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.

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.

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

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.

scholarly journals Ethyl-acetate fraction of Trichilia catigua protects against oxidative stress and neuroinflammation after cerebral ischemia/reperfusion

2018 ◽  
Vol 221 ◽  
pp. 109-118 ◽  
Author(s):  
Jacqueline Godinho ◽  
Anacharis Babeto de Sa-Nakanishi ◽  
Lucas Stafuza Moreira ◽  
Rúbia Maria Weffort de Oliveira ◽  
Claudia Hitomi Huzita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Ethyl Acetate ◽  
Ischemia Reperfusion ◽  
Ethyl Acetate Fraction ◽  
Cerebral Ischemia Reperfusion

Effects of Normobaric Hyperoxia in a Rat Model of Focal Cerebral Ischemia—Reperfusion

2002 ◽  
Vol 22 (7) ◽  
pp. 861-868 ◽  
Author(s):  
Aneesh B. Singhal ◽  
Xiaoying Wang ◽  
Toshihisa Sumii ◽  
Tatsuro Mori ◽  
Eng H. Lo
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Protein Carbonyl ◽  
Blue Dye ◽  
Heme Oxygenase 1 ◽  
Normobaric Hyperoxia ◽  
Cerebral Ischemia Reperfusion ◽  
Carbonyl Formation

Recent studies suggest that normobaric hyperoxia can be beneficial, if administered during transient stroke. However, increased oxygenation theoretically may increase oxygen free-radical injury, particularly during reperfusion. In the present study, the authors assessed the benefit and risks of hyperoxia during focal cerebral ischemia and reperfusion. Rats were subjected to hyperoxia (Fio2 100%) or normoxia (Fio2 30%) during 2-hour filament occlusion and 1-hour reperfusion of the middle cerebral artery. At 24 hours, the hyperoxia group showed 70% (total) and 92% (cortical) reduction in infarct volumes as compared to the normoxia group. Levels of oxidative stress were evaluated using three indirect methods. First, since oxygen free radicals increase blood—brain barrier (BBB) damage, Evan's blue dye extravasation was quantified to assess BBB damage. Second, the expression of heme oxygenase-1 (HO-1), a heat shock protein inducible by oxidative stress, was assessed using Western blot techniques. Third, an immunoblot technique (“OxyBlot”) was used to assess levels of protein carbonyl formation as a marker of oxidative stress—induced protein denaturation. At 24 hours, Evan's blue dye extravasation per average lesion volume was similar between groups. There were no significant differences in HO-1 induction and protein carbonyl formation between groups, in the ipsilateral or contralateral hemispheres, at 6 hours and at 24 hours. These results indicate that hyperoxia treatment during focal cerebral ischemia—reperfusion is neuroprotective, and does not increase oxidative stress.

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