Parenteral Succinate Reduces Systemic ROS Production in Septic Rats, but It Does Not Reduce Creatinine Levels

In sepsis, reactive oxygen species (ROS) production is increased. This process takes place mainly within the electron transport chain. ROS production is part of the pathophysiology of multiple organ failure in sepsis. Succinate yields Dihydroflavine-Adenine Dinucleotide (FADH2), which enters the chain through complex II, avoiding complex I, through which electrons are lost. The aim of this work is to determine if parenteral succinate reduces systemic ROS production and improves kidney function. Rats with cecal ligation and puncture were used as model of sepsis, and 4 groups were made: Control group; Succinate group, which only received parenteral succinate; Sepsis group; and Sepsis which received parenteral succinate. Systemic ROS are measured 24 hours after the procedure. Rats subjected to cecal puncture treated with succinate had less systemic ROS than Septic untreated rats (p=0.007), while there were no differences in creatinine levels (p=0.07). There was no correlation between creatinine and systemic ROS levels (p=0.3). We concluded that parenteral succinate reduces ROS levels, but it does not reduce creatinine levels. Since there is no correlation between both levels, the processes would not be related.

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Pleurotus albidus Modulates Mitochondrial Metabolism Disrupted by Hyperglycaemia in EA.hy926 Endothelial Cells

BioMed Research International ◽

10.1155/2018/2859787 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Gabriela Gambato ◽

Elisa Maria Pavão ◽

Gabriela Chilanti ◽

Roselei Claudete Fontana ◽

Mirian Salvador ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Mitochondrial Dysfunction ◽

Complex I ◽

Electron Transport Chain ◽

Mitochondrial Disorder ◽

Antioxidant Enzyme Activities ◽

Ros Production ◽

Oxygen Species ◽

Transport Chain

Hyperglycaemia exacerbates the production of reactive oxygen species (ROS), contributing to the multiple complications associated with diabetes. Mitochondrial dysfunction is also known to be associated with diabetes. Therefore, the aim of this work was to study the effect of Pleurotus albidus extract on the mitochondrial dysfunction induced by hyperglycaemia in EA.hy926 endothelial cells. The results showed that P. albidus treatment prevented the increase in the activity of complex I of the electron transport chain and minimized the ROS production induced by hyperglycaemia. In addition, the extract minimized oxidative damage to lipids and proteins, caused an imbalance in the antioxidant enzyme activities of superoxide dismutase and catalase, and decreased the nitric oxide levels induced by hyperglycaemia. These data contribute to our understanding of the mitochondrial disorder induced by hyperglycaemia as well as establishing the conditions required to minimize these alterations.

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Ischemic defects in the electron transport chain increase the production of reactive oxygen species from isolated rat heart mitochondria

AJP Cell Physiology ◽

10.1152/ajpcell.00211.2007 ◽

2008 ◽

Vol 294 (2) ◽

pp. C460-C466 ◽

Cited By ~ 199

Author(s):

Qun Chen ◽

Shadi Moghaddas ◽

Charles L. Hoppel ◽

Edward J. Lesnefsky

Keyword(s):

