Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine

2002 ◽  
Vol 283 (4) ◽  
pp. H1634-H1644 ◽  
Author(s):  
Paul D. Mongan ◽  
John Capacchione ◽  
Shanda West ◽  
John Karaian ◽  
Dawn Dubois ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Redox State ◽  
Redox Status ◽  
Sodium Pyruvate ◽  
Beneficial Effects ◽  
Redox Environment ◽  
Arterial Concentration ◽  
Arterial Hemorrhage ◽  
Hemorrhage Volume ◽  
Pyruvate Ratio

Previous studies have shown that the liver is the first organ to display signs of injury during hemorrhagic shock. We examined the mechanism by which pyruvate can prevent liver damage during hemorrhagic shock in swine anesthetized with halothane. Thirty minutes after the induction of a 240-min controlled arterial hemorrhage targeted at 40 mmHg, hypertonic sodium pyruvate (0.5 g · kg−1 · h−1) was infused to achieve an arterial concentration of 5 mM. The volume and osmolality effects of pyruvate were matched with 10% saline (HTS) and 0.9% saline (NS). Although the peak hemorrhage volume increased significantly in both the pyruvate and HTS group, only the pyruvate treatment was effective in delaying cardiovascular decompensation. In addition, pyruvate effectively maintained the NADH/NAD redox state, as evidenced by increased microdialysate pyruvate levels and a significantly lower lactate-to-pyruvate ratio. Pyruvate also prevented the loss of intracellular antioxidants (GSH) and a reduction in the GSH-to-GSSG ratio. These beneficial effects on the redox environment decreased hepatic cellular death by apoptosis. Pyruvate significantly increased the ratio of Bcl-Xl (antiapoptotic molecule)/Bax (proapoptotic molecule), prevented the release of cytochrome c from mitochondria, and decreased the fragmentation of caspase 3 and poly(ADP ribose) polymerase (DNA repair enzyme). These beneficial findings indicate that pyruvate infused 30 min after the onset of severe hemorrhagic shock is effective in maintaining the redox environment, preventing the loss of the key antioxidant GSH, and decreasing early apoptosis indicators.

scholarly journals Intravenous pyruvate prolongs survival during hemorrhagic shock in swine

1999 ◽  
Vol 277 (6) ◽  
pp. H2253-H2263 ◽  
Author(s):  
Paul D. Mongan ◽  
John L. Fontana ◽  
Rouyan Chen ◽  
Rolf Bünger
Keyword(s):  
Hemorrhagic Shock ◽  
Redox State ◽  
Energy State ◽  
Time To Peak ◽  
Sagittal Sinus ◽  
Cerebrovascular Function ◽  
Arterial Hemorrhage ◽  
Hemorrhage Volume ◽  
Pyruvate Ratio

Pyruvate improves cellular and organ function during hypoxia and ischemia and stabilizes the NADH redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on cardiovascular and neocortical function, indexes of the cytosolic redox state (lactate/pyruvate ratio, L/P) and cellular energy state (adenosine and degradative products hypoxanthine and inosine, ADO + HX + Ino) during controlled arterial hemorrhage (40 mmHg) in sedated swine (45 kg). Na+ pyruvate was infused 1 h before (1 g ⋅ kg−1 ⋅ h−1) and 2 h during (0.5 g ⋅ kg−1 ⋅ h−1) hemorrhage to attain arterial pyruvate levels of 6 mM. Volume (0.9% NaCl) and osmotic (10% NaCl) effects were matched in controls. Time to peak hemorrhage (57 min) and peak hemorrhage volume (43 ml/kg) were similar in all groups. The volume and osmotic groups experienced spontaneous cardiovascular decompensation between 60 and 90 min, with an average time until death of 82.7 ± 5.5 and 74.8 ± 8.2 min. In contrast, survival in the pyruvate group was 151.2 ± 10.0 min ( P < 0.001). During hemorrhage, the pyruvate group had better cardiovascular and cerebrovascular function with significantly higher systemic and cerebral oxygen consumption and less attenuation of the amplitude and frequency of the electrocorticogram. In addition, pyruvate prevented metabolic acidosis and stabilized the L/P. Pyruvate slowed the rise in neocortical microdialysis levels of ADO + HX + Ino, and prevented the net efflux of ADO + HX + Ino into the sagittal sinus. The findings reveal considerable metabolic and functional enhancement by pyruvate during severe hemorrhagic shock with a 75-min delay in spontaneous cardiovascular decompensation and death.

