scholarly journals Platelet Mitochondrial Bioenergetics Reprogramming in Patients with Urothelial Carcinoma

2021 ◽  
Vol 23 (1) ◽  
pp. 388
Author(s):  
Patrik Palacka ◽  
Anna Gvozdjáková ◽  
Zuzana Rausová ◽  
Jarmila Kucharská ◽  
Ján Slopovský ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Urothelial Carcinoma ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Cell Metabolism ◽  
Thiobarbituric Acid ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Bioenergetics ◽  
Coq10 Level ◽  
Reverse Electron Transport

Mitochondrial bioenergetics reprogramming is an essential response of cells to stress. Platelets, an accessible source of mitochondria, have a crucial role in cancer development; however, the platelet mitochondrial function has not been studied in urothelial carcinoma (UC) patients. A total of 15 patients with UC and 15 healthy controls were included in the study. Parameters of platelet mitochondrial respiration were evaluated using the high-resolution respirometry method, and the selected antioxidant levels were determined by HPLC. In addition, oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS) concentration in plasma. We demonstrated deficient platelet mitochondrial respiratory chain functions, oxidative phosphorylation (OXPHOS), and electron transfer (ET) capacity with complex I (CI)-linked substrates, and reduced the endogenous platelet coenzyme Q10 (CoQ10) concentration in UC patients. The activity of citrate synthase was decreased in UC patients vs. controls (p = 0.0191). γ-tocopherol, α-tocopherol in platelets, and β-carotene in plasma were significantly lower in UC patients (p = 0.0019; p = 0.02; p = 0.0387, respectively), whereas the plasma concentration of TBARS was increased (p = 0.0022) vs. controls. The changes in platelet mitochondrial bioenergetics are consistent with cell metabolism reprogramming in UC patients. We suppose that increased oxidative stress, decreased OXPHOS, and a reduced platelet endogenous CoQ10 level can contribute to the reprogramming of platelet mitochondrial OXPHOS toward the activation of glycolysis. The impaired mitochondrial function can contribute to increased oxidative stress by triggering the reverse electron transport from the CoQ10 cycle (Q-junction) to CI.

scholarly journals 4- hydroxy-3,5-di-tret-butyl cinnamic acid restores the activity of the hippocampal mitochondria in rats under permanent focal cerebral ischemia

2021 ◽  
Author(s):  
Dmitry Pozdnyakov
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Respiratory Chain ◽  
Cinnamic Acid ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Mitochondrial Respiratory Chain ◽  
Respiratory Chain Complexes ◽  
Chain Complexes

Background and Purpose: Ischemic stroke remains one of the leading causes of death in the population. In addition, mitochondrial dysfunction is an essential part of the pathogenesis of cerebral ischemia and is a promising pharmacotherapeutic target. Experimental Approach: the work was performed on male Wistar rats, which were simulated cerebral ischemia by irreversible occlusion of the middle cerebral artery. 4-hydroxy-3,5-di-tret-butyl cinnamic acid (25 mg/kg, 50 mg/kg and 100 mg/kg) was injected intraperitoneally for 3 days after ischemia (daily). On the 4th day of the experiment, the changes of rat’s cognitive functions in the Morris water maze test, cellular respiration processes, the activity of the mitochondrial respiratory chain complexes and citrate synthase activity, the intensity of oxidative stress and apoptosis reactions were assessed. Key Results: it was found that the administration of 4-hydroxy-3,5-di-tret-butyl cinnamic acid at doses of 25 mg/kg and 50 mg/kg practically equivalently promotes the restoration of aerobic metabolism reactions and the activity of the mitochondrial respiratory chain complexes, decrease of the intensity of oxidative stress reactions and apoptosis, as well as an increase in the activity of citrate synthase. As a result, the restoration of mitochondrial function in the hippocampal cells contributed to the restoration of the animal’s spatial memory. Conclusion and Implications: a study showed that 4-hydroxy-3,5-di-tret-butyl cinnamic acid at doses of 25 mg/kg and 50 mg/kg has a neuroprotective effect on hippocampal neurons under conditions of permanent occlusion of the middle cerebral artery, realized by restoration of mitochondrial function.

scholarly journals Angiotensin receptor-mediated oxidative stress is associated with impaired cardiac redox signaling and mitochondrial function in insulin-resistant rats