Electron Transport ◽

Complex I ◽

Electron Transport Chain ◽

Myocardial Injury ◽

Complex Iii ◽

Ischemic Damage ◽

Ros Production ◽

Oxygen Species ◽

Net Production ◽

Transport Chain

Cardiac ischemia decreases complex III activity, cytochrome c content, and respiration through cytochrome oxidase in subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). The reversible blockade of electron transport with amobarbital during ischemia protects mitochondrial respiration and decreases myocardial injury during reperfusion. These findings support that mitochondrial damage occurs during ischemia and contributes to myocardial injury during reperfusion. The current study addressed whether ischemic damage to the electron transport chain (ETC) increased the net production of reactive oxygen species (ROS) from mitochondria. SSM and IFM were isolated from 6-mo-old Fisher 344 rat hearts following 25 min global ischemia or following 40 min of perfusion alone as controls. H2O2release from SSM and IFM was measured using the amplex red assay. With glutamate as a complex I substrate, the net production of H2O2was increased by 178 ± 14% and 179 ± 17% in SSM and IFM ( n = 9), respectively, following ischemia compared with controls ( n = 8). With succinate as substrate in the presence of rotenone, H2O2increased by 272 ± 22% and 171 ± 21% in SSM and IFM, respectively, after ischemia. Inhibitors of electron transport were used to assess maximal ROS production. Inhibition of complex I with rotenone increased H2O2production by 179 ± 24% and 155 ± 14% in SSM and IFM, respectively, following ischemia. Ischemia also increased the antimycin A-stimulated production of H2O2from complex III. Thus ischemic damage to the ETC increased both the capacity and the net production of H2O2from complex I and complex III and sets the stage for an increase in ROS production during reperfusion as a mechanism of cardiac injury.

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Regulation of Tumor Necrosis Factor-Induced, Mitochondria- and Reactive Oxygen Species-Dependent Cell Death by the Electron Flux through the Electron Transport Chain Complex I

Antioxidants and Redox Signaling ◽

10.1089/ars.1999.1.3-285 ◽

1999 ◽

Vol 1 (3) ◽

pp. 285-295 ◽

Cited By ~ 60

Author(s):

Vera Goossens ◽

Geert Stangé ◽

Kathleen Moens ◽

Daniel Pipeleers ◽

Johan Grooten

Keyword(s):

Reactive Oxygen Species ◽

Complex I ◽

Electron Transport Chain ◽

Tumor Necrosis ◽

Electron Flux ◽

Chain Complex ◽

Oxygen Species ◽

Transport Chain ◽

Dependent Cell ◽

Necrosis Factor

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The Effects of Montelukast on Antioxidant Enzymes and Proinflammatory Cytokines on the Heart, Liver, Lungs, and Kidneys in a Rat Model of Cecal Ligation and Puncture–Induced Sepsis

The Scientific World JOURNAL ◽

10.1100/tsw.2011.122 ◽

2011 ◽

Vol 11 ◽

pp. 1341-1356 ◽

Cited By ~ 40

Author(s):

Ali Kagan Coskun ◽

Murat Yigiter ◽

Akgun Oral ◽

Fehmi Odabasoglu ◽

Zekai Halici ◽

...

Keyword(s):

Tissue Injury ◽

Cecal Ligation ◽

Lipid Peroxide ◽

Multiple Organ ◽

Control Group ◽

Myeloperoxidase Activity ◽

Protective Effects ◽

Cecal Ligation And Puncture ◽

Necrosis Factor Alpha ◽

Liver And Kidney

We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

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Opening mitoKATP increases superoxide generation from complex I of the electron transport chain

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00272.2006 ◽

2006 ◽

Vol 291 (5) ◽

pp. H2067-H2074 ◽

Cited By ~ 145

Author(s):

Anastasia Andrukhiv ◽

Alexandre D. Costa ◽

Ian C. West ◽

Keith D. Garlid

Keyword(s):

Electron Transport ◽

Complex I ◽

Electron Transport Chain ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Liver Mitochondria ◽

Isolated Rat Heart ◽

Nadh:Ubiquinone Oxidoreductase ◽

Ros Production ◽

Transport Chain

Opening the mitochondrial ATP-sensitive K+ channel (mitoKATP) increases levels of reactive oxygen species (ROS) in cardiomyocytes. This increase in ROS is necessary for cardioprotection against ischemia-reperfusion injury; however, the mechanism of mitoKATP-dependent stimulation of ROS production is unknown. We examined ROS production in suspensions of isolated rat heart and liver mitochondria, using fluorescent probes that are sensitive to hydrogen peroxide. When mitochondria were treated with the KATP channel openers diazoxide or cromakalim, their ROS production increased by 40–50%, and this effect was blocked by 5-hydroxydecanoate. ROS production exhibited a biphasic dependence on valinomycin concentration, with peak production occurring at valinomycin concentrations that catalyze about the same K+ influx as KATP channel openers. ROS production decreased with higher concentrations of valinomycin and with all concentrations of a classical protonophoretic uncoupler. Our studies show that the increase in ROS is due specifically to K+ influx into the matrix and is mediated by the attendant matrix alkalinization. Myxothiazol stimulated mitoKATP-dependent ROS production, whereas rotenone had no effect. This indicates that the superoxide originates in complex I (NADH:ubiquinone oxidoreductase) of the electron transport chain.

