Abstract 361: The Augmentation of Oxygen-sensitive Generation of Oxygen Radicals in Mitochondria and the Attenuation of Hyperoxia-induced Oxidative Stress After Cardiac Arrest

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Koichiro Shinozaki ◽  
Yu Okuma ◽  
Tomoaki Aoki ◽  
Mitsuaki Nishikimi ◽  
Kei Hayashida ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Ex Vivo ◽  
Lung Injury Score ◽  
Ros Generation ◽  
Absolute Change ◽  
Isolated Mitochondria ◽  
Carbonyl Protein ◽  
Oxygen Sensitive ◽  
The Brain

Introduction: Hyperoxia can induce oxidative stress resulting in organ injuries after cardiac arrest (CA). Mitochondrial reactive oxygen species (ROS) are key to understanding its mechanism, however the augmentation of oxygen-sensitive ROS generation caused by CA ( Fig 1 ) has not been well described. Methods: Rats were assigned into: 1) sham with normoxia, 30% O2; 2) sham with hyperoxia, 100% O2; 3) CA with normoxia; and 4) CA with hyperoxia (n=15 for each group). CA was induced by 10-minute asphyxia and CPR was delivered. Neurological deficit score (NDS), histological lung injury score (LIS), survival time were obtained from the CA groups. Carbonyl protein as an oxidative stress indicator was measured at 2 hrs after resuscitation. H2O2 generation from isolated mitochondria were measured ex vivo at a normoxic and hyperoxic condition set up with nitrogen and air saturated medium. Results: Between the CA groups, the normoxia group had a higher 48hr-survival rate (77%), lower NDS (359±140), and lower LIS (4.3±2.9) compared to those (28%, 452±85, 14±2, respectively) of the hyperoxia group (p<0.01, p<0.05, and p<0.01, respectively). In the brain, lung, and kidney, CA augmented the hyperoxia-induced increase in carbonyl protein (absolute change: sham brain, 0.18 nmol/mg protein vs. CA brain, 0.61 nmol/mg protein; sham lung, 0.29 nmol/mg protein vs. CA lung, 0.72 nmol/mg protein; sham kidney, 0.04 nmol/mg protein vs. CA kidney, 0.55 nmol/mg protein, respectively). In the brain and kidney isolated mitochondria, CA augmented the hyperoxia-induced increase in H2O2 (absolute change: sham brain, 18 pmol/mg protein vs. CA brain, 60 pmol/mg protein; sham kidney, 16 pmol/mg protein vs. CA kidney, 45 pmol/mg protein, respectively). Conclusions: The normoxic therapy may attenuate organ damage and improve survival of CA. The reduction of augmented mitochondrial ROS generation, which is oxygen-sensitive, would be an important mechanism and therapeutic target of post-CA care.

scholarly journals Detecting Validated Intracellular ROS Generation with 18F-dihydroethidine-Based PET

2021 ◽  
Author(s):  
Edward C. T. Waters ◽  
Friedrich Baark ◽  
Zilin Yu ◽  
Filipa Mota ◽  
Thomas R. Eykyn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Contractile Function ◽  
Ex Vivo ◽  
Glutathione Depletion ◽  
Ros Generation ◽  
Cardiac Contractile ◽  
Rat Hearts ◽  
Intracellular Ros ◽  
Cardiac Contractile Dysfunction

Abstract Purpose To determine the sensitivity of the 18F-radiolabelled dihydroethidine analogue ([18F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress. Procedures The sensitivity of [18F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [18F]DHE (50–150 kBq.min−1) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress. Results [18F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [18F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation. Conclusion [18F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.