2013 ◽  
Vol 305 (4) ◽  
pp. H599-H607 ◽  
Author(s):  
José Pablo Vázquez-Medina ◽  
Irina Popovich ◽  
Max A. Thorwald ◽  
Jose A. Viscarra ◽  
Ruben Rodriguez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Protein Expression ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Cellular Metabolism ◽  
Redox Signaling ◽  
Angiotensin Receptor ◽  
Long Evans

Activation of angiotensin receptor type 1 (AT1) contributes to NADPH oxidase (Nox)-derived oxidative stress during metabolic syndrome. However, the specific role of AT1 in modulating redox signaling, mitochondrial function, and oxidative stress in the heart remains more elusive. To test the hypothesis that AT1 activation increases oxidative stress while impairing redox signaling and mitochondrial function in the heart during diet-induced insulin resistance in obese animals, Otsuka Long Evans Tokushima Fatty (OLETF) rats ( n = 8/group) were treated with the AT1 blocker (ARB) olmesartan for 6 wk. Cardiac Nox2 protein expression increased 40% in OLETF compared with age-matched, lean, strain-control Long Evans Tokushima Otsuka (LETO) rats, while mRNA and protein expression of the H2O2-producing Nox4 increased 40–100%. ARB treatment prevented the increase in Nox2 without altering Nox4. ARB treatment also normalized the increased levels of protein and lipid oxidation (nitrotyrosine, 4-hydroxynonenal) and increased the redox-sensitive transcription factor Nrf2 by 30% and the activity of antioxidant enzymes (SOD, catalase, GPx) by 50–70%. Citrate synthase (CS) and succinate dehydrogenase (SDH) activities decreased 60–70%, whereas cardiac succinate levels decreased 35% in OLETF compared with LETO, suggesting that mitochondrial function in the heart is impaired during obesity-induced insulin resistance. ARB treatment normalized CS and SDH activities, as well as succinate levels, while increasing AMPK and normalizing Akt, suggesting that AT1 activation also impairs cellular metabolism in the diabetic heart. These data suggest that the cardiovascular complications associated with metabolic syndrome may result from AT1 receptor-mediated Nox2 activation leading to impaired redox signaling, mitochondrial activity, and dysregulation of cellular metabolism in the heart.

Mesenchymal stem cell-conditioned media ameliorate diabetic endothelial dysfunction by improving mitochondrial bioenergetics via the Sirt1/AMPK/PGC-1α pathway

2016 ◽  
Vol 130 (23) ◽  
pp. 2181-2198 ◽  
Author(s):  
Yujia Yuan ◽  
Meimei Shi ◽  
Lan Li ◽  
Jingping Liu ◽  
Bo Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Protein Kinase ◽  
Endothelial Dysfunction ◽  
Mesenchymal Stem Cell ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Mitochondrial Bioenergetics ◽  
Sirt1 Expression

Vasculopathy is a major complication of diabetes. Impaired mitochondrial bioenergetics and biogenesis due to oxidative stress are a critical causal factor for diabetic endothelial dysfunction. Sirt1, an NAD+-dependent enzyme, is known to play an important protective role through deacetylation of many substrates involved in oxidative phosphorylation and reactive oxygen species generation. Mesenchymal stem cell-conditioned medium (MSC-CM) has emerged as a promising cell-free therapy due to the trophic actions of mesenchymal stem cell (MSC)-secreted molecules. In the present study, we investigated the therapeutic potential of MSC-CMs in diabetic endothelial dysfunction, focusing on the Sirt1 signalling pathway and the relevance to mitochondrial function. We found that high glucose-stimulated MSC-CM attenuated several glucotoxicity-induced processes, oxidative stress and apoptosis of endothelial cells of the human umbilical vein. MSC-CM perfusion in diabetic rats ameliorated compromised aortic vasodilatation and alleviated oxidative stress in aortas. We further demonstrated that these effects were dependent on improved mitochondrial function and up-regulation of Sirt1 expression. MSC-CMs activated the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), leading to direct interaction between Akt and Sirt1, and subsequently enhanced Sirt1 expression. In addition, both MSC-CM and Sirt1 activation could increase the expression of peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), as well as increase the mRNA expression of its downstream, mitochondrial, biogenesis-related genes. This indirect regulation was mediated by activation of AMP-activated protein kinase (AMPK). Overall our findings indicated that MSC-CM had protective effects on endothelial cells, with respect to glucotoxicity, by ameliorating mitochondrial dysfunction via the PI3K/Akt/Sirt1 pathway, and Sirt1 potentiated mitochondrial biogenesis, through the Sirt1/AMPK/PGC-1α pathway.