Pyruvate improves cerebral metabolism during hemorrhagic shock

2001 ◽  
Vol 281 (2) ◽  
pp. H854-H864 ◽  
Author(s):  
Paul D. Mongan ◽  
John Capacchione ◽  
John L. Fontana ◽  
Shanda West ◽  
Rolf Bünger
Keyword(s):  
Hemorrhagic Shock ◽  
Redox State ◽  
Cerebral Metabolism ◽  
Energy State ◽  
Time To Peak ◽  
Arterial Hemorrhage ◽  
Hemorrhage Volume ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
And Function

Pyruvate (PYR) improves cellular and organ function hypoxia and ischemia by stabilizing the reduced nicotinamide adenine dinucleotide redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on neocortical function, indexes of the cytosolic redox state, cellular energy state, and ischemia during a prolonged (4 h) controlled arterial hemorrhage (40 mmHg) in swine. Thirty minutes after the onset of hemorrhagic shock, sodium PYR ( n = 8) was infused (0.5 g · kg−1 · h−1) to attain arterial levels of 5 mM. The volume and osmotic effects were matched with 10% NaCl [hypertonic saline (HTS)] ( n = 8) or 0.9% NaCl [normal saline (NS)] ( n = 8). During the hemorrhage protocol, the time to peak hemorrhage volume was significantly delayed in the PYR group compared with the HTS and NS groups (94 ± 5 vs. 73 ± 6 and 72 ± 4 min, P < 0.05). In addition to the early onset of the decompensatory phase of hemorrhagic shock, the complete return of the hemorrhage volume during decompensatory shock resulted in the death of five and four animals, respectively, in the HTS and NS groups. In contrast, in the PYR group, reinfusion of the hemorrhage volume was slower and all animals survived the 4-h hemorrhage protocol. During hemorrhage, the PYR group also exhibited improved cerebral cortical metabolic and function status. PYR slowed and reduced the rise in neocortical microdialysis levels of adenosine, inosine, and hypoxanthine and delayed the loss of cerebral cortical biopsy ATP and phosphocreatine content. This improvement in energetic status was evident in the improved preservation of the electrocorticogram in the PYR group. PYR also prevented the eightfold increase in the excitotoxic amino acid glutamate observed in the HTS group. The findings show that PYR administered after the onset of hemorrhagic shock markedly improves cerebral metabolic and functional status for at least 4 h.

scholarly journals Imaging NAD(H) Redox Alterations in Cryopreserved Alveolar Macrophages from Ozone-Exposed Mice and the Impact of Nutrient Starvation during Long Lag Times

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 767
Author(s):  
He N. Xu ◽  
Joanna Floros ◽  
Lin Z. Li ◽  
Shaili Amatya
Keyword(s):  
Oxidative Stress ◽  
Alveolar Macrophages ◽  
Redox State ◽  
Redox Status ◽  
Nutrient Starvation ◽  
Ozone Exposure ◽  
Reduced Form ◽  
Time Period ◽  
Lag Times ◽  
The Impact

Employing the optical redox imaging technique, we previously identified a significant redox shift of nicotinamide adenine dinucleotide (NAD and the reduced form NADH) in freshly isolated alveolar macrophages (AM) from ozone-exposed mice. The goal here was twofold: (a) to determine the NAD(H) redox shift in cryopreserved AM isolated from ozone-exposed mice and (b) to investigate whether there is a difference in the redox status between cryopreserved and freshly isolated AM. We found: (i) AM from ozone-exposed mice were in a more oxidized redox state compared to that from filtered air (FA)-exposed mice, consistent with the results obtained from freshly isolated mouse AM; (ii) under FA exposure, there was no significant NAD(H) redox difference between fresh AM that had been placed on ice for 2.5 h and cryopreserved AM; however, under ozone exposure, fresh AM were more oxidized than cryopreserved AM; (iii) via the use of nutrient starvation and replenishment and H2O2-induced oxidative stress of an AM cell line, we showed that this redox difference between cryopreserved and freshly isolated AM is likely the result of the double “hit”, i.e., the ozone-induced oxidative stress plus nutrient starvation that prevented freshly isolated AM from a full recovery after being on ice for a prolonged time period. The cryopreservation technique we developed eliminates/minimizes the effects of oxidative stress and nutrient starvation on cells. This method can be adopted to preserve lung macrophages from animal models or clinical patients for further investigations.