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Parenteral Succinate Reduces Levels of Reactive Oxygen Species, but It Does Not Reduce Caspase-3 Serum and Tissue Levels.

10.21203/rs.3.rs-502147/v1 ◽

2021 ◽

Author(s):

Sebastián Pablo Chapela ◽

Giovanna Muscogiuri ◽

Luigi Barrea ◽

Evelyn Frias-Toral ◽

Hilda Burgos ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Caspase 3 ◽

Cecal Ligation ◽

Krebs Cycle ◽

Reactive Oxygen ◽

Sepsis Group ◽

Control Group ◽

Oxygen Species ◽

Sprague Dawley ◽

Tissue Levels

Abstract Purpose: In sepsis Reactive Oxygen Species (ROS) production and apoptosis are two physiopathological processes that are increased. Succinate is a Krebs cycle intermediate that is reduced in Complex II of the mitochondria. This work aims to determine if succinate administration to septic rats improves serum ROS levels and serum and tissue levels of apoptosis. Methods: Sepsis was induced with cecal ligation and puncture in 200gr Sprague Dawley rats. 4 groups were formed (control, succinate, sepsis, and sepsis + succinate). 5mml/kg of intraperitoneal succinate were administered to the succinate and sepsis + succinate groups 2 h before sepsis induction and 2 h before sample taking. ROS levels were measured with dichlorofluorescein-diacetate, and apoptosis was measured with a Caspase-3 ELISA kit. Results: There were significant differences in serum ROS levels between the control group and the sepsis group (P = 0.012), but there were no differences in serum Caspase-3 levels (P = 0.15). The succinate administration reduced serum ROS levels in the sepsis + succinate group compared with the sepsis group in a statistically significant way (P = 0.004), but it did not reduce serum Caspase-3 levels (P = 0.39). There were no differences between groups in kidney and liver Caspase-3 levels. There was no correlation between serum ROS levels and serum Caspase-3 levels. Conclusions: In this model, ROS levels were reduced with succinate infusion, but Caspase-3 levels were not. In addition, ROS levels and apoptosis levels are not correlated, which suggests that those processes occur at different times.

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Somatic production of reactive oxygen species does not predict its production in sperm cells across Drosophila melanogaster lines

BMC Research Notes ◽

10.1186/s13104-021-05550-7 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Biz R. Turnell ◽

Luisa Kumpitsch ◽

Anne-Cécile Ribou ◽

Klaus Reinhardt

Keyword(s):

Reactive Oxygen Species ◽

Drosophila Melanogaster ◽

Reactive Oxygen ◽

Future Research ◽

Ros Production ◽

Oxygen Species ◽

Loss Of Function ◽

Wild Type ◽

Ros Scavenging ◽

Transport Chain

Abstract Objective Sperm ageing has major evolutionary implications but has received comparatively little attention. Ageing in sperm and other cells is driven largely by oxidative damage from reactive oxygen species (ROS) generated by the mitochondria. Rates of organismal ageing differ across species and are theorized to be linked to somatic ROS levels. However, it is unknown whether sperm ageing rates are correlated with organismal ageing rates. Here, we investigate this question by comparing sperm ROS production in four lines of Drosophila melanogaster that have previously been shown to differ in somatic mitochondrial ROS production, including two commonly used wild-type lines and two lines with genetic modifications standardly used in ageing research. Results Somatic ROS production was previously shown to be lower in wild-type Oregon-R than in wild-type Dahomey flies; decreased by the expression of alternative oxidase (AOX), a protein that shortens the electron transport chain; and increased by a loss-of-function mutation in dj-1β, a gene involved in ROS scavenging. Contrary to predictions, we found no differences among these four lines in the rate of sperm ROS production. We discuss the implications of our results, the limitations of our study, and possible directions for future research.

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