный эффект исследуемого фитосредства обусловлен содержанием в его составе комплекса биологически активных веществ, таких как фенольные соединения, сапонины. Cimicifuga dahurica (Turcz.) Maxim. is a perennial plant of the Ranunculaceae family. In Tibetan medicine, C. dahurica is included into medicinal collections used for the treatment of gza diseases (diseases “inflicted by demons”), such as stroke, palsies, and other functional disorders of the nervous system. In mid-20th century, the C. dahurica tincture was used for the treatment of hypertension. The C. dahurica tincture has a sedative effect; it limits motility, exploratory activity, and reflex excitability in animals and prolongs the narcotic sleep. The aim of this study was to evaluate the stress-protective effect of C. dahurica tincture in chronic emotional stress. Methods. Experiments were performed on Wistar rats weighing 180-200 g. Chronic emotional stress was produced by four-day restraint of animals in plastic cases with simultaneous water immersion. The C. dahurica tincture was administered to animals at a dose of 0.5 ml/kg for 7 days, once a day; the last dose was administered 30 min prior to testing. The following parameters were determined: intensity of the Selye’s triad, plasma concentrations of ACTH, corticosterone, and catecholamines; serum concentration of malonic dialdehyde; serum activity of catalase; and superoxide dismutase activity in red blood cells. Results. The C. dahurica tincture increased the tolerance to chronic emotional stress and restricted involution of immune-competent organs, the thymus and spleen, by 22% and 24%, respectively (p<0.05), adrenal gland hypertrophy by 34% (p<0.05), and development of stress-induced stomach ulcers. These effects could be due to inhibition of the sympathoadrenal system and the hypothalamic-pituitary-adrenocortical axis, inhibition of free-radical processes, and simultaneous activation of endogenic antioxidant systems. The C. dahurica tincture inhibited lipid peroxidation processes thus reducing the content of malonic dialdehyde by 24%. Also, the tincture potentiated the endogenous antioxidant system by increasing activities of catalase and superoxide dismutase 1.6 and 1.3 times, respectively. Conclusion. The stress-protective effect of the plant remedy is due to contained bioactive substances, such as phenolic compounds and saponins.


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