scholarly journals The Effectiveness of Glutathione Redox Status as a Possible Tumor Marker in Colorectal Cancer

2021 ◽  
Vol 22 (12) ◽  
pp. 6183
Author(s):  
Delia Acevedo-León ◽  
Lidia Monzó-Beltrán ◽  
Segundo Ángel Gómez-Abril ◽  
Nuria Estañ-Capell ◽  
Natalia Camarasa-Lillo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Redox State ◽  
Reduced Glutathione ◽  
Redox Status ◽  
Oxidation Products ◽  
Interventional Study ◽  
Thiol Redox State ◽  
Thiol Redox ◽  
Glutathione Redox

The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.

scholarly journals Regulatory redox state in tree seeds

2017 ◽  
Vol 86 (4) ◽  
Author(s):  
Ewelina Ratajczak ◽  
Karl Josef Dietz
Keyword(s):  
Redox State ◽  
Redox Status ◽  
Long Term Storage ◽  
Tree Seeds ◽  
Term Storage ◽  
Intermediate Seeds

Peroxiredoxins (Prx) are important regulators of the redox status of tree seeds during maturation and long-term storage. Thioredoxins (Trx) are redox transmitters and thereby regulate Prx activity. Current research is focused on the association of Trx with Prx in tree seeds differing in the tolerance to desiccation. The results will allow for better understanding the regulation of the redox status in orthodox, recalcitrant, and intermediate seeds. The findings will also elucidate the role of the redox status during the loss of viability of sensitive seeds during drying and long-term storage.

scholarly journals Blood redox state and survival in patients with rectal cancer

2015 ◽  
Vol 17 (4) ◽  
Author(s):  
A. P. Burlaka ◽  
V. V. Holotyuk ◽  
A. V. Vovk ◽  
S. M. Lukin ◽  
Ye. P. Sydoryk
Keyword(s):  
Rectal Cancer ◽  
Redox State ◽  
Venous Blood ◽  
Reference Sample ◽  
Redox Status ◽  
Paramagnetic Resonance ◽  
Blood Samples ◽  
Cell Functions ◽  
Electron Paramagnetic ◽  
Concentration Of Electrons

<p>The cells of an organism have a definite concentration of electrons that characterizes their stable redox status. Electrons are transported to the oxygen and create the potential energy to realize the cell functions such as growth<br />and apoptosis. Imbalance in the redox state of cells initiates the development and progression of the most socially significant pathologies. The aim of the research was to study the blood redox state in patients with rectal cancer (RC ) (the levels of ceruloplasmin (CP), transferrin (TF) and “free iron” (“FI”), superoxyd-, NO-generating activity of neutrophils and platelets) and its impact on оverall survival (ОS ). Venous blood samples of 60 patients with RC (T2-4N0-2M0G2) and 20 donors were studied. The defining levels of CP, TF, “FI” in blood was performed by electron paramagnetic resonance (EPR) at the temperature of liquid nitrogen (T=77 K ). The blood redox state in patients with RC are formed by: 2 times reduced CP activity in comparison with the<br />reference sample; 3 times reduced TF content and 10 times increased “FI” levels; slightly increased superoxide generating activity of neutrophils and 8–14 times increased superoxide generating activity of platelets; 3.7 and 4.3 times reduced NO generation rate of neutrophils and platelets, respectively. It was found that the survival in patients with RC was significantly influenced by the level of CP activity (p&lt;0.044), levels of “FI” (p&lt;0.026), superoxide generating activity of NADP·H-oxidase of neutrophils (p&lt;0.043). It was found that the adenocarcinoma progression in patients with RC (T2-4N0-2M0G2) was ccompanied bychange in the blood redox state by reducing CP activity and level of TF that led to the emergence of “FI” and the increase of its level. Besides, the changes of superoxyde- and NO-generating activity NADP∙H-oxidase and iNOS of neutrophils and platelets significantly influenced the imbalance of the blood redox state in the patients. The state of redox forming blood components in patients correlated with the оverall 5-year survival. It was found that the CP</p><p>activity, the “FI” level and the superoxide-generating activity of NADP·H-xidase of neutrophils and platelets hadsignificant effect on ОS .</p>