Abstract 219: Supplement Oxygen Dependence of Dissociated Oxygen Metabolism From Carbon Dioxide and Oxidative Toxic Stress in Post-Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Yu Okuma ◽  
Koichiro Shinozaki ◽  
Mitsuaki Nishikimi ◽  
Kota Saeki ◽  
Tai Yin ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Cardiac Arrest ◽  
Sham Group ◽  
Oxygen Metabolism ◽  
Supplemental Oxygen ◽  
Ros Generation ◽  
Toxic Stress ◽  
Tissue Samples ◽  
Carbonyl Protein ◽  
Cellular Dna

Objective: We recently reported a dissociation of oxygen metabolism in post-cardiac arrest rodents, which was represented by an increase in oxygen consumption (VO 2 ) without a concomitant increase in carbon dioxide generation (VCO 2 ) resulting in a lowered respiratory quotient (RQ) outside of the normally cited range of 0.7-1.0. We hypothesize that high supplemental O 2 is associated with both increased dissociation of oxygen metabolism and oxidative toxic stress after cardiac arrest (CA). Methods: Rats were resuscitated from 10 minutes of asphyxial CA and stratified into 2 groups: those that inhaled 100% supplemental O 2 (CA-FIO2 1.0) and those that inhaled 30% supplemental O 2 (CA-FIO2 0.3). We prepared a sham surgery group for comparison (sham-FIO2 0.3). Our newly developed method enabled measurements of VO 2 and VCO 2 from low to high inspiratory supplemental O 2 levels. RQ was calculated as VCO 2 /VO 2 . After 2 hours, we collected urine and tissue samples to determine the degree of reactive oxygen species (ROS) generation. Results: CA increased VO 2 (28.5±8.1 mL/kg/min at FIO2 1.0 and 19.1±3.0 at FIO2 0.3, p<0.05) compared with the sham group (15.0±1.4), whereas no differences in VCO 2 were found among the three groups. RQ of CA-FIO2 1.0 animals persistently decreased to 0.57±0.03 (0.84 ±0.10 at CA-FIO2 0.3 and 0.96±0.14 at sham-FIO2 0.3). Regarding ROS generation, urinary 8-hydroxydeoxyguanosine (8-OHdG) and brain carbonyl protein of CA-FIO2 1.0 animals was significantly higher than the CA-FIO2 0.3 or sham groups. Conclusions: 100% supplemental oxygen increased VO 2 but not VCO 2 . 8-OHdG is produced during the repair of cellular DNA damaged from oxidative toxic stress and excreted into the urine. Our findings suggest that the high supplemental oxygen aggravate both dissociation of oxygen metabolism and oxidative toxic stress in post-CA rodents.

Abstract 12423: Normoxic Therapy Attenuated Oxidative Stress Related mRNA Gene Expressions in a Post-Cardiac Arrest Rat Model

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Tomoaki Aoki ◽  
Koichiro Shinozaki ◽  
Yu Okuma ◽  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cardiac Arrest ◽  
Signaling Pathways ◽  
Expression Patterns ◽  
Expression Levels ◽  
Mrna Gene ◽  
The Brain ◽  
Mrna Gene Expression ◽  
Gene Expression Levels

Objective: We recently reported that post-resuscitation normoxic therapy attenuates oxidative stress in multiple organs and improves post-cardiac arrest (CA) organ injury, oxygen metabolism, and survival. Yet, detailed mechanisms of gene expression patterns and signaling pathways mitigated by normoxic therapy have not been elucidated. Therefore, we assessed post-resuscitation normoxic therapy-modified gene expression of oxidative stress-related signaling molecules. Methods: Rats were resuscitated from 10 minutes of asphyxial CA and divided into 2 groups: those that inhaled 100% supplemental O 2 (CA-FIO2 1.0) and those that inhaled 30% supplemental O 2 (CA-FIO2 0.3). Control groups were also prepared for comparison (control-FIO2 1.0, control-FIO2 0.3). At 2 hours after resuscitation, brain and heart tissues were collected, and mRNA purifications followed by real-time PCR measurements were performed to compare gene expression of hyperoxia-induced inflammatory and apoptosis-related signaling pathways amongst these groups. Results: In the brain, relative IL-1 beta mRNA gene expression levels, which represent inflammatory signaling pathways, increased post-CA (8.1±2.3 in CA-FIO2 1.0 and 1.0±0.4 in control-FIO2 0.3, p<0.05), but were significantly attenuated by normoxic therapy (2.3±0.2 in CA-FIO2 0.3, p<0.05). Likewise, normoxic therapy significantly reduced oxidative stress-induced inflammatory (NFKB1, TGFB1, MAPK14, TRAF6) and apoptosis-related (BAX, EGF) mRNA gene expression levels in the brain, whereas no statistical differences were detected in the heart. Conclusions: Post-CA normoxic therapy significantly attenuated the gene expression of oxidative stress-induced inflammation and apoptosis in the brain, while there were no remarkable changes in the heart. Therefore, it is inferred that the heart is more tolerant to hyperoxic injury compared to the brain.