Effect of different models of physical exercise on oxidative stress markers in mouse liver

2009 ◽  
Vol 34 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Luciano A. da Silva ◽  
Cleber A. Pinho ◽  
Luis G.C. Rocha ◽  
Talita Tuon ◽  
Paulo C.L. Silveira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Physical Exercise ◽  
Mouse Liver ◽  
Citrate Synthase ◽  
Training Session ◽  
Thiobarbituric Acid ◽  
Oxidative Stress Markers ◽  
Sod Activity ◽  
Stress Markers ◽  
Continuous Running

The aim of this study was to investigate the effect of different protocols of physical exercise on oxidative stress markers in mouse liver. Twenty-eight male CF1 mice (30–35 g) were distributed into 4 groups (n = 7) — untrained (UT), continuous running (CR), downhill running (D-HR), and intermittent running (IR) — and underwent an 8-week training program. Forty-eight hours after the last training session, the animals were killed, and their livers were removed. Blood lactate, creatine kinase, citrate synthase, thiobarbituric acid reactive species, carbonyl, superoxide dismutase (SOD), and catalase (CAT) activities were assayed. Results show a decrease in the level of lipoperoxidation and protein carbonylation in the CR and D-HR groups. SOD activity was significantly increased and CAT activity was reduced in the CR and D-HR groups. Our findings indicate that CR and D-HR may be important for decreasing oxidative damage and in the regulation of antioxidant enzymes (SOD and CAT) in the livers of trained mice.

Behavioral dysfunction, brain oxidative stress, and impaired mitochondrial electron transfer in aging mice

2002 ◽  
Vol 282 (4) ◽  
pp. R985-R992 ◽  
Author(s):  
Ana Navarro ◽  
María Jesús Sánchez Del Pino ◽  
Carmen Gómez ◽  
Juan Luis Peralta ◽  
Alberto Boveris
Keyword(s):  
Oxidative Stress ◽  
Electron Transfer ◽  
Life Span ◽  
Citrate Synthase ◽  
Thiobarbituric Acid ◽  
Cross Sectional Study ◽  
Mitochondrial Enzymes ◽  
Sod Activity ◽  
Cross Sectional ◽  
Old Mice

Behavioral tests, tightrope success, and exploratory activity in a T maze were conducted with male and female mice for 65 wk. Four groups were defined: the lower performance slow males and slow females and the higher performance fast males and fast females. Fast females showed the longest life span and the highest performance, and slow males showed the lowest performance and the shortest life span. Oxidative stress and mitochondrial electron transfer activities were determined in brain of young (28 wk), adult (52 wk), and old (72 wk) mice in a cross-sectional study. Brain thiobarbituric acid reactive substances (TBARS) were increased by 50% in old mice and were ∼15% higher in males than in females and in slow than in fast mice. Brain Cu,Zn-superoxide dismutase (SOD) activity was increased by 52% and Mn-SOD by 108% in old mice. The activities of mitochondrial enzymes NADH-cytochrome c reductase, cytochrome oxidase, and citrate synthase were decreased by 14–58% in old animals. The cumulative toxic effects of oxyradicals are considered the molecular mechanism of the behavioral deficits observed on aging.

P0851THE DIFFERENTIAL IMPACT OF INTRAVENOUS IRON IN A MODEL OF EXPERIMENTAL URAEMIA ON TISSUE MARKERS OF OXIDATIVE STRESS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sunil Bhandari ◽  
Faisal Nuhu ◽  
Anne Marie Seymour
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Cardiac Tissue ◽  
Intravenous Iron ◽  
Thiobarbituric Acid ◽  
Iron Therapy ◽  
Sprague Dawley ◽  
Post Surgery ◽  
Parenteral Iron ◽  
The Impact