RELATIONS OF INTRACELLULAR IONS TO METABOLITE SEQUENCES IN MUSCLE IN KWASHIORKOR

PEDIATRICS ◽  
1960 ◽  
Vol 26 (6) ◽  
pp. 960-972
Author(s):  
Jack Metcoff ◽  
Silvestre Frenk ◽  
Irena Antonowicz ◽  
Gustavo Gordillo ◽  
Elizabeth Lopez
Keyword(s):  
Citric Acid Cycle ◽  
Potassium Phosphate ◽  
Sodium Pyruvate ◽  
Intracellular Electrolytes ◽  
Intermediary Metabolite ◽  
Time Of Admission ◽  
Intracellular Ions ◽  
Potassium Magnesium ◽  
Pyruvate Ratio ◽  
Cellular Swelling

A biopsy was obtained at the time of admission and subsequently from eight children with severe kwashiorkor. The biopsies were analyzed for electrolyte content and for the quantities of certain intermediates (pyruvate, lactate, citrate and alphaketoglutarate). The results in five children who recovered are compared with those from three children who died. Significant reductions occurred in intracellular potassium, phosphate, magnesium and pyruvate, but lactate and alpha-ketoglutarate were increased. When the intracellular electrolytes were related to a specific intermediary metabolite (on the premise that the ion served as an activator or inhibitor in an enzymatic sequence leading to the production or the utilization of that intermediate) the changes assumed greater significance. A more dynamic interpretation of the data was provided by comparing ion:metabolite ratios of the initial with those of the second biopsy in patients who either recovered or died. Death from kwashiorkor was associated with a marked reversal in the sodium: pyruvate ratio and the apparent inorganic and organic phosphate to pyruvate ratios within the cell. These changes are consistent with some defect in the formation of pyruvate from phosphoenolpyruvate in a potassium-, magnesium-, phosphorus-dependent system. The citrate, magnesium and "true" inorganic phosphate to alphaketoglutarate ratios also were reversed in children who died compared to those who recovered. Such changes indicate a possible inhibition in the usual citric acid cycle pathway along which alpha-ketoglutarate is metabolized. Preliminary data on concentrations of phosphoenolpyruvate, isocitrate and oxalacetate within the muscle cell and on the activities of pyruvic kinase also are presented. The data are consistent with the hypothesis that the cellular swelling (in muscle) often characteristic of kwashiorkor leads to reduction in concentration of essential intracellular ions with inhibition of intermediary energy metabolism, thus leading to death. Since intracellular ions may function as activators or inhibitors for specific enzymes, it is suggested that changing quantities of a particular ion may be referred to the quantity of metabolite forming substrate or product of the specific enzymatic sequence. Altered ratios of ions to appropriate metabolites emphasize the possible significance of intracellular electrolytes in the biological system.

Considerations of the importance of redox state for reactive nitrogen species action

2019 ◽  
Vol 70 (17) ◽  
pp. 4323-4331 ◽  
Author(s):  
John T Hancock
Keyword(s):  
Reactive Nitrogen Species ◽  
Redox State ◽  
Physiological Responses ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Signalling Molecules ◽  
Redox Environment ◽  
A Cell ◽  
Redox Poise ◽  
Intracellular Redox

Abstract Nitric oxide (NO) and other reactive nitrogen species (RNS) are immensely important signalling molecules in plants, being involved in a range of physiological responses. However, the exact way in which NO fits into signal transduction pathways is not always easy to understand. Here, some of the issues that should be considered are discussed. This includes how NO may interact directly with other reactive signals, such as reactive oxygen and sulfur species, how NO metabolism is almost certainly compartmentalized, that threshold levels of RNS may need to be reached to have effects, and how the intracellular redox environment may impact on NO signalling. Until better tools are available to understand how NO is generated in cells, where it accumulates, and to what levels it reaches, it will be hard to get a full understanding of NO signalling. The interaction of RNS metabolism with the intracellular redox environment needs further investigation. A changing redox poise will impact on whether RNS species can thrive in or around cells. Such mechanisms will determine whether specific RNS can indeed control the responses needed by a cell.

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