Effect of Achyranthes Aspera Linn. Leaves Extract on Reactive Oxygen Species (ROS) in Diabetes induced Rat by Flow cytometry and Possible Molecular Mechanism through Molecular Docking

2020 ◽  
Vol 16 ◽  
Author(s):  
Trupti C. Deshpande ◽  
Hemant D. Une
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Flow Cytometry ◽  
Molecular Docking ◽  
Oral Dose ◽  
Ethyl Acetate ◽  
Ethyl Acetate Extract ◽  
Ros Generation ◽  
Oxygen Species ◽  
The Brain

Background:: Oxidative stress is caused due to the overproduction of the reactive oxygen species (ROS) and the disturbance developed in the antioxidant potential of biochemical processes. ROS mostly formed in the brain due to the high consumption of oxygen and the insufficiency of endogenous antioxidant resistance mechanisms. Cytochrome P450 2E1 has an excessive percentage of NADPH oxidase activity, which causes the production of ROS and increases oxidative stress. Objectives:: We have studied the effect of Ethyl Acetate Extract of Achyrantes Aspera (EAAA) on ROS in the brain of diabetes-induced rats. We have also investigated the possible molecular mechanism of reduction in ROS through molecular docking. Methods: To study the oxidative stress induced by ROS in diabetic rats, we have estimated the ROS in rat brain through Flow cytometry. The oral dose of EAAA 50mg/kg and 100 mg/kg were given to diabetes induces rats. Results were articulated as mean ± standard deviation (SD). Data were analyzed using analysis of variance (ANOVA) followed by Bonferroni as a post hoc test. We have performed molecular docking of flavonoids on CYP2E1 to study the inhibitory potential. Results:: The results have shown that EAAA reduces the generation of ROS in the diabetes-induced rat in a dose-dependent manner. The oral dose of EAAA 50mg/kg and 100 mg/kg was given to the rat and the ROS generation got affected accordingly. Luteolin, Quercetin, and Apigenin have inhibited the CYP2E1 very effectively. Luteolin has formed 4 hydrogen bonds with CYP2E1 which indicate its potential inhibition. Although, Luteolin and Apigenin have shown a very good binding affinity with the enzyme. Conclusion:: From the present work we have concluded that the Ethyl Acetate Extract of Achyrantesaspera can effectively inhibit the ROS generation in the diabetes-induced rats by inhibiting the activity of CYP2E1.

scholarly journals Astragaloside IV Attenuates Myocardial Ischemia-Reperfusion Injury from Oxidative Stress by Regulating Succinate, Lysophospholipid Metabolism, and ROS Scavenging System

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Miaomiao Jiang ◽  
Jingyu Ni ◽  
Yuanlin Cao ◽  
Xiaoxue Xing ◽  
Qian Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Ros Scavenging ◽  
Astragaloside Iv ◽  
Wide Range