Abstract Background and Aims Uraemia leads to changes in cardiac structure, metabolic remodelling and anaemia, key factors in the development of heart failure in patients with chronic kidney disease (CKD). Previous studies have identified abnormalities in mitochondrial function in experimental uraemia, potentially impairing energy provision and enhancing oxidative stress. The aim of this study was to characterise oxidant status and changes in mitochondrial function in uraemia and the impact of iron therapy. Method Experimental uraemia was induced in male Sprague-Dawley rats via a subtotal nephrectomy and parenteral iron administration at 6 weeks post-surgery (10mg/Kg body weight). Pro-oxidant activities and antioxidant capacities (oxidised glutathione (GSSG) relative to reduced (GSH)) in both sham and uraemic animals and lipid peroxidation (thiobarbituric acid-reactive substances (TBARS) was measured. Mitochondrial function was assessed using the SEAHORSE analyser. Results Oxidative stress was increased in cardiac tissue (69% increase in GSSG/GSH ratio, 38% rise in TBARS and significantly (79%) upregulated NADPH oxidase activity. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities were significantly increased by 30%. Iron reduced GSSG/GSH ratio and TBARS by 62% and 51% respectively. Iron therapy was also associated with significantly increased aconitase activity. Parenteral iron improved respiratory reserve in cardiac mitochondria and skeletal mitochondria suggests IV iron restores mitochondrial function. Conclusion Uraemia leads or oxidative stress and mitochondrial dysfunction in cardiac tissue. Iron therapy reduces oxidative stress and improves cardiac mitochondrial function. This might lead to reduced adverse cardiovascular outcomes in CKD.

Resistance of erythrocytes from Brown trout (Salmo trutta m. trutta L.) affected by ulcerative dermal necrosis syndrome

2011 ◽  
Vol 14 (3) ◽  
pp. 443-448 ◽  
Author(s):  
N. Kurhalyuk ◽  
H. Tkachenko ◽  
K. Pałczyńska
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Brown Trout ◽  
Salmo Trutta ◽  
Thiobarbituric Acid ◽  
Control Group ◽  
Thiobarbituric Acid Reactive Substance ◽  
Tbars Level ◽  
Reactive Substance ◽  
Brown Trout Salmo Trutta

Resistance of erythrocytes from Brown trout (Salmo trutta m. trutta L.) affected by ulcerative dermal necrosis syndrome In the present work we evaluated the effect of ulcerative dermal necrosis (UDN) syndrome on resistance of erythrocytes to haemolytic agents and lipid peroxidation level in the blood from brown trout (Salmo trutta m. trutta L.). Results showed that lipid peroxidation increased in erythrocytes, as evidenced by high thiobarbituric acid reactive substance (TBARS) levels. Compared to control group, the resistance of erythrocytes to haemolytic agents was significantly lower in UDN-positive fish. Besides, UDN increased the percent of hemolysated erythrocytes subjected to the hydrochloric acid, urea and hydrogen peroxide. Results showed that UDN led to an oxidative stress in erythrocytes able to induce enhanced lipid peroxidation level, as suggested by TBARS level and decrease of erythrocytes resistance to haemolytic agents.

Association Between Magnesium and Oxidative Stress in Patients with Obesity

2020 ◽  
Vol 16 (5) ◽  
pp. 743-748
Author(s):  
Ana R.S. de Oliveira ◽  
Kyria J.C. Cruz ◽  
Jennifer B.S. Morais ◽  
Juliana S. Severo ◽  
Jéssica B. Beserra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Thiobarbituric Acid ◽  
Magnesium Concentration ◽  
Control Group ◽  
Compensatory Mechanism ◽  
Thiobarbituric Acid Reactive Substances ◽  
Magnesium Intake ◽  
Significant Difference ◽  
Dietary Magnesium ◽  
And Control

Background: The role of minerals in preventing the generation of oxidative stress in obese individuals has been evaluated. Magnesium is an antioxidant nutrient and a cofactor of enzymes involved in the cell membrane stabilization, attenuating the effects of oxidative stress. Objective: To evaluate the association between magnesium and concentrations of thiobarbituric acid reactive substances (TBARS) in patients with obesity and eutrophic women. Methods: A cross-sectional study was conducted with 73 women, divided into two groups: case group (patients with obesity, n=27) and control group (eutrophic women, n=46). Measurements of body mass index and waist circumference were performed. Dietary magnesium intake was assessed by the three-day food record using the NutWin software. Urinary magnesium concentration was measured by atomic absorption spectrophotometry method. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were also determined. Results: Mean values of dietary magnesium intake were 161.59 ± 60.04 and 158.73 ± 31.96 for patients with obesity and control group, respectively, with no significant difference between the groups studied (p >0.05). The value of urinary excretion of magnesium was lower than the reference values in both groups, with no significant difference between the groups studied (p >0.05). The plasma concentration of thiobarbituric acid reactive substances was significantly higher in patients with obesity compared to the control group (p <0.001). There was no correlation between levels of magnesium biomarkers and the concentration of TBARS (p >0.05). Conclusion: Patients with obesity showed a reduced dietary magnesium intake which seems to induce hypomagnesuria as a compensatory mechanism. The marker of oxidative stress evaluated in this study was not influenced by magnesium.

Role of Quercetin in Mitigation of Lindane Induced Toxicity in Terms of Oxidative Responses and Metabolic Status in Mice Brain

2020 ◽  
Vol 16 ◽  
Author(s):  
Anupama Sharma ◽  
Renu Bist ◽  
Hemant Pareek
Keyword(s):  
Citrate Synthase ◽  
Thiobarbituric Acid ◽  
Tca Cycle ◽  
Treated Group ◽  
Protein Carbonyl ◽  
Protein Carbonyl Content ◽  
Mice Brain ◽  
The Brain ◽  
Oxidative Responses

Background:: Current study evaluated the protective potential of quercetin against lindane induced toxicity in mice brain. For investigation, mice were allocated into four groups; First group was control. Second group was administered with oral dose of lindane (25 mg/kg bw) for 4 consecutive days. Third group was exposed to quercetin (40 mg/kg bw) and in fourth group, quercetin was administered 1 hour prior to the exposure of lindane. Objective:: Two major objectives were decided for study. First was to create lesions in the brain by lindane and; second was to evaluate the neuroprotective potential of quercetin. Methods:: To study oxidative responses, level of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), reduced glutathione (GSH), superoxide dismutase (SOD), Catalase (CAT), and glutathione peroxidase (GPx) were measured in brain homogenates. Three key step regulating enzymes of tricarboxylic acid (TCA) cycle viz citrate synthase (CS), pyruvate dehydrogenase (PDH) and fumarase were also assayed. Results:: Lindane treatment significantly enhanced the levels of TBARS (P<0.001),PCC (P<0.001), GPx (P<0.001), SOD (P<0.05), PDH (P<0.05) and fumarase (P<0.001) in brains of mice compared to control. Meanwhile, it alleviated GSH, CAT and CS (P<0.05) activity. Conclusion:: Pretreatment with quercetin in lindane treated group not only restored, previously altered biochemical parameters after lindane treatment and also significantly improved them too which suggests that quercetin is not only invulnerable rather neuroprotective against lindane intoxication.

scholarly journals Antioxidant Activity of the Isoflavonoids from the Roots of Maackia amurensis

2013 ◽  
Vol 8 (5) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Nadezda I. Kulesh ◽  
Sergey A. Fedoreyev ◽  
Marina V. Veselova ◽  
Natalia P. Mischenko ◽  
Vladimir A. Denisenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Glutathione Peroxidase ◽  
Column Chromatography ◽  
Thiobarbituric Acid ◽  
Formalin Injection ◽  
Thiobarbituric Acid Reactive Substances ◽  
H Nmr ◽  
Maackia Amurensis

Seven isoflavonoids, including a new glycoside, (6a R,11a R)-medicarpin-3- O-gentiobioside (6), were isolated from the roots of Maackia amurensis using repeated column chromatography on a Toyopearl HW-50F sorbent and identified by HPLC–PDA–MS, 1H NMR, 13C, 1H–1H COSY, HSQC NMR and HMBC NMR analyses as daidzin (1), genistein-7- O-gentiobioside (2), pseudobaptigenin-7- O-gentiobioside (3), formononetin-7- O-gentiobioside (4), (6a R,11a R)-maackiain-3- O-gentiobioside (5), and 5- O-methylgenistein-7- O-gentiobioside (7). In the model of oxidative stress induced by formalin injection, the isolated isoflavone and pterocarpan glucosides 1-7 were shown to reduce the formation of malondialdehyde (MDA) and other thiobarbituric acid reactive substances (TBARS), as well as glutathione peroxidase (GPO) activity in rats.

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