Astragaloside IV is one of the main active ingredients isolated from Astragalus membranaceus. Here we confirmed its protective effect against cardiac ischemia-reperfusion (I/R) injury and aimed to investigate the potential molecular mechanisms involved. Pretreatment of ex vivo and in vivo I/R-induced rat models by astragaloside IV significantly prevented the ratio of myocardium infarct size, systolic and diastolic dysfunction, and the production of creatine kinase and lactate dehydrogenase. Metabolic analyses showed that I/R injury caused a notable reduction of succinate and elevation of lysophospholipids, indicating excessive reactive oxygen species (ROS) generation driven by succinate’s rapid reoxidization and glycerophospholipid degradation. Molecular validation mechanistically revealed that astragaloside IV stimulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) released from Kelch-like ECH-associated protein 1 (Keap1) and translocated to the nucleus to combine with musculoaponeurotic fibrosarcoma (Maf) to initiate the transcription of antioxidative gene heme oxygenase-1 (HO-1), which performed a wide range of ROS scavenging processes against pathological oxidative stress in the hearts. As expected, increasing succinate and decreasing lysophospholipid levels were observed in the astragaloside IV-pretreated group compared with the I/R model group. These results suggested that astragaloside IV ameliorated myocardial I/R injury by modulating succinate and lysophospholipid metabolism and scavenging ROS via the Nrf2 signal pathway.

scholarly journals Effects of Post‐Resuscitation Normoxic Therapy on Oxygen‐Sensitive Oxidative Stress in a Rat Model of Cardiac Arrest

2021 ◽  
Author(s):  
Yu Okuma ◽  
Lance B. Becker ◽  
Kei Hayashida ◽  
Tomoaki Aoki ◽  
Kota Saeki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cardiac Arrest ◽  
Weight Ratio ◽  
Reactive Oxygen ◽  
Oxygen Metabolism ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Multiple Organs ◽  
Oxygen Sensitive

Background Cardiac arrest (CA) can induce oxidative stress after resuscitation, which causes cellular and organ damage. We hypothesized that post‐resuscitation normoxic therapy would protect organs against oxidative stress and improve oxygen metabolism and survival. We tested the oxygen‐sensitive reactive oxygen species from mitochondria to determine the association with hyperoxia‐induced oxidative stress. Methods and Results Sprague–Dawley rats were subjected to 10‐minute asphyxia‐induced CA with a fraction of inspired O 2 of 0.3 or 1.0 (normoxia versus hyperoxia, respectively) after resuscitation. The survival rate at 48 hours was higher in the normoxia group than in the hyperoxia group (77% versus 28%, P <0.01), and normoxia gave a lower neurological deficit score (359±140 versus 452±85, P <0.05) and wet to dry weight ratio (4.6±0.4 versus 5.6±0.5, P <0.01). Oxidative stress was correlated with increased oxygen levels: normoxia resulted in a significant decrease in oxidative stress across multiple organs and lower oxygen consumption resulting in normalized respiratory quotient (0.81±0.05 versus 0.58±0.03, P <0.01). After CA, mitochondrial reactive oxygen species increased by ≈2‐fold under hyperoxia. Heme oxygenase expression was also oxygen‐sensitive, but it was paradoxically low in the lung after CA. In contrast, the HMGB‐1 (high mobility group box‐1) protein was not oxygen‐sensitive and was induced by CA. Conclusions Post‐resuscitation normoxic therapy attenuated the oxidative stress in multiple organs and improved post‐CA organ injury, oxygen metabolism, and survival. Additionally, post‐CA hyperoxia increased the mitochondrial reactive oxygen species and activated the antioxidation system.

Abstract 113: Glucose Metabolic Disorders in Aging-Associated Microglial NADPH Oxidase 2 Activation and Oxidative Damage of Cerebral Microvasculature and Neurons

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Li Geng ◽  
Jian-Mei Li
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Metabolic Disorders ◽  
Aging Brain ◽  
Ros Generation ◽  
Ros Production ◽  
The Brain

Aging has been recognised to be a major risk factor for the development of cardiovascular and neurodegenerative diseases and growing evidence suggests a role for oxidative stress. A Nox2-containing NADPH oxidase has been reported to be a major source of reactive oxygen species (ROS) generation in the vascular system and in the brain. However, the role of Nox2 enzyme in aging-related metabolic disorders and vascular neurodegeneration remains unclear. In this study, we used age-matched wild-type (WT) and Nox2-deficient (Nox2 -/- ) mice on a C57BL/6 background at young (3-4 month) and aging (20-24 month) to investigate the role of Nox2 in aging-related oxidative stress, metabolic disorders and cerebral vascular dysfunction. There was an aging-related increase in blood pressure in WT mice (126 mmHg for young and 148 mmHg for aging) (P<0.05); however the blood pressure was well maintained without significant change in Nox2 -/- aging mice. Compared to young WT mice, WT aging mice had significantly high levels of fasting serum insulin and this was accompanied with delayed clearance of glucose (P<0.05) indicating insulin resistance. In contrast, there was no indication of insulin resistance for Nox2 -/- aging mice. We then examined aging-related brain oxidative stress. Compared to WT young mice, there were significant increases (2.7±0.7 folds) in the levels of ROS production by WT aging brain tissue homogenates as detected by lucigenin-chemiluminescence and DHE fluorescence. Increased ROS production in WT aging brain was accompanied by a significant increase (1.8±0.3 folds) in the Nox2 expression detected mainly in the microglial cells (labelled by Iba-1) and decreases in brain capillaries (labelled by CD31) (2.4±0.8 folds) and neurons (labelled by Neu-N) (2.9±0.5 folds) (all P<0.05). Knockout of Nox2 abolished aging-associated increases in brain ROS production and significantly reduced the aging-related pathophysiological changes in the brain. In conclusion, aging-associated metabolic disorders play a crucial role in aging-associated Nox2 activation and vascular neurodegeneration. Nox2-containing NADPH oxidase represents a valuable therapeutic target for oxidative stress-related brain microvascular damage and neurodegeneration.

Neuroprotection by tempol in a model of iron-induced oxidative stress in acute ischemic stroke

2004 ◽  
Vol 286 (2) ◽  
pp. R283-R288 ◽  
Author(s):  
Shyamal H. Mehta ◽  
R. Clinton Webb ◽  
Adviye Ergul ◽  
Amany Tawak ◽  
Anne M. Dorrance
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Brain Slices ◽  
Ros Generation ◽  
Peripheral Vasculature ◽  
Iron Citrate ◽  
The Brain

Studies suggest iron exacerbates the damage caused by ischemic stroke. Our aim was to elucidate the effect of iron overload on infarct size after middle cerebral artery occlusion (MCAO) and to evaluate the efficacy of tempol, a superoxide dismutase mimetic, as a neuroprotective agent. Rats were administered iron ± tempol before MCAO; control rats received saline. The middle cerebral artery was occluded for 24 h, and the size of the resultant infarct was assessed and expressed as the percentage of the hemisphere infracted (%HI). Iron treatment increased infarct size compared with control (51.83 ± 3.55 vs. 27.56 ± 3.28%HI iron treated vs. control, P = 0.01); pretreatment with tempol reversed this (51.83 ± 3.55 vs. 26.09 ± 9.57%HI iron treated vs. iron + tempol treated, P = 0.02). We hypothesized that reactive oxygen species (ROS) were responsible for the iron-induced damage. We measured ROS generated by exogenous iron in brain and peripheral vasculature from rats that had not undergone MCAO. There was no increase in ROS production in the brain of iron-treated rats or in brain slices incubated with iron citrate. However, ROS generation in carotid arteries incubated with iron citrate was significantly increased. ROS generation from the brain was assessed after MCAO by dihydroethidine staining; there was a dramatic increase in the ROS generation by the brain in the iron-treated rats compared with control 30 min after MCAO. We propose that iron-induced ROS generation in the cerebral vasculature adds to oxidative stress during an ischemic episode after the disruption of the blood-brain barrier.

Abstract 031: Placental Ischemia Causes Mitochondrial Dysfunction in Reduced Uterine Perfusion Pressure Rats

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Venkata Ramana Vaka ◽  
Mark W Cunningham ◽  
Tarek Ibrahim ◽  
Lorena M Amaral ◽  
Babbette LaMarca
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Mitochondrial Dysfunction ◽  
Cytochrome C Oxidase ◽  
Perfusion Pressure ◽  
Ros Generation ◽  
Complex Iv ◽  
Isolated Mitochondria ◽  
Uterine Perfusion ◽  
Placental Ischemia

Introduction: Placental ischemia is believed to be the initial event in the development of preeclampsia (PE). PE is characterized by new onset hypertension and is associated with reduced fetal weight and placental oxidative stress. Mitochondrial dysfunction is the major cause of reactive oxygen species (ROS) generation. We hypothesize that the placental ischemia causes mitochondrial dysfunction in the reduced uterine perfusion pressure (RUPP) rat model of PE. Thus, the purpose of this study is to examine the effect of placental ischemia on mitochondrial function. Methods: Female Sprague Dawley rats were dived into two groups; normal pregnant (NP) and RUPP rats. On gestational day (GD) 14, RUPP surgery was performed, GD18 carotid catheters were inserted, and GD19 conscious blood pressure (MAP) was measured. GD 19 placentas were collected and mitochondria were isolated for respiration measurements. Respiration measurements included: basal state (isolated mitochondria with no substrates), state 2 (glutamate and malate as complex I substrates), state 3 (ADP stimulated), leak state (oligomycin induced ATP synthase inhibition), and maximal state (FCCP stimulated uncoupled). Cytochrome C oxidase (complex IV) activity was also measured in isolated mitochondria. Results: MAP was elevated in RUPP (n=16) compared to NP rats (n=14) (119±2 vs. 100±2 mmHg, p<0.05). State 3 (149±8 vs 220±12 pmol/sec/mg, p<0.05) and maximal (123±8 vs 159±5 pmol/sec/mg, p<0.05) respiration rates were significantly reduced in RUPP (n=5) vs NP (n=7) rats. However, basal, state 2, and state 4 respiratory rates were not different between RUPP vs NP. Respiratory control ratio (state 3/ state 4) was significantly reduced in RUPP (n=5) vs NP (n=7) (7±1 vs 10±1, p<0.05). Complex IV activity was reduced in RUPP (n=5) vs. NP (n=6) rats (508±14 vs 644±17 nmol e-/min/mg, P<0.05). Conclusion: Reduced mitochondrial respiration and cytochrome c oxidase activity, indicators of mitochondrial dysfunction, occur in response to placental ischemia during pregnancy. Thus, suggesting that mitochondrial dysfunction may contribute to the pathophysiology of oxidative stress and hypertension during PE.

scholarly journals Chronic Variable Stress Is Responsible for Lipid and DNA Oxidative Disorders and Activation of Oxidative Stress Response Genes in the Brain of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mariola Herbet ◽  
Agnieszka Korga ◽  
Monika Gawrońska-Grzywacz ◽  
Magdalena Izdebska ◽  
Iwona Piątkowska-Chmiel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Indirect Evidence ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Ros Generation ◽  
Repair System ◽  
Stress Response Genes ◽  
Chronic Variable Stress ◽  
The Brain

Chronic environmental stress is associated with reactive oxygen species (ROS) overproduction and the pathogenesis of depression. The purpose of this study was to evaluate biochemical and molecular changes associated with ROS generation in the brains of rats submitted to chronic variable stress. Male Wistar rats (50–55 days old, weighing 200–250 g) were divided in two groups (n=10): control and stressed. Rats in the stressed group were exposed to stress conditions for 40 days. The animals were decapitated and the brain samples were collected. In prefrontal cortex, we measured the following biochemical parameters: lipid peroxidation and concentration of glutathione—GSH, GSSG, GSH/GSSG ratio, glutathione peroxidase, and glutathione reductase activities. In the hippocampus marker of DNA, oxidative damage and expression of DNA-repairing genes (Ogg1,MsrA) and gene-encoding antioxidative transcriptional factor (Nrf2) were determined. The results demonstrate indirect evidence of ROS overproduction and presence of oxidative stress. They also reveal disruption of oxidative defense systems (decreased GR activity, diminished GSH/GSSG ratio, and decreasedNrf2expression) and activation of the oxidative DNA repair system (increasedOgg1andMsrAexpression). Together, the presented data suggest that independent activation of oxidative stress response genes occurs in chronic variable stress conditions.

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